KR20210108423A - 아데노 관련 바이러스 (aav) 생산자 세포주 및 관련 방법 - Google Patents

아데노 관련 바이러스 (aav) 생산자 세포주 및 관련 방법 Download PDF

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KR20210108423A
KR20210108423A KR1020217022728A KR20217022728A KR20210108423A KR 20210108423 A KR20210108423 A KR 20210108423A KR 1020217022728 A KR1020217022728 A KR 1020217022728A KR 20217022728 A KR20217022728 A KR 20217022728A KR 20210108423 A KR20210108423 A KR 20210108423A
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빙난 구
케이틀린 엠. 겐터
아난디타 세스
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론자 워커스빌 아이엔씨.
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Abstract

본 개시내용은 탈억제 가능한 프로모터의 제어하에, 헬퍼 유전자 및 AAV 유전자를 암호화하는 핵산을 적절하게 포함하는, 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포주에 관한 것이다. 본 개시내용은 또한 이러한 유전자를 암호화하는 단리된 핵산 분자, 뿐만 아니라 AAV를 생산하기 위해 포유동물 세포를 사용하는 방법에 관한 것이다.

Description

아데노 관련 바이러스 (AAV) 생산자 세포주 및 관련 방법
본 개시내용은 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포주에 관한 것이다. 세포는 탈억제 가능한 프로모터의 제어하에, 헬퍼 유전자 및 AAV 유전자를 암호화하는 핵산을 적절하게 포함한다. 본 개시내용은 또한 이러한 유전자를 암호화하는 단리된 핵산 분자, 뿐만 아니라 AAV를 생산하기 위해 포유동물 세포를 사용하는 방법에 관한 것이다.
서열 목록
본 출원은 ASCII 형식으로 전자적으로 제출되고 그 전문이 본원에 참고로 포함된 서열 목록을 포함한다. 2019년 12월 17일 생성된, 상기 ASCII 사본은 0132-0049WO1_SL.txt로 명명되고 364,567　바이트 크기이다.
안전성 프로파일 및 장기 발현 능력은 아데노 관련 바이러스 (AAV)를 인간에서 유전자 치료법을 위한 우수한 바이러스 벡터가 되게 한다. 야생형 AAV 게놈은 바이러스 복제 및 패키징을 위한 역위 말단 반복 (ITR)이 측면에 있는, 복제를 위한 조절 유전자 (Rep) 및 캡시드를 위한 구조 유전자 (Cap)를 포함하는 4.7 kb 단일 가닥 DNA로 구성된다. 종속 바이러스로서, 숙주 세포에서 AAV 복제는 헬퍼 바이러스, 예를 들어 아데노바이러스 (Ad) 및 단순 헤르페스 바이러스의 동시감염을 필요로 한다. 대안적으로, 복제된 헬퍼 유전자의 발현은 또한 AAV 복제를 지원할 수 있다. 예를 들어, 재조합 AAV는 세 가지 플라스미드의 공동 형질감염에 의해 HEK293 세포에서 생산될 수 있다: 아데노바이러스로부터의 E2A, E4Orf6 및 VA를 발현하는 pHelper 플라스미드, Rep 및 Cap 단백질에 대한 pRep-Cap 플라스미드, 및 원하는 관심 유전자 (GOI)를 운반하는 AAV 전달 플라스미드.
현재, AAV 제조는 여러 가교 플랫폼에 의존한다. 상술한 HEK293 세포에서의 삼중 감염 이외에, AAV는 곤충 세포로의 각각, Rep-Cap 및 GOI를 발현하는 2개의 바큘로바이러스의 동시감염에 의해 생산될 수 있다. 그러나, 이들 바큘로바이러스는 더 높은 계대에서 불안정하고 제조하는 데 시간이 많이 소비된다 (예를 들어, Urabe et al., " Insect Cells as a Factory to Produce Adeno-Associated Virus Type 2 Vectors," Human Gene Therapy 13:1935-1943 (2002) 참조). 안정적으로 통합된 Rep-Cap 및 GOI를 갖는 HeLa 패키징 세포가 또한 개발되어 있다. 그럼에도 불구하고, 이들 시스템은 여전히 야생형 아데노바이러스를 헬퍼 바이러스로서 필요로 하고, AAV 생성물에서 복제형 아데노바이러스의 오염의 위험이 있다 (예를 들어, Robert et al., " Manufacturing of recombinant adeno-associated viruses using mammalian expression platforms," Biotechnology Journal 12:1600193 (1-16) (2017) 참조.
오염을 제한하고 비용을 감소시키면서, 재현 가능하고 안정한 결과를 제공하기 위해, 대량 생산으로 용이하게 확장 가능한 AAV의 생산을 위한 세포주 및 관련 방법이 필요하다.
일부 구현예에서, 제1 탈억제 가능한 프로모터의 제어하에 바이러스 헬퍼 유전자를 암호화하는 핵산 분자, 제2 탈억제 가능한 프로모터의 제어하에 AAV 유전자를 암호화하는 핵산 분자, 및 제1 및 제2 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 핵산 분자를 포함하는, 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포가 본원에서 제공된다.
추가 구현예에서, 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 핵산 분자를 포함하는, 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포가 본원에서 제공된다.
추가 구현예에서, 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 단리된 핵산 분자가 본원에서 제공된다.
또 다른 추가 구현예에서, 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 단리된 핵산 분자로 형질 감염시키고, 포유동물 세포를 억제자 요소의 결합 파트너로 처리하고, 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화시키고, AAV를 생산하고, 그리고 AAV를 수확하는 것을 포함하는 포유동물 세포에서 아데노 관련 바이러스 (AAV)를 생산하는 방법이 본원에서 제공된다.
추가 구현예에서, 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 단리된 핵산 분자로 형질 감염시키고, 포유동물 세포를 억제자 요소의 결합 파트너로 처리하고, 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화하고, AAV를 생산하고, AAV를 수확하고 포유동물 환자에 AAV를 투여하는 것을 포함하는 아데노 관련 바이러스 (AAV)를 사용하는 치료 방법이 본원에서 제공된다.
또 다른 추가 구현예에서, TetR 및/또는 TetR-KRAB을 암호화하는 하나 이상의 핵산을 안정적으로 발현하는 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에 E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산, 제2 탈억제 가능한 프로모터의 제어하에 AAV 유전자를 포함하는 Rep 및 Cap 유전자를 암호화하는 제2 핵산, 및, 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산으로 형질 감염시키고, 포유동물 세포를 TetR 및/또는 TetR-KRAB의 결합 파트너로 처리하고, 제1, 제2, 및 제3 탈억제 가능한 프로모터를 활성화시키고, AAV를 생산하고, AAV를 수확하는 것을 포함하는 아데노 관련 바이러스 (AAV)를 생산하는 방법이 본원에서 제공된다.
또 다른 추가 구현예에서, 포유동물 세포를 TetR 및/또는 TetR-KRAB 억제자, TetR 및/또는 TetR-KRAB 억제자 측면에 있는 닭 과민성 부위-4 (cHS4) 서열, 및 선별 유전자를 암호화하는 핵산으로 안정적으로 형질 감염시키고, 안정적으로 형질감염된 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에, E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산; 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자를 암호화하는 제2 핵산; 및 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산으로 형질 감염시키고; 포유동물 세포를 TetR의 결합 파트너로 처리하고; 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화시키고; AAV를 생산하고; 그리고 AAV를 수확하는 것을 포함하는 아데노 관련 바이러스 (AAV)를 생산하는 방법이 본원에서 제공된다.
도 1은 본원의 구현예에 따른 헬퍼 및 VA 유전자의 발현을 제어하기 위한 탈억제 가능한 프로모터의 사용의 개략도를 나타낸다.
도 2a 및 2b는 본원의 구현예에 따른 헬퍼 및 VA 유전자의 생산을 위한 예시적인 핵산 분자를 나타낸다.
도 3은 본원의 구현예에 따른 헬퍼 및 AAV 유전자의 유도 결과를 나타낸다.
도 4a-4c는 본원의 구현예에 따른 AAV 유전자의 발현을 위한 탈억제 가능한 작제물의 개략도를 나타낸다.
도 5는 본원의 구현예에 따른 예시적인 탈억제 가능한 p5 프로모터를 나타낸다.
도 6은 본원의 구현예에 따른 예시적인 탈억제 가능한 p19 프로모터를 나타낸다.
도 7a-7b는 본원의 구현예에 따른, 인공 인트론을 포함하는 예시적인 탈억제 가능한 p19 프로모터를 나타낸다.
도 8a-8b는 본원의 구현예에 따른, Rep-Cap 벡터를 사용하는 Rep-Cap 발현 및 AAV 역가의 결과를 나타낸다.
도 9a-9b는 본원의 구현예에 따른, 헬퍼 및 Rep-Cap 벡터를 사용하는 Rep-Cap 발현 및 AAV 역가의 추가 결과를 나타낸다.
도 10a-10d는 본원의 구현예에 따른, 헬퍼, AAV 및 VA 유전자를 암호화하는 예시적인 핵산 작제물을 나타낸다.
도 11a-11e는 본원의 구현예에 따른, 헬퍼, AAV, 관심 유전자, 및 Rep-Cap 벡터를 암호화하는 예시적인 핵산 작제물을 나타낸다.
도 12a-12b는 본원의 구현예에 따른, TetR 및 TetR-KRAB을 암호화하는 예시적인 핵산 작제물을 나타낸다.
청구범위 및/또는 명세서에서 용어 "포함하는"과 함께 사용될 때 "a" 또는 "an"의 사용은 "하나"를 의미할 수 있지만, 이는 또한 "하나 이상," "적어도 하나," 및 "하나 또는 하나 이상"의 의미와 일치한다.
본 출원에 걸쳐, 용어 "약"은 값이 값을 결정하기 위해 사용되는 방법/장치의 오류의 고유 변이를 포함하는 것을 나타내기 위해 사용된다. 일반적으로 용어는 상황에 따라 대략 또는 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% 또는 20% 미만 변동성을 포함하는 것을 의미한다.
본 개시내용은 대안만 및 "및/또는"을 지칭하는 정의를 지원하지만, 대안만을 언급하도록 명시적으로 표시되지 않거나 대안이 상호 배타적인 경우가 아닌 한 청구범위에서 용어 "또는"의 사용은 "및/또는"을 의미하는 것으로 사용된다.
본 명세서 및 청구항(들)에서 사용된 바와 같이, 단어 "포함하는" (및 임의의 형태의 포함하는, 예를 들어 "comprise" 및 "comprises"), "갖는" (및 임의의 형태의 갖는, 예를 들어 "have" 및 "has"), "포함하는" (및 임의의 형태의 포함하는, 예를 들어 "includes" 및 "include") 또는 "함유하는" (및 임의의 형태의 함유하는, 예를 들어 "contains" 및 "contain")은 포괄적이거나 개방형이며 추가, 인용되지 않은 요소 또는 방법 단계를 배제하지 않는다. 본 명세서에서 논의된 임의의 구현예는 본 발명의 임의의 방법, 시스템, 숙주 세포, 발현 벡터, 및/또는 조성물과 관련하여 구현될 수 있음이 고려된다. 더욱이, 본 발명의 조성물, 시스템, 세포, 및/또는 핵산은 본원에 기술된 임의의 방법을 달성하기 위해 사용될 수 있다.
아데노 관련 바이러스 (AAV)는 전 세계적으로 120개 이상의 임상 시험에서 유전자 요법에 대한 선택의 벡터로 떠오르고 있다. 재조합 AAV의 빠르게 증가하는 수요는 매우 효율적이고 강력한 제조 플랫폼을 필요로 한다. 그러나, 일시적 형질감염 및 헬퍼 바이러스 시스템을 포함하는, AAV 생산을 위한 현재 방법은 비용이 많이 들고 실험실 집약적이다. 상당히 감소된 비용으로 장기 해결책을 위한 효율적인 AAV 제조를 제공하는 플라스미드/헬퍼 바이러스가 없는 AAV 생산자 세포주, 및 이의 사용 방법이 본원에서 기술된다. 본원에 기술된 AAV 생산자 세포주는 임상 및 상업적 AAV 제조를 위한 차세대 플랫폼을 대표한다.
따라서, 구현예에서, 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포가 본원에서 제공된다.
본원에 사용된 바와 같이, 용어 "포유동물 세포"는 예를 들어, 인간 세포, 마우스 세포, 랫트 세포, 원숭이 세포, 햄스터 세포 등과 같은 포유류 목의 임의의 구성원으로부터의 세포를 포함한다. 일부 구현예에서, 세포는 마우스 세포, 인간 세포, 차이니즈 햄스터 난소 (CHO) 세포, CHOK1 세포, CHO-DXB11 세포, CHO-DG44 세포, 모든 변이체를 포함하는 CHOK1SV 세포 (예를 들어 POTELLIGENT®, Lonza, Slough, UK), 모든 변이체를 포함하는 CHOK1SV GS-KO (글루타민 합성효소 녹아웃) 세포 (예를 들어, XCEED™ Lonza, Slough, UK)이다. 예시적인 인간 세포는 인간 배아 신장 (HEK) 세포, 예를 들어 HEK293, HeLa 세포, 또는 HT1080 세포를 포함한다.
포유동물 세포는 부착 배양물 또는 현탁 배양물일 수 있는 포유동물 세포 배양물을 포함한다. 부착 배양물은 기질 표면, 예를 들어 플라스틱 플레이트, 접시 또는 다른 적절한 세포 배양 성장 플랫폼에서 성장하는 세포를 지칭하고, 고정 의존적일 수 있다. 현탁 배양물은 예를 들어, 배양 플라스크 또는 대형 현탁 통에서 유지될 수 있는 세포를 지칭하고, 이는 가스 및 영양소 교환을 위한 넓은 표면적을 허용한다. 현탁 세포 배양은 종종 적절한 혼합을 제공하기 위해 교반 또는 동요 메커니즘을 활용한다. 세포를 현탁 상태로 유지하기 위한 배지 및 조건은 일반적으로 당 업계에 공지되어 있다. 예시적인 현탁 세포 배양물은 인간 HEK293 클론 세포를 포함한다.
본원에 사용된 바와 같이, 용어 "아데노 관련 바이러스 (AAV)"는 파르보바이러스과 및 디펜도파르보바이러스속의 단일 가닥 DNA를 함유하는 소형, 복제-결함 비외피성 바이러스를 지칭한다. 10개 초과의 아데노 관련 바이러스 혈청형이 지금까지 확인되었고, 혈청형 AAV2가 가장 잘 특성화되었다. AAV 혈청형의 다른 비제한적 예시는 ANC80, AAV1, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, 및 AAV11이다. 이들 혈청형 외에도, AAV 위형이 개발되어 있다. AAV 위형은 제1 혈청형의 캡시드 및 제2 혈청형의 게놈을 함유한다 (예를 들어 위형 AAV2/5는 혈청형 AAV2의 게놈 및 AAV5의 캡시드를 갖는 AAV에 해당할 것임).
본원에서 언급된 바와 같이, 용어 "아데노바이러스"는 아데노바이러스과의 이중 가닥 DNA를 함유하는 20면체 뉴클레오캡시드를 갖는 비외피성 바이러스를 지칭한다. 50개 초과의 아데노바이러스 하위유형이 인간으로부터 단리되었고 다수의 추가 하위유형이 다른 포유동물 및 새로부터 단리되었다. 예를 들어, Ishibashi et al., "Adenoviruses of animals," In The Adenoviruses, Ginsberg, ed., Plenum Press, New York, N.Y., pp. 497-562 (1984); Strauss, "Adenovirus infections in humans," In The Adenoviruses, Ginsberg, ed., Plenum Press, New York, N.Y., pp. 451-596 (1984) 참조. 이들 하위유형은 아데노바이러스 과에 속하고, 이는 현재 2개의 속, 즉 포유류 아데노바이러스 및 조류 아데노바이러스로 나뉜다. 모든 아데노바이러스는 형태학적 및 구조적으로 유사하다. 그러나, 인간에서, 아데노바이러스는 다양한 면역학적 특성을 나타내므로, 혈청형으로 나뉜다. 인간 아데노바이러스의 2개의 혈청형, 즉 AV2 및 AV5가 집중적으로 연구되었고 아데노바이러스에 대한 일반적인 정보의 대부분을 제공하였다.
구현예에서, 본원에 제공된 포유동물 세포는 제1 탈억제 가능한 프로모터의 제어하에 바이러스 헬퍼 유전자를 암호화하는 핵산 분자, 제2 탈억제 가능한 프로모터의 제어하에 AAV 유전자를 암호화하는 핵산 분자, 및 제1 및 제2 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 핵산 분자를 적절히 포함한다.
예시적인 구현예에서, AAV를 생산하기 위한 다양한 구성요소를 암호화하는 핵산 분자는 별개의 핵산 분자, 예를 들어 별개의 플라스미드 또는 벡터에서 포유동물 세포 내에 함유된다. 다른 구현예에서, AAV를 생산하기 위한 다양한 구성요소를 암호화하는 핵산 분자는 동일한 플라스미드 또는 벡터에 포함된다. 추가 구현예에서 구성 요소들의 일부가 동일한 핵산 분자 (예를 들어, 헬퍼 유전자 및 AAV 유전자)에 포함되는 동안, 다른 유전자는 별개의 핵산 분자 (예를 들어, 억제자 요소를 암호화하는 유전자)에 포함된다.
"핵산," "핵산 분자," 또는 "올리고뉴클레오티드"는 공유 결합된 뉴클레오티드를 포함하는 중합체 화합물을 의미한다. 용어 "핵산"은 폴리리보핵산 (RNA) 및 폴리디옥시리보핵산 (DNA)을 포함하고, 이들 모두 단일 또는 이중 가닥일 수 있다. DNA는 상보 DNA (cDNA), 게놈 DNA, 플라스미드 또는 벡터 DNA, 및 합성 DNA를 포함하지만, 이에 한정되지 않는다. RNA는 mRNA, tRNA, rRNA, snRNA, 마이크로RNA, miRNA, 또는 MIRNA를 포함하지만, 이에 한정되지 않는다.
본원에 기술된 다양한 구현예에서, 핵산 분자는 다양한 유전자를 암호화할 수 있다. 전사될 때, 핵산 분자는 본원에 기술된 유전자에 대한 mRNA를 생산하고, 그런 다음 이는 원하는 또는 필요한 단백질로 번역된다.
본원에 기술된 바와 같이, 적절하게 포유동물 세포는 바이러스 헬퍼 유전자를 암호화하는 핵산 분자를 포함한다. 바이러스 헬퍼 유전자는 다양한 아데노바이러스 바이러스 유전자, 헤르페스 바이러스 유전자 및 보카바이러스 유전자를 포함한다 (예를 들어, Guido et al., "Human bocavirus: Current knowledge and future challenges," World J. Gateroenterol 22:8684-8697 참조, 이의 개시내용은 그 전문이 본원에 참고로 포함됨). 예시적인 구현예에서, 바이러스 헬퍼 유전자는 아데노바이러스 헬퍼 유전자이다. 본원에서 언급된 바와 같이, 용어 "아데노바이러스 헬퍼 유전자" 또는 "AV 헬퍼 유전자"는 아데노 관련 바이러스 복제 및 패키징에 기여하는 하나 이상의 아데노바이러스 하위유형 또는 혈청형으로부터 유래된 하나 이상의 핵산 서열로 구성되는 유전자를 지칭한다. 일부 구현예에서, 아데노바이러스 헬퍼 유전자는 E1A, E1B, E2A, E4 (E4Orf6 포함), VA, 또는 이의 조합 또는 임의의 다른 아데노바이러스 헬퍼 유전자이다. 예시적인 구현예에서, 아데노바이러스 헬퍼 유전자는 E2A와 E4Orf6 유전자 모두를 포함한다. 적절하게, 내부 리보솜 진입 부위 (IRES) 요소는 E2A와 E4Orf6 유전자 사이에 포함된다. IRES 요소는 단일 발현 카세트에서 E2A 유전자 다음에 E4Orf6 유전자의 번역을 개시하여, 작제물에 안정성을 제공한다.
본원에 기술된 다양한 유전자를 암호화하는 다양한 핵산 분자는 적절하게 탈억제 가능한 프로모터의 제어하에 있다. 본원에 사용된 "제어하에"는 "프로모터," "프로모터 서열," 또는 "프로모터 영역"에 의해 조절되는 유전자를 지칭하고, 이는 RNA 중합효소에 결합하고 다운스트림 코딩 또는 비코딩 유전자 서열의 전사를 개시할 수 있는 DNA 조절 영역/서열을 지칭한다. 다시 말해서, 프로모터 및 유전자는 작동 가능한 조합이거나 작동 가능하게 연결된다. 본원에서 언급된 바와 같이, 용어 "작동 가능한 조합으로", "작동 가능한 순서로" 및 "작동 가능하게 연결된"은 주어진 유전자의 전사 및/또는 원하는 단백질 분자의 합성을 지시할 수 있는 프로모터가 생산되는 방식으로 핵산 서열의 연결을 지칭한다. 용어는 또한 기능성 단백질이 생산되는 방식으로 아미노산 서열의 연결을 지칭한다.
본 개시내용의 일부 예에서, 프로모터 서열은 전사 개시 부위를 포함하고 업스트림으로 연장되어 배경 위에서 검출 가능한 수준에서 전사를 개시하는 데 필요한 최소 수의 염기 또는 요소를 포함한다. 일부 구현예에서, 프로모터 서열은 전사 개시 부위, 뿐만 아니라 RNA 중합효소의 결합을 담당하는 단백질 결합 도메인을 포함한다. 진핵생물 프로모터는 항상 그런 것은 아니지만, 종종 "TATA" 박스 및 "CAT" 박스를 함유할 것이다. 유도성 프로모터를 포함하는, 다양한 프로모터는 예를 들어, 본 개시내용의 숙주 세포 또는 벡터에서 유전자 발현을 유도하기 위해 사용될 수 있다. 일부 구현예에서, 프로모터는 누출 프로모터가 아니며, 즉, 프로모터는 본원에 기술된 바와 같은 임의의 유전자 산물을 구성적으로 발현하지 않는다. 다른 구현예에서 본원에 기술된 바와 같이, 프로모터는 구성적 프로모터이고, 이는 외부 조절의 영향과 무관하게 mRNA 합성을 개시한다.
적절하게, 본원에 기술된 AAV를 생산하기 위한 다양한 유전자의 전사를 제어하기 위해 사용되는 프로모터는 탈억제 가능한 프로모터다. 본원에 사용된 바와 같이, "탈억제 가능한 프로모터"는 기능적 프로모터 및 기능적 프로모터의 억제를 유발하기 위해 억제자 요소에 결합할 수 있는 추가 요소 또는 서열을 포함하는 구조를 지칭한다. "억제"는 프로모터에 의한 다운스트림 코딩 또는 비코딩 유전자 서열의 전사의 개시의 감소 또는 저해를 지칭한다. "억제자 요소"는 프로모터 (또는 프로모터 근처)에 결합 가능하여 프로모터의 활성을 감소시키거나 억제하는 단백질 또는 폴리펩티드를 지칭한다. 억제자 요소는 억제자 요소의 기질 또는 결합 파트너와 상호작용할 수 있고, 그리하여 억제자 요소는 입체형태 변화를 겪는다. 억제자 요소에서 이러한 입체형태 변화는 프로모터를 감소시키거나 저해하는 억제자 요소의 능력을 빼앗아, 프로모터의 "탈억제"를 초래하여, 프로모터가 전사의 개시를 진행할 수 있도록 한다. "기능적 프로모터"는 억제자 요소의 작용 부재로, 전사를 개시할 수 있는 프로모터를 지칭한다. 본 발명의 실시에 사용될 수 있는 다양한 기능적 프로모터는 당 업계에 공지되어 있고, 예를 들어, PCMV, PH1, P19, P5, P40 및 아데노바이러스 헬퍼 유전자의 프로모터 (예를 들어, E1A, E1B, E2A, E4Orf6, 및 VA)를 포함한다.
탈억제 가능한 프로모터로 사용될 수 있는 예시적인 억제자 요소 및 이들의 대응하는 결합 파트너는 당 업계에 공지되어 있고, 쿠메이트 유전자 스위치 시스템 (CuO 작동자, CymR 억제자 및 쿠메이트 결합 파트너) (예를 들어, Mullick et al., "The cumate gene-switch: a system for regulated expression in mammalian cells," BMC Biotechnology 6:43 (1-18) (2006) 참조, 본원에 기술된 탈억제 가능한 프로모터 시스템의 개시를 비롯한, 이의 개시내용은 그 전문이 본원에 참고로 포함됨) 및 본원에 기술된 TetO/TetR 시스템 (예를 들어, Yao et al., "Tetracycline Repressor, tetR, rather than the tetR-Mammalian Cell Transcription Factor Fusion Derivatives, Regulates Inducible Gene Expression in Mammalian Cells," Human Gene Therapy 9:1939-1950 (1998) 참조, 이의 개시내용은 그 전문이 본원에 참고로 포함됨)과 같은 시스템을 포함한다.
예시적인 구현예에서, 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다. 예시적인 탈억제 가능한 프로모터 시스템을 나타내는 개략도는 도 1에 제공된다. PCMV 프로모터를 포함하는 탈억제 가능한 프로모터, 및 PH1 프로모터를 포함하는 탈억제 가능한 프로모터를 나타내고, 모두 2개의 TetO 서열 (TetO2)을 포함한다. 개략적으로 예시된 바와 같이, TetO2 서열에 대한 2개의 테트라사이클린 억제자 단백질 (TetR - TetO2 서열에 대한 억제자 요소)의 결합 시, PCMV 프로모터와 PH1 프로모터 모두 억제된다. 즉, 이들 프로모터에서 전사가 거의 또는 전혀 발생하지 않는다. TetR에 대한 결합 파트너 (적절하게 독시사이클린 (Dox)의 결합 시, TetR 단백질은 입체형태를 변경하고, TetO2 서열로부터 방출하고, 기능적 프로모터는 자연스럽게, 이들의 정상 전사 과정을 시작한다. 도 1에 개략적으로 예시된 바와 같이, Dox가 첨가될 때 이는 "오프" 위치 (적절하게 PCMV 프로모터 및 PH1 프로모터로부터 전사가 발생하지 않는 장소)에서 "온" 위치로의 전체 시스템의 변화를 야기하고, PCMV 프로모터 및 PH1 프로모터가 이들의 제어하에 유전자를 전사하는 자연 상태로 돌아가도록 허용한다.
예를 들어, 도 1에 나타낸 바와 같이, TetO2 서열을 갖는 PCMV 프로모터 (적절하게 pcDNA4/TO 프로모터; INVITROGEN®)는 TetR에 의해 결합될 때, "오프" 위치에 있다. Dox가 첨가되면, TetR은 입체형태를 변경하고, 탈억제 가능한 프로모터의 TetO2 서열로부터 방출하고, PCMV 프로모터는 아데노바이러스 헬퍼 유전자 (예를 들어, E2A 및 E4) 전사를 진행한다.
본원에 기술된 바, 및 도 1에 예시된 바와 같이, 포유동물 세포는 제4 탈억제 가능한 프로모터의 제어하에 바이러스 관련 (VA), 비코딩 RNA를 암호화하는 핵산을 추가로 포함할 수 있다. 도 1에 나타낸 바와 같이, 이러한 탈억제 가능한 프로모터는 기능적 프로모터 PH1, 및 비코딩 RNA의 발현을 제어하는 TetO2 서열을 포함할 수 있다 (예를 들어, Wiederschain et al., "Single-vector inducible lentiviral RNAi system for oncology target validation, Cell Cycle 8:498-504 (2009) 참조, 프로모터 시스템 및 서열의 개시를 비롯한, 이의 개시내용은 그 전문이 본원에 참고로 포함됨). 도 1에 나타낸 바와 같이, TetO2 서열을 갖는 PH1 프로모터는 TetR에 의해 결합될 때, "오프" 위치이다. Dox가 첨가되면, TetR은 입체형태를 변경하고, 탈억제 가능한 프로모터의 TetO2 서열로부터 방출하고, PH1 프로모터는 VA 1 비코딩 RNA 전사를 진행한다.
도 2a는 다양한 포유동물 세포 및 본원에 기술된 방법에서 활용될 수 있는 예시적인 핵산 분자를 나타낸다. 예시된 바와 같이, CMV 프로모터는 IRES 요소를 통해 연결된, E2A 및 E4Orf6 유전자 모두의 업스트림에 사용된다. CMV 프로모터는 제어를 위해, 탈억제를 통해 CMV 인핸서 및 tet 작동자 (TetO2)를 포함한다. VA 비코딩 RNA의 발현을 제어하는, TetO2 서열을 또한 포함하는, H1 프로모터에 대한 예시적인 위치가 도 2a에 또한 예시된다.
도 1 및 도 2a는 또한 구현예에서, 포유동물 세포가 구성적 프로모터의 제어하에 억제자 요소를 포함할 수 있음을 예시한다. 본원에 기술된 바와 같이, 적절하게 암호화되는 억제자 요소는 테트라사이클린 억제자 단백질 (TetR)이다. 도 1 및 도 2a에 예시된 바와 같이, 억제자 요소의 발현에 대해 적합한 프로모터는 hPGK 프로모터이다. 억제자 요소를 구성적 프로모터의 제어하에 둠으로써, 억제자 요소, 적절하게 TetR의 생산은 항상 활성이다. 즉, TetR은 포유동물 세포로의 핵산 분자의 도입 시 생산된다. 이는 TetO2 서열에 결합하는 TetR에 의해 억제되는 다양한 탈억제 가능한 프로모터의 엄격한 제어를 제공한다.
도 2a에 나타낸 바와 같이, 예시적인 구현예에서, 테트라사이클린 억제자 단백질을 암호화하는 핵산과 함께 프레임 내에서 전사 억제 도메인을 암호화하는 핵산이 유도될 수 있다. 도 2a에서, 이 전사 억제 도메인은 TetR의 C-말단으로의 프레임에서 융합된, 크루펠-관련 박스 (KRAB) 서열이다 (예를 들어, Szulc et al., "A versatile tool for conditional gene expression and knockdown," Nature Methods 3:109-116 (2006) 참조). KRAB 서열, 또는 다른 전사 억제 도메인의 사용은 TetO2에 결합할 때 TetR의 억제 활성을 개선하여, 탈억제 전 (즉, Dox의 첨가 전) 누출 또는 기저 유전자 발현의 양을 최소화한다. 도 2b 및 도 12a는 KRAB 서열이 결여된 예시적인 핵산 분자를 나타낸다.
도 12a에 나타낸 바와 같이, 예시적인 구현예에서, 테트라사이클린 억제자 단백질을 암호화하는 핵산은 포유동물 세포 내에 포함되거나 안정적으로 발현될 수 있다. 도 2a 및 도 12b에서, 이 전사 억제 도메인은 TetR의 C-말단으로 프레임에서 융합된, 크루펠-관련 박스 (KRAB) 서열이다 (예를 들어, Szulc et al., "A versatile tool for conditional gene expression and knockdown," Nature Methods 3:109-116 (2006) 참조). KRAB 서열, 또는 다른 전사 억제 도메인의 사용은 TetO2에 결합할 때 TetR의 억제 활성을 개선하여, 탈억제 전 (즉, Dox의 첨가 전) 누출 또는 기저 유전자 발현의 양을 최소화한다. 도 2b 및 도 12a는 KRAB 서열이 결여된 예시적인 핵산 분자를 나타낸다.
구현예에서, 핵산 분자에 의해 암호화되는 AAV 유전자는 Rep 및 Cap 유전자를 포함한다. 핵산 분자에 의해 암호화될 수 있는 다른 AAV 유전자는 임의의 AAV 혈청형으로부터의 임의의 유전자를 포함한다. 일부 구현예에서, AAV 유전자는 Rep78, Rep68, Rep52, Rep40, VP1, VP2, VP3, 또는 이의 조합이다. 일부 구현예에서, AAV 유전자는 아데노 관련 바이러스 2형으로부터 유래된다. 일부 구현예에서, AAV 유전자는 아데노 관련 바이러스 Anc80으로부터 유래된다.
본원에서 언급된 바와 같이, 용어 "Rep" 유전자는 바이러스 게놈, 또는 AAV-2 DNA 복제를 매개하는 것으로 또한 알려진 인간 헤르페스바이러스 6 (HHV-6) rep 유전자와 같은 이의 기능적 동족체를 복제하기 위해 집합적으로 필요한 바이러스의 복제 단백질을 암호화하는 AAV 게놈의 기술 분야에서 인정되는 영역을 지칭한다. 따라서, rep 코딩 영역은 AAV Rep78 및 Rep68 ( "긴 형태의 Rep"), 및 Rep52 및 Rep40 ("짧은 형태의 Rep"), 또는 이의 기능적 동족체를 암호화하는 유전자를 포함할 수 있다. 본원에 사용된, rep 코딩 영역은 본원에 기술된 AAV 혈청형과 같은 임의의 바이러스 혈청형으로부터 유래할 수 있다. 영역은 모든 야생형 유전자를 포함할 필요는 없지만, rep 유전자가 적합한 표적 세포에서 발현될 때 충분한 통합 기능을 제공하는 한, 변경될 수 있다 (예를 들어, 뉴클레오티드의 삽입, 결실 또는 치환에 의함). 예를 들어 Muzyczka, N., Current Topics in Microbiol. and Immunol. 158:97-129 (1992); 및 Kotin, R. M., Human Gene Therapy 5:793-801 (1994) 참조.
본원에서 언급된 바와 같이, 용어 "Cap" 유전자는 바이러스의 캡시드 단백질을 암호화하는 the AAV 게놈의 기술 분야에서 인정되는 영역을 지칭한다. 이들 캡시드 단백질의 예시적인 (비제한적) 예는 AAV 캡시드 단백질 VP1, VP2, 및 VP3이다. 본 개시내용에서 사용되는 Cap 유전자는 임의의 AAV 혈청형 또는 AAV 혈청형의 조합으로부터 유래할 수 있다.
도 4a는 Rep 및 Cap 유전자의 자연적 위치 및 프로모터 드라이버를 나타낸다. 당 업계에 알려진 바와 같이, AAV의 성공적인 생산을 위해, Rep78과 Rep52 유전자의 비율은 최적 수준에서 유지되어야 한다. 예를 들어, Li et al., "Role for Highly Regulated rep Gene Expression in Adeno-Associated Virus Vector Production," Journal of Virology 71:5236-5243 (1997) (이의 개시내용은 그 전문이 본원에 참고로 포함됨)에서 논의된 바와 같이, Rep78 생산량의 제어는 DNA 복제를 방해할 수 있다. 게다가, Rep78 은 포유동물 세포에서 과도하게 생성되는 경우 독성이 있을 수 있다. 예를 들어, Clark et al., "Cell Lines for the Production of Recombinant Adeno-Associated Virus," Human Gene Therapy 6:1329-1341 (1995) 참조, 이의 개시내용은 그 전문이 본원에 참고로 포함되고, rep 단백질 수준을 높이는 것은 세포독성과 관련이 될 수 있음을 논의한다. 또한, Rep52 발현 (p19)을 위한 프로모터의 Rep78에 대한 코딩 영역 내에 위치한다. 본원에 기술된 바와 같이, 이러한 도전을 극복하기 위해 Rep 유전자 및 프로모터의 자연 위치에 다양한 변형이 이루어졌다.
예시적인 구현예에서, 포유동물 세포는 제2 탈억제 가능한 프로모터의 제어하에 Rep78 유전자 및 제3 탈억제 가능한 프로모터의 제어하에 Rep52 유전자를 암호화하는 핵산을 포함할 수 있다. 도 4b에 나타낸 바와 같이, 이 배열을 달성하는 한 가지 방법은 Rep78 유전자 내에서 Rep52 유전자를 제거하고, 이를 Rep78 및 Cap 유전자의 다운스트림에 배치하는 것이다. Rep78 유전자는 탈억제 가능한 프로모터 (p5)의 제어하에 있을 수 있고, 그것은 TetO2 서열을 포함한다. 이러한 구현예에서, Rep78 내의 천연 p19 프로모터는 침묵되도록 변형되거나 돌연변이된다. 제거된 Rep52 유전자는 또한 TetO2 서열을 포함하는 탈억제 가능한 프로모터 (p19)의 제어하에 배치된다.
도 5는 Rep78의 p5 프로모터에 대한 변형을 위한, TATA 박스, rep-결합 요소 (RBE) 및 개시자 요소 (INR)에 관하여 각각의 TetO 서열의 3개의 잠재적 위치를 나타낸다. 야생형 p5 프로모터가 또한 개략적으로 도시된다. 도 6은 Rep52에 대한 p19 프로모터의, TATA 박스 및 Sp1 전사 인자에 관하여 각각의 TetO 서열의 3개의 잠재적 위치를 나타낸다. 야생형 p19 프로모터가 또한 개략적으로 도시된다. TetO 서열의 추가 위치가 또한 본원에 포함되고 당업자에 의해 용이하게 구상될 수 있다.
또 다른 추가 구현예에서, Rep78 유전자는 탈억제 가능한 프로모터의 제어하에 있을 수 있고, 그리고 Rep52 유전자는 인공 인트론 내에 함유된 탈억제 가능한 프로모터의 제어하에 있을 수 있다. 이러한 구현예는 도 4c에 개략적으로 표현된다. 예시된 바와 같이, 탈억제 가능한 p5 프로모터 (예를 들어, 본원에 기술된 바와 같은 TetO2 서열을 포함)는 Rep78 유전자의 업스트림에 배치된다. 인트론 (In-i-p19로 지정됨) 내에 함유된 탈억제 가능한 p19 프로모터 (예를 들어, TetO2 서열을 포함)는 Rep52의 발현을 제어한다. 이러한 구현예의 개략도는 도 7a에 제공되고, 여기서 2개의 tet 작동자 서열은 키메라 인트론 내에 도시되어 있다. 이 키메라 인트론은 p19 프로모터의 구성요소에 관하여 다양한 위치에서 삽입될 수 있다. 예를 들어, 도 7b에 나타낸 바와 같이, 인트론 서열은 p19 프로모터의 TATA-2의 다운스트림에 적절하게 배치된다. 간격은 예를 들어, TATA-2 서열로부터 약 1 내지 25개 염기 쌍 다운스트림일 수 있다.
본원에 기술된 바와 같이, 예시적인 구현예에서, 핵산 분자에 의해 암호화된 Cap 유전자는 적절하게 고유 프로모터의 제어하에 있다. 즉, 원하는 경우 탈억제 가능한 프로모터를 사용할 수 있지만, Cap 유전자는 탈억제 가능한 프로모터의 제어하에 있을 필요가 없다. 적합한 구현예에서, Cap 유전자는 p40 프로모터의 제어하에 있다.
예시적인 구현예에서, 핵산 분자는 2개의 역위 말단 반복 (ITR) 서열을 포함한다. 당 업계에 공지된 바와 같이, 이들 ITR 서열 (즉, AAV2 ITR)은 뉴클레오티드의 단일 가닥 서열이고, 이의 역 상보가 다운스트림에 이어진다. ITR 서열은 AAV 게놈의 복제, 구조, 패키징 및 통합에 필요한 최소 서열을 나타낸다. 적절하게, 이들 ITR 서열은 관심 유전자 측면에 있다. 따라서, 구현예에서, 핵산 분자는 관심 유전자를 추가로 암호화한다. 이 관심 유전자는 예를 들어, 리포터 유전자, 선별 유전자, 또는 치료적 관심 유전자일 수 있다.
예를 들어, 도 10c에 도시된 바와 같이, 관심 유전자, 예를 들어 녹색 형광 단백질 (EGFP)을 암호화하는 유전자는 2개의 ITR 서열이 측면에 있다.
"유전자"는 폴리펩티드를 암호화하고, cDNA 및 게놈 DNA 핵산 분자를 포함하는 뉴클레오티드의 조립체를 지칭한다. "유전자"는 코딩 서열에 선행 (5' 비코딩 서열)하고 후행 (3' 비코딩 서열)하는 조절 서열로서 작용하는 핵산 단편을 또한 지칭한다. 일부 구현예에서, 유전자는 다중 카피와 통합된다. 일부 구현예에서, 유전자는 미리 정의된 카피 수로 통합된다.
본원에서 언급된 바와 같이, 용어 "관심 유전자" 또는 "GOI"는 이종 유전자를 기술하기 위해 사용된다. 본원에서 언급된 바와 같이, 코딩 서열 또는 제어 서열과 같은 핵산 서열에 관련하여 용어 "이종 유전자" 또는 "HG"는 특정 세포와 일반적으로 함께 연결되지 않고/거나 일반적으로 연관되지 않는 핵산 서열, 예를 들어 유전자를 표시한다. 일부 구현예에서, 이종 유전자는 코딩 서열 자체가 자연에서 발견되지 않는 작제물이다 (예를 들어, 천연 유전자와 상이한 코돈을 갖는 합성 서열). 대립 유전자 변이 또는 자연 발생 돌연변이 사건은 본원에서 사용되는 이종 DNA를 생성하지 않는다.
본원에서 언급된 바와 같이, "리포터 유전자"는 그 발현이 용이하게 확인되고 측정될 수 있는 세포에 표현형을 부여하는 유전자이다. 일부 구현예에서, 리포터 유전자는 형광 단백질 유전자를 포함한다. 일부 구현예에서, 리포터 유전자는 선별 유전자를 포함한다.
본원에서 언급된 바와 같이, 용어 "선별 유전자"는 필수 영양소 외에는 결여된 배지에서 성장하는 능력을 부여하는 효소 활성을 인코딩하는 유전자의 사용을 지칭하고; 게다가, 선별 유전자는 선별 유전자가 발현되는 세포에 항생제 또는 약물에 대한 내성을 부여할 수 있다. 선별 유전자는 숙주 세포에 특정 표현형을 부여하기 위해 사용될 수 있다. 숙주 세포가 선별 배지에서 성장하기 위해 선별 유전자를 반드시 발현해야 하는 경우, 유전자를 양성 선별 유전자라고 한다. 선별 유전자는 또한, 특정 유전자를 함유하는 숙주 세포를 피해 선별하기 위해 사용될 수 있고; 이 방식으로 사용되는 선별 유전자는 음성 선별 유전자로서 지칭된다.
본원에서 언급된 바와 같이, 용어 "치료적 관심 유전자"는 임의의 기능적으로 관련된 뉴클레오티드 서열을 지칭한다. 따라서, 본 개시내용의 치료적 관심 유전자는 표적 세포 결함이 있거나 누락된 단백질을 암호화하거나 원하는 생물학적 또는 치료적 효과 (예를 들어, 항바이러스 기능)를 갖는 비-천연 단백질을 암호화하는 임의의 원하는 유전자를 포함할 수 있거나, 서열은 안티센스 또는 리보자임 기능을 갖는 분자에 대응할 수 있다. 적합한 치료적 관심 유전자의 대표적인 (비제한적) 예시는 AIDS, 암, 신경 질환, 심혈관 질환, 고콜레스테롤혈증과 같은 장애를 비롯한, 염증성 질환, 자가 면역, 만성 및 감염성 질환; 다양한 빈혈, 지중해 빈혈 및 혈우병을 포함한 다양한 혈액 질환; 낭포성 섬유증, 고셔병, 아데노신 데아미나제 (ADA) 결손증, 폐기종 등과 같은 유전적 결함의 치료에 사용되는 것을 포함한다. 암 및 바이러스 질환에 대한 안티센스 요법에서 유용한 여러 안티센스 올리고뉴클레오티드 (예를 들어, mRNA의 전사 개시 부위 (AUG 코돈) 주변 서열에 상보적인 짧은 올리고뉴클레오티드)가 당 업계에 기술되어 있고 또한 적합한 치료적 관심 유전자의 예이다.
일부 구현예에서, 본원에 제공된 포유동물 세포는 헬퍼 바이러스가 실질적으로 없다. 본원에서 언급된 바와 같이, "헬퍼 바이러스"는 아데노 관련 바이러스의 복제 및 패키징을 가능하게 하기 위해 추가되는 임의의 비-AAV 바이러스이다. 헬퍼 바이러스의 대표적인 (비제한적) 예는 아데노바이러스 및 헤르페스 바이러스이다. 일부 구현예에서, 헬퍼 바이러스가 실질적으로 없는 용어는 세포당 100개 미만, 10개 미만, 또는 1개 미만 헬퍼 바이러스를 갖는 세포를 지칭한다. 일부 구현예에서, 헬퍼 바이러스가 실질적으로 없는 용어는 헬퍼 바이러스가 존재하지 않는 세포 또는 당업자에게 공지된 검출 방법을 사용하여 헬퍼 바이러스가 존재하지 않는 세포 집단을 지칭한다. 일부 구현예에서, 야생형 헬퍼 바이러스가 세포에 없다. 일부 구현예에서, 용어 야생형 바이러스는 임의의 다른 바이러스와 독립적으로 세포에서 복제할 수 있는 임의의 완전 비-AAV 바이러스를 지칭한다.
본원에 기술된 AAV 생산자 세포는 대규모 AAV 제조를 위한 장기 및 비용-효율적인 해결책을 제공한다. 헬퍼 또는 Rep 단백질의 구성적 발현이 세포독성일 수 있으므로, 본원에 기술된 전략은 조작된, 탈억제 가능한 프로모터에 의해 이들의 발현의 제어를 허용한다.
또 다른 추가 구현예에서, 단일 핵산 분자에서, 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 바이러스 관련, 제3 탈억제 가능한 프로모터의 제어하에 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 서열을 포함하는, 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포가 본원에서 제공된다. 이러한 구현예에서, 이 단일 핵산 분자는 세포 내에 AAV의 생산을 가능하게 하기 위해 다른 필요한 요소와 함께, 다양한 서열 모두를 포함한다.
도 10a 및 10b는 AAV를 생산하기 위해 포유동물 세포에서 활용될 수 있는 이들 다양한 서열을 포함하는 예시적인 핵산 분자를 나타낸다.
본원에 기술된 바와 같이, 적절하게 포유동물 세포는 포유동물 세포 배양물이고, 구현예에서, 현탁 배양물일 수 있다. 본원에 기술된 바와 같이, 현탁 세포 배양물의 사용은 AAV의 증가된 확장성 및 생산을 허용한다.
본원에 기술되고 도 1, 2a-2b, 및 10a-10b에 나타낸 바와 같이, 적절하게 단일 핵산 분자는 E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 포함한다.
Rep78 및 Rep52 유전자를 포함하는, Rep 및 Cap 유전자를 암호화하기 위한 다양한 작제물이 본원에서 기술된다. 구현예에서, Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있다 (예를 들어, 도 4b에 나타낸 바와 같이, Rep52 유전자는 Rep78 유전자와 분리됨). 추가 구현예에서, 예를 들어 도 4c 및 7a-7b를 참조하여 본원에서 기술된 바와 같이, Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 배치될 수 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 배치될 수 있다. 적절하게, Cap 유전자는 고유 프로모터의 제어하에 있다.
다양한 탈억제 가능한 프로모터가 본원에서 기술되고, 구현예에서, 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다. 구현예에서, 제1 탈억제 가능한 프로모터의 기능적 프로모터 (즉, E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자의 발현을 제어함)는 거대세포바이러스 (CMV) 프로모터이다.
구현예에서 본원에 기술되고, 도 1, 2a-2b, 및 10a-10d에서 도시된 바와 같이, 적절하게 탈억제 가능한 프로모터의 억제자 요소는 구성적 프로모터의 제어하에 있어, 항상 탈억제 가능한 프로모터의 제어하에 다른 유전자의 발현을 제한하기 위해 생산된다. 적절하게, 암호화되는 억제자 요소는 탈억제 가능한 프로모터로서 작용하기 위해 TetO2 서열에 대한 결합을 위한 테트라사이클린 억제자 단백질이다. 구현예에서, 예를 들어 도 2a, 10a 및 10c에 나타낸 바와 같이, 전사 억제 도메인 (예를 들어, KRAB 서열)을 암호화하는 핵산은 테트라사이클린 억제자 단백질을 암호화하는 핵산과 함께 프레임에 포함된다. 이 전사 억제 도메인은 TetO2에 결합할 때, TetR의 개선된 억제 활성을 제공하여, 탈억제 전 누출 또는 기저 유전자 발현의 양을 최소화한다.
본원에서 기술된 구현예 및 방법에서 사용될 수 있는 예시적인 포유동물 세포는 전체에 기술되어 있고, 예를 들어, 차이니즈 햄스터 난소 (CHO) 세포, 뿐만 아니라 인간 배아 신장 (HEK, 예를 들어 HEK293) 세포를 포함하는 인간 세포를 포함한다.
본원에 기술된 바와 같이, 적절하게 포유동물 세포는 분자 관심 유전자 (GOI)를 암호화하는 핵산을 추가로 포함한다. 도 10c-10d에 나타낸 바와 같이, 적절하게 GOI는 2개의 ITR 서열 사이에 포함된다.
또한, 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 바이러스 관련, 제3 탈억제 가능한 프로모터의 제어하에 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 단리된 핵산 분자가 본원에서 제공된다.
본원에 사용된 "단리된 핵산 분자"는 단리된 핵산 분자, 뿐만 아니라 단리된 핵산 분자가 다양한 세포 형질감염 시스템에서 조작, 저장, 수송, 및 활용될 수 있는 유사한 구조를 함유할 수 있는 벡터 및 플라스미드를 포함한다. 본원에 기술된 단리된 핵산 분자는 본원에 기술된 바와 같이 AAV의 생산을 위해 사용될 수 있지만, 또한, 다양한 비-AAV 생산 세포주 (일시적 형질감염 시스템을 포함)에서 활용될 수 있다. 본원에 기술된 단리된 핵산 분자는 적절하게 본원에 기술된, 포유동물 세포를 포함하는 세포 시스템에서 사용을 허용하기 위해 필요한 다양한 추가 요소 및 서열을 추가로 포함한다.
예를 들어, 도 10a-10b에 나타낸 바와 같이, 2개의 작제물을 나타낸다. 지시된 바와 같이, 구현예에서, 내부 리보솜 진입 부위 (IRES) 요소는 E2A와 E4Orf6 유전자 사이에 포함될 수 있다. 구현예에서 도 4b를 참조하여 본원에 기술된 바와 같이, Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있다 (즉, Rep52 유전자와 분리됨).
추가 구현예에서, 도 10a-10b를 참조하여 나타낸 바와 같이, Rep78 유전자는 탈억제 가능한 프로모터 (도 5에 나타낸 ip5 프로모터, 및 기술된 다양한 반복)의 제어하에 있고 Rep52 유전자는 ip19로서 도시되고, 도 7a-7b를 참조하여 기술된, 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있다. 단리된 핵산은 추가로 적절하게 고유 프로모터 (즉, p40)의 제어하에 Cap 유전자를 포함한다.
본원에 기술된 바와 같이, 다양한 탈억제 가능한 프로모터는 단리된 핵산 분자에 포함될 수 있고, 적절하게 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다. 도 10a 및 10b에 나타낸 바와 같이, 헬퍼 유전자 E2 및 E4에 관련하여, 적절하게 이 기능적 프로모터는 CMV 프로모터이고, 이는 TetO2 서열을 포함한다. 바이러스 관련, 비코딩 RNA와 함께 사용하기 위한 탈억제 가능한 프로모터는 적절하게 H1 프로모터, 뿐만 아니라 TetO2 서열을 포함한다.
본원에 기술되고 도 10a 및 10b에 나타낸 바와 같이, 억제자 요소 (예를 들어, 테트라사이클린 억제자 단백질)는 적절하게 구성적 프로모터, 예를 들어, hPGK 프로모터의 제어하에 있다. 도 10a 및 12b에 나타낸 바와 같이, 단리된 핵산 분자는 전사 억제 도메인 (예를 들어, KRAB 서열)을 암호화하는 핵산을 테트라사이클린 억제자 단백질을 암호화하는 핵산과 함께 프레임 안에 추가로 포함할 수 있다. 도 10c-10d 및 도 11b에 나타낸 바와 같이, 단리된 핵산 분자는 적절하게 2개의 ITR 서열 사이에 관심 유전자 (GOI, 예를 들어, GFP)를 추가로 포함할 수 있다.
본원에 기술되고 도 12a-12b에 나타낸 바와 같이, 억제자 요소는 적절하게 절연인자, 예를 들어, 닭 과민성 부위-4 (cHS4) 서열이 측면에 있다.
구현예에서, 전사 억제 도메인 (예를 들어 KRAB)을 암호화하는 핵산은 테트라사이클린 억제자 단백질 (예를 들어, TetR-KRAB)을 암호화하는 핵산과 함께 프레임 안에 포함된다.
본원에 기술된 단리된 핵산 분자에 포함하기 위한 추가 유전적 및 서열 요소는 당 업계에 공지되어 있고 도 10a-10d 및 도 11a-11e에 개략적으로 도시된 것을 찾을 수 있다.
본원에 기술된 핵산 서열의 맥락에서 용어 "서열 동일성" 또는 "% 동일성"은 특정 비교 창 위에 정렬될 때 동일한 비교 서열에서 잔기의 백분율을 지칭한다. 비교 창은 서열이 정렬되고 비교될 수 있는 적어도 10 내지 1000개 초과 잔기의 세그먼트일 수 있다. 서열 동일성의 측정을 위한 정렬 방법은 널리 공지되어 있고 BLAST (blast.ncbi.nlm.nih.gov/Blast. CGI.)와 같은 공개 데이터베이스를 사용하여 수행할 수 있다.
일부 구현예에서, 핵산 분자는 참조 핵산 분자 (또는 참조 폴리펩티드 또는 핵산 분자의 단편)와 각각, 적어도 약 70%, 적어도 약 75%, 적어도 약 80%, 적어도 약 85%, 적어도 약 90%, 적어도 약 95%, 적어도 약 97%, 적어도 약 98%, 적어도 약 99% 또는 약 100% 서열 동일성을 갖는다. 본 개시내용의 특정 구현예에서, 폴리펩티드 또는 핵산 분자는 참조 핵산 분자 (참조 핵산 분자의 단편)와 각각, 적어도 70%, 적어도 75%, 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 적어도 97%, 적어도 98%, 또는 적어도 99% 또는 100% 서열 동일성을 갖는다. 일부 구현예에서, 핵산 분자는 참조 핵산 분자와 각각, 약 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% 서열 동일성을 갖는다.
"벡터" 또는 "발현 벡터"는 본원에 기술된 핵산 분자가 세포에 부착된 핵산 분자의 복제 및/또는 발현을 가져오기 위해 부착될 수 있는 플라스미드, 파지, 바이러스, 또는 코스미드와 같은 레플리콘이다. "벡터"는 에피솜 (예를 들어, 플라스미드) 및 비-에피솜 벡터를 포함한다. 용어 "벡터"는 시험관 내, 생체 내, 또는 생체 외로 세포 내로 핵산 분자를 도입하기 위한 바이러스 및 비바이러스 수단 모두를 포함한다. 용어 벡터는 합성 벡터를 포함할 수 있다. 벡터는 형질 감염, 형질 도입, 세포 융합 및 리포펙션을 포함하지만 이에 제한되지 않는 잘 알려진 방법에 의해 원하는 숙주 세포로 도입될 수 있다. 벡터는 프로모터를 포함하는 다양한 조절 요소를 포함할 수 있다.
또한, 포유동물 세포에서 아데노 관련 바이러스 (AAV)를 생산하는 방법이 본원에서 제공된다. 적절하게, 본원에 기술된 방법은 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 단리된 핵산 분자로 형질 감염시키는 것을 포함한다.
본원에 사용된 "형질감염"은 세포 내로 벡터를 포함하는, 외인성 핵산 분자의 도입을 의미한다. "형질감염된" 세포는 세포 내부에 외인성 핵산 분자를 포함하고 "형질전환된" 세포는 세포 내의 외인성 핵산 분자가 세포에서 표현형 변화를 유도하는 세포이다. 형질감염된 핵산 분자는 숙주 세포의 게놈 DNA로 통합될 수 있고/거나 세포에 의해 일시적으로 또는 연장된　기간 동안　염색체 외로　유지될 수 있다. 외인성 핵산 분자 또는 단편을 발현하는 숙주 세포 또는 유기체는 "재조합," "형질전환된," 또는 "유전자이식" 유기체로 지칭된다. 다수의 형질감염 기술이 일반적으로 당 업계에 알려져 있다. 예를 들어, Graham et al., Virology, 52:456 (1973); Sambrook et al., Molecular Cloning, a laboratory manual, Cold Spring Harbor Laboratories, New York (1989); Davis et al., Basic Methods in Molecular Biology, Elsevier (1986); 및 Chu et al., Gene 13:197 (1981) 참조. 이러한 기술은 적합한 숙주 세포 내로 하나 이상의 외인성 DNA 모이어티, 예를 들어 AAV 벡터 카세트, AAV 헬퍼 작제물, 및 다른 핵산 분자를 도입하는데 사용될 수 있다.
본원에 기술된 단리된 핵산 분자 (즉, 벡터)를 사용하여 포유동물 세포를 형질 감염시키는 다양한 방법은 당 업계에 공지되고 다양한 화학적 및 물리적 방법, 예를 들어, 전기천공, 세포 주입, 인산 칼슘 노출, 리포좀 또는 중합체 기반 담체 시스템 등을 포함한다.
예시적인 구현예에서, PIGGYBAC™ 트랜스포존과 같은 벡터가 이들 핵산 분자의 안정한 통합을 위해　사용될 수 있고, 이는 세포 게놈에서 임의로 다중 카피에서 큰 핵산 서열의 원-스텝 삽입을 허용한다. 시스템은 PIGGYBAC™ 벡터 및 트랜스포존-특이적 역위 말단 반복 (ITR)를 인식하는 수퍼 PIGGYBAC™ 전위효소로 이루어지고 TTAA 부위에서 ITR과 개재 DNA를 게놈으로 효율적으로 통합한다. 수퍼 PIGGYBAC™ 전위효소는 수퍼 PIGGYBAC™ 전위효소 발현 벡터를 통해 세포로 전달되고, 이는 하나 이상의 PIGGYBAC™ 벡터로 공동형질감염된다.
방법은 포유동물 세포를 억제자 요소의 결합 파트너로 처리하는 것을 추가로 포함한다. 본원에 기술된 바와 같이, 억제자 요소의 존재하에, 핵산 분자에 의해 암호화되는 다양한 유전자의 전사를 제어하는 탈억제 가능한 프로모터의 기능적 프로모터가 억제된다. 즉, 유전자는 활동적으로 전사되지 않고, 대신 탈억제를 기다린다. 본원에 언급된 바와 같이, 탈억제 가능한 프로모터의 억제자 요소는 적절하게 구성적 프로모터의 제어하에 있어, 억제자 요소는 포유동물 세포 내로 핵산 분자의 형질감염된 직후 생성된다. 억제자 요소의 결합 파트너로 처리할 때, 억제자 요소는 결합 파트너에 결합하고, 입체형태를 변경하고, 더는 탈억제 가능한 프로모터를 억제하지 않는다. 이는 포유동물 세포 내의 제1, 제2 및 제3 (및 필요에 따라 추가의) 탈억제 가능한 프로모터 (즉, 탈억제 가능한 프로모터의 기능적 프로모터)의 활성화를 초래한다.
활성화 후, 다양한 요소가 포유동물 세포 내로 전사되고 번역되어, AAV의 생산을 초래한다. 그런 다음 AAV는 당 업계에 알려진 방법을 사용하여 수확된다.
본원에 기술된 방법은 포유동물 세포 배양물을 포함하는, 임의의 포유동물 세포에서 활용할 수 있지만, 적절하게 포유동물 세포 배양물은 HEK 현탁　세포 배양물과 같은 인간 세포를 포함하는, 현탁 배양물이다.
전체에 걸쳐 기술된 바와 같이 핵산 분자는 E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함할 수 있다. 제2 탈억제 가능한 프로모터의 제어하에 Rep78 유전자 및 제4 탈억제 가능한 프로모터의 제어하에 Rep52 유전자를 포함하는, Rep78 및 Rep 52 유전자에 관련된 예시적인 작제물이 본원에서 기술된다. 방법의 추가 구현예에서, Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있다.
본원에 기술된 바와 같이, 인공 인트론의 사용은 탈억제 가능한 프로모터를 활성화한 후 AAV를 생산하기 전에 제4 탈억제 가능한 프로모터의 제거를 허용한다. 본원에 기술된 바와 같이, 인트론 내의 탈억제 가능한 프로모터는 활성화 전 Rep52 유전자 발현의 억제를 보장하고, 반면 mRNA 스플라이싱 동안 인트론의 제거 후 Rep78 단백질의 발현을 여전히 허용한다. 방법의 예시적인 구현예에서, Cap 유전자는 고유 프로모터, 예를 들어 p40의 제어하에 있다.
구현예에서, 헬퍼 유전자의 발현을 제어하는 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다. 적절하게, 본원에 기술된 방법에서 암호화된 억제자 요소는 테트라사이클린 억제자 단백질이고, 적절하게 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다. 구현예에서, 억제자 요소는 예를 들어 암호화된 억제자 요소가 테트라사이클린 억제자 단백질일 때, 구성적 프로모터, 예를 들어 hPGK의 제어하에 있다.
본원에 기술된 바와 같이, TetR 및/또는 TetR-KRAB 억제자 요소를 활용하는 구현예에서, 세포를 독시사이클린으로 처리하는 것은 TetR의 입체형태를 변경하고 다양한 유전자의 전사를 활성화한다.
인간 세포 예를 들어 인간 배아 신장 (HEK) 세포, 또는 차이니즈 햄스터 난소 (CHO) 세포를 포함하는 다른 포유동물 세포를 포함하는 다양한 포유동물 세포가 본원에 기술된 방법에서 활용될 수 있다.
전체에 걸쳐 기술된 바와 같이, 구현예에서, AAV는 관심 유전자를 암호화하는 핵산 분자를 포함한다. 이 GOI는 리포터 유전자, 선별 유전자, 또는 치료적 관심 유전자를 포함하는, 임의의 다른 관심 유전자일 수 있다.
AAV를 생산하는 방법은 연속 제조 시스템에서 사용될 수 있다. 예시적인 구현예에서, 현탁 세포 배양의 사용은 각각의 시작 세포 배치에 대해 AAV의 다중 수확을 허용하는 높은 생산성 및 연장된 배양 조건을 갖는 대량의 AAV의 생산을 허용한다.
생산 방법은 교반 탱크, 공중수송, 섬유, 초극세사, 유공 섬유, 세라믹 매트릭스, 유동층, 고정층, 및/또는 분류층 생물반응기를 포함하지만, 이에 제한되지 않는 임의의 적합한 반응기(들)를 활용할 수 있다. 본원에 사용된 바와 같이, "반응기"는 발효기 또는 발효 유닛, 또는 임의의 다른 반응 용기를 포함할 수 있고 용어 "반응기"는 "발효기"와 상호 교환적으로 사용된다. 용어 발효기 또는 발효는 미생물 및 포유류 배양을 모두 지칭한다. 예를 들어, 일부 양태에서, 예시 생물반응기 유닛은 다음 중 하나 이상, 또는 모두를 수행할 수 있다: 영양분 및/또는 탄소 공급원 공급, 적합한 가스 (예를 들어, 산소)의 주입, 발효 또는 세포 배양 배지의 입구 및 출구 흐름, 기체 및 액체 상 분리, 온도 유지, 산소 및 CO2 수준 유지, pH 수준 유지, 휘저어 섞음 (예를 들어, 교반), 및/또는 세척/살균. 예시 반응기 유닛, 예를 들어 발효 유닛은 유닛 내에 다중 반응기를 함유할 수 있고, 예를 들어 유닛은 각각의 유닛에서 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 또는 100개, 또는 이상의 생물반응기를 가질 수 있고/거나 설비는 설비 내에 단일 또는 다중 반응기를 갖는 다중 유닛을 포함할 수 있다. 다양한 구현예에서, 생물반응기는 배치, 반유가식, 유가식, 및/또는 연속 발효 공정에 적합할 수 있다. 임의의 적합한 반응기 직경이 사용될 수 있다. 구현예에서, 생물반응기는 약 100 mL 및 약 50,000 L 사이의 용적을 가질 수 있다. 비제한적 예시는 100 mL, 250 mL, 500 mL, 750 mL, 1 리터, 2 리터, 3 리터, 4 리터, 5 리터, 6 리터, 7 리터, 8 리터, 9 리터, 10 리터, 15 리터, 20 리터, 25 리터, 30 리터, 40 리터, 50 리터, 60 리터, 70 리터, 80 리터, 90 리터, 100 리터, 150 리터, 200 리터, 250 리터, 300 리터, 350 리터, 400 리터, 450 리터, 500 리터, 550 리터, 600 리터, 650 리터, 700 리터, 750 리터, 800 리터, 850 리터, 900 리터, 950 리터, 1000 리터, 1500 리터, 2000 리터, 2500 리터, 3000 리터, 3500 리터, 4000 리터, 4500 리터, 5000 리터, 6000 리터, 7000 리터, 8000 리터, 9000 리터, 10,000 리터, 15,000 리터, 20,000 리터, 및/또는 50,000 리터의 용적을 포함한다. 추가로, 적합한 반응기는 다회용, 단회용, 일회용, 또는 비-일회용일 수 있고 스테인리스 스틸 (예를 들어, 316L 또는 임의의 다른 적합한 스테인리스 스틸)과 같은 금속 합금 및 인코넬, 플라스틱, 및/또는 유리를 포함하는 임의의 적합한 재료로 형성될 수 있다.
구현예에서 및 본원에서 명시하지 않는 한, 본원에 기술된 장치, 설비, 및 방법은 또한 달리 언급되지 않은 임의의 적합한 유닛 작동 및/또는 장비, 예를 들어 이러한 생성물의 분리, 정제, 및 단리를 위한 작동 및/또는 장비를 포함할 수 있다. 임의의 적합한 설비 및 환경 예를 들어 전통적인 스틱형 설비, 모듈식, 이동식 및 임시 설비, 또는 임의의 다른 적합한 건축물, 설비, 및/또는 레이아웃이 또한 사용된다. 예를 들어, 일부 구현예에서 모듈식 청정실이 사용될 수 있다. 추가적으로 그리고 달리 명시되지 않는 한, 본원에 기술된 장치, 시스템, 및 방법은 단일 위치 또는 설비에서 수용 및/또는 수행될 수 있거나 대안적으로 개별 또는 여러 위치 및/또는 설비에서 수용 및/또는 수행될 수 있다.
추가 구현예에서, 본원에서 하기 단계를 포함하는 아데노 관련 바이러스 (AAV)를 사용하는 치료 방법이 제공된다: 하기를 암호화하는 단리된 핵산 분자로 포유동물 세포를 형질 감염시키는 단계: 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 바이러스 관련, 제3 탈억제 가능한 프로모터의 제어하에 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소, 포유동물 세포를 억제자 요소의 결합 파트너로 처리하는 단계, 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화하는 단계, AAV를 생산하는 단계, AAV를 수확하는 단계, 및 AAV를 포유동물 환자에 투여하는 단계.
적절하게, 방법은 치료적 관심 유전자를 포함하는, 관심 유전자를 갖는 인간 환자를 치료하기 위해 사용된다. 인간 환자에 대한 투여는 예를 들어, 흡입, 주사 또는 정맥 내 투여, 뿐만 아니라 당 업계에 공지된 다른 투여 방법을 포함할 수 있다.
AAV를 생산하는 방법 및 다양한 탈억제 가능한 프로모터의 용도가 본원에서 기술된다.
추가 구현예에서, 아데노 관련 바이러스 (AAV)를 생산하는 방법이 제공되고 하기로 TetR 및/또는 TetR-KRAB을 암호화하는 하나 이상의 핵산을 안정적으로 발현하는 포유동물 세포를 형질 감염시키는 단계: 제1 탈억제 가능한 프로모터의 제어하에, E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자를 암호화하는 제2 핵산, 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산; 포유동물 세포를 TetR의 결합 파트너로 처리하는 단계; 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화하는 단계; AAV를 생산하는 단계; 및 AAV를 수확하는 단계를 포함한다.
본원에 기술된 바와 같이, 적절하게 포유동물 세포는 현탁 배양물을 포함하는 포유동물 세포 배양물이다.
본원에 기술된 바와 같이, 적절하게 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포 또는 인간 배아 신장 (HEK) 세포를 포함하는 인간 세포이다.
본원에 기술된 바와 같이, 포유동물 세포를 형질 감염시키기 위해 2 또는 3개의 상이한 핵산 또는 트랜스포존을 사용하는 것은 하나의 플라스미드에서 핵산을 조합하는 것보다, 개별 AAV-생산 및 패키징 구성요소의 비율을 최적화하여 각각의 트랜스포존의 발현에 시간적 통제를 행사하는 능력을 포함하는 장점을 제공한다.
본원에 기술된 바와 같이, 적절하게 E2A 및 E4Orf6 유전자를 암호화하는 핵산은 E2A 와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함한다.
본원에 기술된 바와 같이, 적절하게 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다.
본원에 기술된 바와 같이, 적절하게 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다.
일부 구현예에서, 아데노 관련 바이러스 (AAV)를 생산하기 위해 사용되는 포유동물 세포는 구성적 프로모터의 제어하에 TetR 및/또는 TetR-KRAB을 암호화하는 하나 이상의 핵산을 안정적으로 발현한다.
본원에 기술된 바와 같이, (적절하게 트랜스포존을 통해, 바이러스의 구성요소를 운반하는 핵산의 삽입 전) 포유동물 세포에서 TetR 및/또는 TetR-KRAB의 안정한 발현은 형질감염에 의해 도입되는 잠재적 세포독성 AAV 유전자의 억제를 최대화하고 탈억제 가능한 프로모터 요소에 대한 증가된 시간적 제어를 부여한다.
일부 구현예에서, KRAB 억제자 도메인은 TetR과 프레임에 융합된다.
본원에 기술된 바와 같이, KRAB 억제자 도메인을 TetR과 프레임에 융합하는 것은 잠재적 세포독성 AAV-패키징 핵산의 "누출" 발현이 덜 발생하는 것을 보장한다. TetR 억제자 도메인과 프레임 안에 융합된 KRAB 억제자 도메인은 탈억제 가능한 프로모터의 높은 수준의 억제를 달성하기 위한 추가 메커니즘을 제공한다.
일부 구현예에서, 포유동물 세포는 충분한 양의 TetR을 생산한다. 본원에 사용된 바와 같이, "충분한" TetR은 억제 가능한 및 탈억제 가능한 요소의 발현 및/또는 활성을 중지하기 위한 (즉, 독시사이클린의 첨가 전) 억제자 (예를 들어, TetR)의 양 및/또는 활성의 수준으로 정의된다.
본원에 기술된 바와 같이, 충분한 양의 TetR을 생산하는 것이 정상 조건하에 탈억제 가능한 프로모터의 억제를 위해 필요하다 (예를 들어, 독시사이클린의 첨가 전). 충분한 양의 TetR이 포유동물 세포에 생산되지 않으면, 세포는 이르게 잠재적 세포독성 AAV-패키징 핵산을 전사하고 번역할 수 있다.
추가 구현예에서, 포유동물 세포는 TetR 및/또는 TetR-KRAB 억제자 서열 측면에 있는 닭 과민성 부위-4 (cHS4)를 암호화하는 하나 이상의 핵산의 안정한 발현을 추가로 포함한다. 본원에 기술된 바와 같이, TetR 및/또는 TetR-KRAB 억제자 서열 측면에 있는 cHS4 서열의 발현은 TetR 발현의 침묵을 방지하고 포유동물 세포 게놈에서 통합된 억제자의 안정성을 추가로 개선한다.
추가 구현예에서, 처리는 탈억제 가능한 프로모터의 억제를 제거하기 위해 독시사이클린으로 처리하는 것을 포함한다.
추가 구현예에서, 각각의 제1, 제2 및 제3 핵산은 트랜스포존-특이적 역위 말단 반복 (ITR)이 측면에 있다.
추가 구현예에서, 아데노 관련 바이러스 (AAV)를 생산하는 방법은 포유동물 세포를 TetR 및/또는 TetR-KRAB 억제자를 암호화하는 핵산, TetR 및/또는 TetR-KRAB 억제자 측면에 있는 닭 과민성 부위-4 (cHS4) 서열, 및 선별 유전자로 안정적으로 형질 감염시키는 것은 하기 단계를 포함한다; 안정적으로 형질감염된 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에, E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자를 암호화하는 제2 핵산, 및 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산으로 형질 감염시키는 단계; 포유동물 세포를 TetR 의 결합 파트너로 처리하는 단계; 제1, 제2 및 제3 탈억제 가능한 프로모터로 활성화하는 단계; AAV를 생산하는 단계; 및 AAV를 수확하는 단계.
일부 구현예에서, 포유동물 세포는 선별 유전자, 예를 들어 제오신 내성 유전자를 추가로 포함한다. 추가 선별 유전자는 다른 항생제 내성 유전자, 예를 들어 카나마이신 및 게네티신 내성 유전자를 포함한다. 본원에 기술된 바와 같이, 제오신 내성 유전자의 발현은 포유동물 세포 게놈에서 정확하게 통합된 억제자의 효율적인 선택을 허용한다.
추가 예시적인 구현예
구현예 1은 제1 탈억제 가능한 프로모터의 제어하에 바이러스 헬퍼 유전자를 암호화하는 핵산 분자, 제2 탈억제 가능한 프로모터의 제어하에 AAV 유전자를 암호화하는 핵산 분자, 및 제1 및 제2 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 핵산 분자를 포함하는, 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포이다.
구현예 2는 구현예 1의 포유동물 세포를 포함하고, 여기서 포유동물 세포는 포유동물 세포 배양물이다.
구현예 3은 구현예 2의 포유동물 세포를 포함하고, 여기서 포유동물 세포 배양물은 현탁 배양물이다.
구현예 4는 구현예 1-3 중 어느 하나의 포유동물 세포를 포함하고, 여기서 바이러스 헬퍼 유전자는 아데노바이러스 헬퍼 유전자이다.
구현예 5는 구현예 4의 포유동물 세포를 포함하고, 여기서 아데노바이러스 헬퍼 유전자는 E2A 및 E4Orf6 유전자를 포함한다.
구현예 6은 구현예 5의 포유동물 세포를 포함하고, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함한다.
구현예 7은 구현예 1-6 중 어느 하나의 포유동물 세포를 포함하고, 여기서 AAV 유전자는 Rep 및 Cap 유전자를 포함한다.
구현예 8은 구현예 7의 포유동물 세포를 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제3 탈억제 가능한 프로모터의 제어하에 있다.
구현예 9는 구현예 7의 포유동물 세포를 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제3 탈억제 가능한 프로모터의 제어하에 있다.
구현예 10은 구현예 8 또는 9 중 어느 하나의 포유동물 세포를 포함하고, 여기서 Cap 유전자는 고유 프로모터의 제어하에 있다.
구현예 11은 구현예 1-10 중 어느 하나의 포유동물 세포를 포함하고, 여기서 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다.
구현예 12는 구현예 11의 포유동물 세포를 포함하고, 여기서 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다.
구현예 13은 구현예 1-12 중 어느 하나의 포유동물 세포를 포함하고, 여기서 억제자 요소는 구성적 프로모터의 제어하에 있다.
구현예 14는 구현예 1-13 중 어느 하나의 포유동물 세포를 포함하고, 여기서 억제자 요소는 테트라사이클린 억제자 단백질이다.
구현예 15는 구현예 14의 포유동물 세포를 포함하고, 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함한다.
구현예 16은 구현예 1-15 중 어느 하나의 포유동물 세포를 포함하고, 여기서 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포이다.
구현예 17은 구현예 1-15 중 어느 하나의 포유동물 세포를 포함하고, 여기서 포유동물 세포는 인간 세포이다.
구현예 18은 구현예 17의 포유동물 세포를 포함하고, 여기서 인간 세포는 인간 배아 신장 (HEK) 세포이다.
구현예 19는 구현예 1-18 중 어느 하나의 포유동물 세포를 포함하고, 2개의 역위 말단 반복 (ITR) 서열을 포함하는 핵산 분자를 추가로 포함한다.
구현예 20은 구현예 1-19 중 어느 하나의 포유동물 세포를 포함하고, 관심 유전자를 암호화하는 핵산 분자를 추가로 포함한다.
구현예 21은 구현예 1-20 중 어느 하나의 포유동물 세포를 포함하고, 제4 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA를 암호화하는 핵산을 추가로 포함한다.
구현예 22는 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 핵산 분자를 포함하는 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포이다.
구현예 23은 구현예 22의 포유동물 세포를 포함하고, 여기서 포유동물 세포는 포유동물 세포 배양물이다.
구현예 24는 구현예 23의 포유동물 세포를 포함하고, 여기서 포유동물 세포 배양물은 현탁 배양물이다.
구현예 25는 구현예 22-24 중 어느 하나의 포유동물 세포를 포함하고, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함한다.
구현예 26은 구현예 22-25 중 어느 하나의 포유동물 세포를 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 27은 구현예 22-25 중 어느 하나의 포유동물 세포를 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 28은 구현예 26 또는 27 중 어느 하나의 포유동물 세포를 포함하고, 여기서 Cap 유전자는 고유 프로모터의 제어하에 있다.
구현예 29는 구현예 22-28 중 어느 하나의 포유동물 세포를 포함하고, 여기서 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다.
구현예 30은 구현예 29의 포유동물 세포를 포함하고, 여기서 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다.
구현예 31은 구현예 22-30 중 어느 하나의 포유동물 세포를 포함하고, 여기서 억제자 요소는 구성적 프로모터의 제어하에 있다.
구현예 32는 구현예 22-31 중 어느 하나의 포유동물 세포를 포함하고, 여기서 억제자 요소는 테트라사이클린 억제자 단백질이다.
구현예 33은 구현예 25의 포유동물 세포를 포함하고, 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함한다.
구현예 34는 구현예 22-33 중 어느 하나의 포유동물 세포를 포함하고, 여기서 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포이다.
구현예 35는 구현예 22-33 중 어느 하나의 포유동물 세포를 포함하고, 여기서 포유동물 세포는 인간 세포이다.
구현예 36은 구현예 35의 포유동물 세포를 포함하고, 여기서 인간 세포는 인간 배아 신장 (HEK) 세포이다.
구현예 37은 구현예 22-36 중 어느 하나의 포유동물 세포를 포함하고, 관심 유전자를 암호화하는 핵산 분자를 추가로 포함한다.
구현예 38은 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 단리된 핵산 분자이다.
구현예 39는 구현예 38의 단리된 핵산을 포함하고, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함한다.
구현예 40은 구현예 38-39 중 하나의 단리된 핵산을 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 41은 구현예 38-39 중 하나의 단리된 핵산을 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 42는 구현예 40 또는 41 중 하나의 단리된 핵산을 포함하고, 여기서 Cap 유전자는 고유 프로모터의 제어하에 있다.
구현예 43은 구현예 38-42 중 하나의 단리된 핵산을 포함하고, 여기서 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다.
구현예 44는 구현예 43의 단리된 핵산을 포함하고, 여기서 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다.
구현예 45는 구현예 38-44 중 하나의 단리된 핵산을 포함하고, 여기서 억제자 요소는 구성적 프로모터의 제어하에 있다.
구현예 46은 구현예 38-45 중 하나의 단리된 핵산을 포함하고, 여기서 억제자 요소는 테트라사이클린 억제자 단백질이다.
구현예 47은 구현예 46의 단리된 핵산을 포함하고, 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함한다.
구현예 48은 구현예 38-47 중 하나의 단리된 핵산을 포함하고, 관심 유전자를 추가로 포함한다.
구현예 49는 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열, 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 단리된 핵산 분자로 형질 감염시키는 단계, 포유동물 세포를 억제자 요소의 결합 파트너로 처리하는 단계, 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화하는 단계, AAV를 생산하는 단계, 및 AAV를 수확하는 단계를 포함하는 포유동물 세포에서 아데노 관련 바이러스 (AAV)를 생산하는 방법이다.
구현예 50은 구현예 49의 방법을 포함하고, 여기서 포유동물 세포는 포유동물 세포 배양물이다.
구현예 51은 구현예 50의 방법을 포함하고, 여기서 포유동물 세포 배양물은 현탁 배양물이다.
구현예 52는 구현예 49-51 중 하나의 방법을 포함하고, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함한다.
구현예 53은 구현예 49-52 중 하나의 방법을 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 54는 구현예 49-52 중 하나의 방법을 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 55는 구현예 54의 방법을 포함하고, 여기서 제4 탈억제 가능한 프로모터는 탈억제 가능한 프로모터를 활성화한 후 AAV를 생산하기 전에 제거된다.
구현예 56은 구현예 53 또는 54 중 하나의 방법을 포함하고, 여기서 Cap 유전자는 고유 프로모터의 제어하에 있다.
구현예 57은 구현예 49-56 중 하나의 방법을 포함하고, 여기서 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다.
구현예 58은 구현예 57의 방법을 포함하고, 여기서 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다.
구현예 59는 구현예 49-58 중 하나의 방법을 포함하고, 여기서 억제자 요소는 구성적 프로모터의 제어하에 있다.
구현예 60은 구현예 49-59 중 하나의 방법을 포함하고, 여기서 억제자 요소는 테트라사이클린 억제자 단백질이다.
구현예 61은 구현예 60의 방법을 포함하고, 여기서 핵산은 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함한다.
구현예 62는 구현예 60 또는 61 중 하나의 방법을 포함하고, 여기서 처리는 독시사이클린을 사용하는 처리를 포함한다.
구현예 63은 구현예 49-62 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포이다.
구현예 64는 구현예 49-63 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 인간 세포이다.
구현예 65는 구현예 64의 방법을 포함하고, 여기서 인간 세포는 인간 배아 신장 (HEK) 세포이다.
구현예 66은 구현예 49-65 중 하나의 방법을 포함하고, 여기서 AAV는 관심 유전자를 암호화하는 핵산 분자를 포함한다.
구현예 67은 구현예 66의 방법을 포함하고, 여기서 AAV는 치료적 관심 유전자를 포함한다.
구현예 68은 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자, 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA, 2개의 역위 말단 반복 (ITR) 서열; 및 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 단리된 핵산 분자로 형질 감염시키는 단계; 포유동물 세포를 억제자 요소의 결합 파트너로 처리하는 단계; 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화하는 단계; AAV를 생산하는 단계; AAV를 수확하는 단계; 및 AAV를 포유동물 환자에 투여하는 단계를 포함하는 아데노 관련 바이러스 (AAV)를 사용하는 치료 방법이다.
구현예 69는 구현예 68의 방법을 포함하고, 여기서 포유동물 세포는 포유동물 세포 배양물이다.
구현예 70은 구현예 69의 방법을 포함하고, 여기서 포유동물 세포 배양물은 현탁 배양물이다.
구현예 71은 구현예 68-70 중 하나의 방법을 포함하고, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함한다.
구현예 72는 구현예 68-71 중 하나의 방법을 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 73은 구현예 68-72 중 하나의 방법을 포함하고, 여기서 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있다.
구현예 74는 구현예 73의 방법을 포함하고, 여기서 제4 탈억제 가능한 프로모터는 탈억제 가능한 프로모터를 활성화한 후 AAV를 생산하기 전 제거된다.
구현예 75는 구현예 73 또는 74 중 하나의 방법을 포함하고, 여기서 Cap 유전자는 고유 프로모터의 제어하에 있다.
구현예 76은 구현예 68-75 중 하나의 방법을 포함하고, 여기서 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다.
구현예 77은 구현예 76의 방법을 포함하고, 여기서 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다.
구현예 78은 구현예 68-77 중 하나의 방법을 포함하고, 여기서 억제자 요소는 구성적 프로모터의 제어하에 있다.
구현예 79는 구현예 68-78 중 하나의 방법을 포함하고, 여기서 억제자 요소는 테트라사이클린 억제자 단백질이다.
구현예 80은 구현예 79의 방법을 포함하고, 여기서 핵산은 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함한다.
구현예 81은 구현예 79 또는 80 중 하나의 방법을 포함하고, 여기서 처리는 독시사이클린을 사용하는 처리를 포함한다.
구현예 82는 구현예 68-81 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포이다.
구현예 83은 구현예 68-82 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 인간 세포이다.
구현예 84는 구현예 83의 방법을 포함하고, 여기서 인간 세포는 인간 배아 신장 (HEK) 세포이다.
구현예 85는 구현예 68-84 중 하나의 방법을 포함하고, 여기서 AAV는 관심 유전자를 암호화하는 핵산 분자를 포함한다.
구현예 86은 구현예 85의 방법을 포함하고, 여기서 AAV는 치료적 관심 유전자를 포함한다.
구현예 87은 구현예 68-86 중 하나의 방법을 포함하고, 여기서 투여는 흡입, 주사 또는 정맥 내 투여를 포함한다.
구현예 88은 하기 단계를 포함하는 아데노 관련 (AAV) 바이러스를 생산하는 방법이다: TetR 및/또는 TetR-KRAB을 암호화하는 하나 이상의 핵산을 안정적으로 발현하는 포유동물 세포를 제1 탈억제 가능한 프로모터의 제어하에 E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산, 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자 암호화하는 제2 핵산, 및, 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산으로 형질 감염시키는 단계; 포유동물 세포를 TetR 및/또는 TetR-KRAB의 결합 파트너로 처리하는 단계; 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화하는 단계; AAV를 생산하는 단계; 및 AAV를 수확하는 단계.
구현예 89는 구현예 88의 방법을 포함하고, 여기서 포유동물 세포는 포유동물 세포 배양물이다.
구현예 90은 구현예 88-89 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포이다.
구현예 91은 구현예 88-90 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 인간 세포이다.
구현예 92는 구현예 91의 방법을 포함하고, 여기서 인간 세포는 인간 배아 신장 (HEK) 세포이다.
구현예 93은 구현예 89의 방법을 포함하고, 여기서 포유동물 세포 배양물은 현탁 배양물이다.
구현예 94는 구현예 88-90 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함한다.
구현예 95는 구현예 88-91 중 하나의 방법을 포함하고, 여기서 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함한다.
구현예 96은 구현예 92의 방법을 포함하고, 여기서 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터이다.
구현예 97은 구현예 88-96 중 하나의 방법을 포함하고, 여기서 안정하게 발현된 TetR 및/또는 TetR-KRAB은 구성적 프로모터의 제어하에 있다.
구현예 98은 구현예 97의 방법을 포함하고, 여기서 TetR-KRAB을 암호화하는 핵산은 TetR과 프레임에 융합된 KRAB을 포함한다.
구현예 99는 구현예 88-98 중 어느 하나의 방법을 포함하고, 여기서 처리는 독시사이클린을 사용하는 처리를 포함한다.
구현예 100은 구현예 88-99 중 어느 하나의 방법을 포함하고, 여기서 각각의 제1, 제2 및 제3 핵산은 트랜스포존-특이적 역위 말단 반복 (ITR)이 측면에 있다.
구현예 101은 구현예 88-100 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 충분한 양의 TetR 및/또는 TetR-KRAB을 발현한다.
구현예 102는 구현예 88-101 중 하나의 방법을 포함하고, 여기서 AAV는 치료적 관심 유전자를 포함한다.
구현예 103은 구현예 88-102 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 TetR 및/또는 TetR-KRAB 억제자 서열 측면에 있는 닭 과민성 부위-4 (cHS4)를 암호화하는 하나 이상의 핵산의 안정한 발현을 추가로 포함한다.
구현예 104는 구현예 88-103 중 하나의 방법을 포함하고, 여기서 포유동물 세포는 제오신 내성 유전자를 추가로 포함한다.
구현예 105는 하기 단계를 포함하는 아데노 관련 바이러스 (AAV)를 생산하는 방법이다: 하기로 포유동물 세포를 안정적으로 형질 감염시키는 단계: TetR 및/또는 TetR-KRAB 억제자를 암호화하는 핵산; TetR 및/또는 TetR-KRAB 억제자 측면에 있는 닭 과민성 부위-4 (cHS4) 서열; 및 선별 유전자; 하기로 안정적으로 형질감염된 포유동물 세포를 형질 감염시키는 단계: 제1 탈억제 가능한 프로모터의 제어하에 E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산; 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자를 암호화하는 제2 핵산; 및 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산; 안정적으로 형질감염된 포유동물 세포를 TetR의 결합 파트너로 처리하는 단계; 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화하는 단계; AAV를 생산하는 단계; 및 AAV를 수확하는 단계.
구현예 106은 구현예 105의 방법을 포함하고, 여기서 안정적으로 형질감염된 포유동물 세포는 충분한 양의 TetR을 생산한다.
구현예 107은 구현예 105 내지 106 중 하나의 방법을 포함하고, 여기서 KRAB 억제자 도메인은 TetR과 프레임에 융합된다.
실시예
실시예 1: 탈억제 가능한 헬퍼 유전자의 설계 및 검증
E2A 및 E4Orf6 유전자의 발현을 유도하기 위해, pcDNA4/TO 벡터 (INVITROGEN)의 탈억제 가능한 프로모터를 활용하였다. 이 프로모터는 TATA 박스와 전사 시작 부위 (TSS) 사이에 2개의 테트라사이클린 작동자 서열 (TetO2)이 삽입된 완전 CMV 프로모터를 포함한다. 테트라사이클린 억제자 단백질 (TetR)의 존재하에, 전사 개시는 TetO2 부위에 대한 TetR의 결합에 의해 차단되었다. 테트라사이클린 또는 독시사이클린이 배지에 첨가될 때, 이는 TetR에 결합하고 그 형태를 변경한다. 이는 TetR의 방출 및 CMV 프로모터의 탈억제/활성화를 야기하고 유도된 유전자 발현을 초래한다 (도 1은 TetR/TetO2 탈억제 가능한 프로모터 시스템의 오프 및 온 형태를 나타냄).
설계를 단순화하고, 안정성을 개선하기 위해, 단일 유도성 CMV 프로모터에 의해 유도되는, 단일 발현 카세트에서 E2A 후 E4Orf6의 번역을 개시하기 위해 내부 리보솜 진입 부위 (IRES) 요소를 사용하였다 (도 1).
VA I 비코딩 RNA를 유도하기 위해, TetO2 삽입을 갖는 H1 프로모터를 적용하였다 (예를 들어, Wiederschain et al., "Single-vector inducible lentiviral RNAi system for oncology target validation, Cell Cycle 8:498-504 (2009) 참조). 유사하게, 독시사이클린의 첨가는 TetR을 방출하고 VA I 발현을 시작하게 한다 (도 1).
언급한 바와 같이, TetR 유전자 발현 카세트는 탈억제 가능한 프로모터의 제어를 위해 포함된다 (도 1 참조). 구성적 인간 PGK 프로모터를 TetR의 발현을 유도하기 위해 사용되고, 이어서 퓨로마이신 N-아세틸트랜스퍼라제의 발현을 지시하는 IRES를 트랜스포존 통합된 세포를 선택하기 위해 사용하였다 (도 2a 참조).
탈억제 가능한 프로모터로부터 잠재적 누출 발현을 줄이기 위해, 향상된 버전의 TetR을 또한 포함하였다 (예를 들어, Szulc et al., "A versatile tool for conditional gene expression and knockdown," Nature Methods 3:109-116 (2006) 참조). 간략하게, KRAB의 강한 억제 도메인을 원래 TetR의 C-말단에 프레임 내 융합시켰고, 이는 그 억제성 활성을 개선하고 유도 전 기저 유전자 발현을 최소화한다. SV40 핵 국소화 신호 (NLS)를 또한 더 큰 TetR-KRAB 융합 단백질의 핵 진입을 촉진하기 위해 삽입하였다 (도 2a, 도 12a-12b).
도 2a에 나타낸 pcDNA3.1-E2A-E4-VA-TetR 벡터의 서열은 하기에 제공된다:
iHelper 1/ pcDNA3.1-E2A-E4-VA-TetR (11, 986 bp)
GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAGAGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGAACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatggccagtcgggaagaggagcagcgcgaaaccacccccgagcgcggacgcggtgcggcgcgacgtcccccaaccatggaggacgtgtcgtccccgtccccgtcgccgccgcctccccgggcgcccccaaaaaagcggatgaggcggcgtatcgagtccgaggacgaggaagactcatcacaagacgcgctggtgccgcgcacacccagcccgcggccatcgacctcggcggcggatttggccattgcgcccaagaagaaaaagaagcgcccttctcccaagcccgagcgcccgccatcaccagaggtaatcgtggacagcgaggaagaaagagaagatgtggcgctacaaatggtgggtttcagcaacccaccggtgctaatcaagcatggcaaaggaggtaagcgcacagtgcggcggctgaatgaagacgacccagtggcgcgtggtatgcggacgcaagaggaagaggaagagcccagcgaagcggaaagtgaaattacggtgatgaacccgctgagtgtgccgatcgtgtctgcgtgggagaagggcatggaggctgcgcgcgcgctgatggacaagtaccacgtggataacgatctaaaggcgaacttcaaactactgcctgaccaagtggaagctctggcggccgtatgcaagacctggctgaacgaggagcaccgcgggttgcagctgaccttcaccagcaacaagacctttgtgacgatgatggggcgattcctgcaggcgtacctgcagtcgtttgcagaggtgacctacaagcatcacgagcccacgggctgcgcgttgtggctgcaccgctgcgctgagatcgaaggcgagcttaagtgtctacacggaagcattatgataaataaggagcacgtgattgaaatggatgtgacgagcgaaaacgggcagcgcgcgctgaaggagcagtctagcaaggccaagatcgtgaagaaccggtggggccgaaatgtggtgcagatctccaacaccgacgcaaggtgctgcgtgcacgacgcggcctgtccggccaatcagttttccggcaagtcttgcggcatgttcttctctgaaggcgcaaaggctcaggtggcttttaagcagatcaaggcttttatgcaggcgctgtatcctaacgcccagaccgggcacggtcaccttttgatgccactacggtgcgagtgcaactcaaagcctgggcacgcgccctttttgggaaggcagctaccaaagttgactccgttcgccctgagcaacgcggaggacctggacgcggatctgatctccgacaagagcgtgctggccagcgtgcaccacccggcgctgatagtgttccagtgctgcaaccctgtgtatcgcaactcgcgcgcgcagggcggaggccccaactgcgacttcaagatatcggcgcccgacctgctaaacgcgttggtgatggtgcgcagcctgtggagtgaaaacttcaccgagctgccgcggatggttgtgcctgagtttaagtggagcactaaacaccagtatcgcaacgtgtccctgccagtggcgcatagcgatgcgcggcagaacccctttgatttttaacccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggaggccaccatgactacgtccggcgttccatttggcatgacactacgaccaacacgatctcggttgtctcggcgcactccgtacagtagggatcgtctacctccttttgagacagaaacccgcgctaccatactggaggatcatccgctgctgcccgaatgtaacactttgacaatgcacaacgtgagttacgtgcgaggtcttccctgcagtgtgggatttacgctgattcaggaatgggttgttccctgggatatggttctaacgcgggaggagcttgtaatcctgaggaagtgtatgcacgtgtgcctgtgttgtgccaacattgatatcatgacgagcatgatgatccatggttacgagtcctgggctctccactgtcattgttccagtcccggttccctgcagtgtatagccggcgggcaggttttggccagctggtttaggatggtggtggatggcgccatgtttaatcagaggtttatatggtaccgggaggtggtgaattacaacatgccaaaagaggtaatgtttatgtccagcgtgtttatgaggggtcgccacttaatctacctgcgcttgtggtatgatggccacgtgggttctgtggtccccgccatgagctttggatacagcgccttgcactgtgggattttgaacaatattgtggtgctgtgctgcagttactgtgctgatttaagtgagatcagggtgcgctgctgtgcccggaggacaaggcgccttatgctgcgggcggtgcgaatcatcgctgaggagaccactgccatgttgtattcctgcaggacggagcggcggcggcagcagtttattcgcgcgctgctgcagcaccaccgccctatcctgatgcacgattatgactctacccccatgtagGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCggggttggggttgcgccttttccaaggcATCCAGCACAGTGGCGGCCGCaatatttgcatgtcgctatgtgttctgggaaatcaccataaacgtgaaatccctatcagtgatagagacttataagttccctatcagtgatagagaaccggtgggcactcttccgtggtctggtggataaattcgcaagggtatcatggcggacgaccggggttcgagccccgtatccggccgtccgccgtgatccatgcggttaccgcccgcgtgtcgaacccaggtgtgcgacgtcagacaacgggggagtgctcctttttgaattccactttggccgcggctcgagggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagggggatctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgaGCCACCatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcCttatatgcactcagcgcCgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggtgctttgtctcctcagcactctgctgtcactcaaggaagtatcatcaagaacaaggagggcatggatgctaagtcactaactgcctggtcccggacactggtgaccttcaaggatgtatttgtggacttcaccagggaggagtggaagctgctggacactgctcagcagatcgtgtacagaaatgtgatgctggagaactataagaacctggtttccttgggttatcagcttactaagccagatgtgatcctccggttggagaagggagaagagccctggctggtggagagagaaattcaccaagagacccatcctgattcagagactgcatttgaaatcaaatcatcagtttaagcgtacagcggctcccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggagGCCACCatgaccgagtacaagcccacggtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgccacaccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaaggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgagatcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggcccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctccccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcggctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgcctgaCCGCGTCTGGAACAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAGCTGACGTCCTTTCCATGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCaAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTC (서열 번호 1)
도 2b에 나타낸 pcDNA3.1-E2A-E4-VA-TetR-V2 벡터의 서열은 하기에 제공된다:
iHelper2/ pcDNA3.1-E2A-E4-VA-TetR-V2 (11, 641 bp)
GACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAGAGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGAACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatggccagtcgggaagaggagcagcgcgaaaccacccccgagcgcggacgcggtgcggcgcgacgtcccccaaccatggaggacgtgtcgtccccgtccccgtcgccgccgcctccccgggcgcccccaaaaaagcggatgaggcggcgtatcgagtccgaggacgaggaagactcatcacaagacgcgctggtgccgcgcacacccagcccgcggccatcgacctcggcggcggatttggccattgcgcccaagaagaaaaagaagcgcccttctcccaagcccgagcgcccgccatcaccagaggtaatcgtggacagcgaggaagaaagagaagatgtggcgctacaaatggtgggtttcagcaacccaccggtgctaatcaagcatggcaaaggaggtaagcgcacagtgcggcggctgaatgaagacgacccagtggcgcgtggtatgcggacgcaagaggaagaggaagagcccagcgaagcggaaagtgaaattacggtgatgaacccgctgagtgtgccgatcgtgtctgcgtgggagaagggcatggaggctgcgcgcgcgctgatggacaagtaccacgtggataacgatctaaaggcgaacttcaaactactgcctgaccaagtggaagctctggcggccgtatgcaagacctggctgaacgaggagcaccgcgggttgcagctgaccttcaccagcaacaagacctttgtgacgatgatggggcgattcctgcaggcgtacctgcagtcgtttgcagaggtgacctacaagcatcacgagcccacgggctgcgcgttgtggctgcaccgctgcgctgagatcgaaggcgagcttaagtgtctacacggaagcattatgataaataaggagcacgtgattgaaatggatgtgacgagcgaaaacgggcagcgcgcgctgaaggagcagtctagcaaggccaagatcgtgaagaaccggtggggccgaaatgtggtgcagatctccaacaccgacgcaaggtgctgcgtgcacgacgcggcctgtccggccaatcagttttccggcaagtcttgcggcatgttcttctctgaaggcgcaaaggctcaggtggcttttaagcagatcaaggcttttatgcaggcgctgtatcctaacgcccagaccgggcacggtcaccttttgatgccactacggtgcgagtgcaactcaaagcctgggcacgcgccctttttgggaaggcagctaccaaagttgactccgttcgccctgagcaacgcggaggacctggacgcggatctgatctccgacaagagcgtgctggccagcgtgcaccacccggcgctgatagtgttccagtgctgcaaccctgtgtatcgcaactcgcgcgcgcagggcggaggccccaactgcgacttcaagatatcggcgcccgacctgctaaacgcgttggtgatggtgcgcagcctgtggagtgaaaacttcaccgagctgccgcggatggttgtgcctgagtttaagtggagcactaaacaccagtatcgcaacgtgtccctgccagtggcgcatagcgatgcgcggcagaacccctttgatttttaacccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggaggccaccatgactacgtccggcgttccatttggcatgacactacgaccaacacgatctcggttgtctcggcgcactccgtacagtagggatcgtctacctccttttgagacagaaacccgcgctaccatactggaggatcatccgctgctgcccgaatgtaacactttgacaatgcacaacgtgagttacgtgcgaggtcttccctgcagtgtgggatttacgctgattcaggaatgggttgttccctgggatatggttctaacgcgggaggagcttgtaatcctgaggaagtgtatgcacgtgtgcctgtgttgtgccaacattgatatcatgacgagcatgatgatccatggttacgagtcctgggctctccactgtcattgttccagtcccggttccctgcagtgtatagccggcgggcaggttttggccagctggtttaggatggtggtggatggcgccatgtttaatcagaggtttatatggtaccgggaggtggtgaattacaacatgccaaaagaggtaatgtttatgtccagcgtgtttatgaggggtcgccacttaatctacctgcgcttgtggtatgatggccacgtgggttctgtggtccccgccatgagctttggatacagcgccttgcactgtgggattttgaacaatattgtggtgctgtgctgcagttactgtgctgatttaagtgagatcagggtgcgctgctgtgcccggaggacaaggcgccttatgctgcgggcggtgcgaatcatcgctgaggagaccactgccatgttgtattcctgcaggacggagcggcggcggcagcagtttattcgcgcgctgctgcagcaccaccgccctatcctgatgcacgattatgactctacccccatgtagGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCggggttggggttgcgccttttccaaggcATCCAGCACAGTGGCGGCCGCaatatttgcatgtcgctatgtgttctgggaaatcaccataaacgtgaaatccctatcagtgatagagacttataagttccctatcagtgatagagaaccggtgggcactcttccgtggtctggtggataaattcgcaagggtatcatggcggacgaccggggttcgagccccgtatccggccgtccgccgtgatccatgcggttaccgcccgcgtgtcgaacccaggtgtgcgacgtcagacaacgggggagtgctcctttttgaattccactttggccgcggctcgagggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagggggatctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgaGCCACCatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcCttatatgcactcagcgcCgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggttcagtttaagcgtacagcggctcccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggagGCCACCatgaccgagtacaagcccacggtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgccacaccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaaggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgagatcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggcccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctccccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcggctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgcctgaCCGCGTCTGGAACAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAGCTGACGTCCTTTCCATGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCaAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTC (서열 번호 2)
탈억제 가능한 헬퍼 (piHelper1) 및 TetR 발현 카세트를 포함하는 전체 전달 플라스미드를 일시적 형질감염에 의한 AAV 생산에서의 사용에 대해 시험하였다. 도 3에 나타낸 바와 같이, 플라스미드가 대조군 pRep-Cap 및 pAAV-GOI 플라스미드로 공동-형질감염될 때, Dox의 첨가는 AAV의 생산을 구성적 헬퍼 유전자 발현을 지원하는 대조군 헬퍼 벡터의 대략 30%의 수준으로 활성화하였다. 따라서, 탈억제 가능한 헬퍼 작제물은 유도 시 AAV 생산에 대해 기능적이었다.
실시예 2: 탈억제 가능한 Rep-Cap 유전자의 설계 및 검증
생산 Rep 단백질을 생산하기 위한 도전은 두 배이다. 우선, Rep78과 Rep52의 비율이 고 역가 AAV 생산을 위해 유도 동안 유지될 필요가 있다. 둘째, Rep52 발현을 위해 필요한 p19 프로모터는 Rep78의 코딩 영역 내에 위치하고, 이는 탈억제 가능한 프로모터를 포함하는데 도전을 생성한다. 이러한 도전을 극복하기 위해, 두 가지 전략이 개발되었다 (도 4a-4c).
우선, Rep 유전자 발현 (도 4a 참조)의 자연 조절을 유지하기 위해, 원래 바이러스 프로모터를 유지하였지만 TATA 박스 및 TSS를 둘러싸는 2개의 TetO 부위를 삽입하여 변형한다. 두 카피의 TetO 부위를 TATA 박스, Rep 결합 요소 (RBE), 및 YY1 부위를 포함하는 코어 요소를 갖는 업스트림 절단된 p5 프로모터 내로 삽입하였다. 게다가, 인핸서로서 역할을 하는, p5 프로모터의 야생형 카피를 Rep 및 Cap 발현을 지원하기 위해 cap 유전자의 다운스트림에 배치하였다 (도 5) (예를 들어, 미국 특허 번호 5,622,856 참조).
도 5에 제시된 탈억제 가능한 p5 프로모터의 서열은 다음과 같다.
min-p5-i1
TATTTAATCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGCCCGAGTGAGCACGCAGGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCC (서열 번호 3)
min-p5-i2
TATTTAAtcTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGATCCCTATCAGTGATAGAGAAGCGGGAGGTTTGAACGCGCAGCCGCC (서열 번호 4)
min-p5-i3
TCCCTATCAGTGATAGAGAtcTATTTAAGCCCGAGTGAGCACGCAGTCCCTATCAGTGATAGAGAGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCC (서열 번호 5)
유사하게, 두 카피의 TetO 부위를 또한 TSS 부위 바로 옆 p19 프로모터 내로 삽입하였다 (도 6). 이러한 삽입의 간섭을 최소화하고 이들 바이러스 프로모터의 원래 활성을 최대화하기 위해, 세 가지 방식의 TetO 부위의 삽입을 최대 성능을 위해 각각의 프로모터에 대해 설계하였다. 따라서, 총 9개의 변형을 조사하였다 (iRepCap1 내지 iRepCap9).
도 6에 개략적으로 도시된 p19를 포함하는 탈억제 가능한 프로모터에 대한 서열은 하기에 제공된다:
p19-i1
ccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtttgaatctcacggag (서열 번호 6)
p19-i2
ccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagTCCCTATCAGTGATAGAGActccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggag (서열 번호 7)
p19-i3
ccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaaTCCCTATCAGTGATAGAGAcagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggag (서열 번호 8)
탈억제 가능한 p19 프로모터의 배치에 대해 2가지 방법을 개발하였다. 제1 방법에서, 탈억제 가능한 p19 프로모터에 의해 유도되는, Rep52에 대한 개별 발현 카세트를 생성하였다. 도 4b에 나타낸 제1 방법에서, Rep78 ORF의 원래 p19 프로모터를 p19 활성을 위해 필요한 3개의 코어 조절 요소에서 6개의 뉴클레오티드를 변경하여 침묵시켰다 (SP1, TATA-1, 및 TATA-2 부위). 이러한 변화는 Rep78 단백질 서열을 변경하지 않았다. Rep78은 탈억제 가능한 p5 프로모터에 의해 제어되었다.
제2 방법에서, 인공 인트론을 Rep78 ORF에서 TetO 부위의 삽입을 위해 생성하였다 (도 4c). 인간 β-글로빈 및 면역글로불린 중쇄 유전자의 인트론 사이 키메라 인트론을 비-필수 내부 서열을 TetO2 부위로 교체하여 채택하였다 (도 7a). 새로운 인공 인트론을 제자리에서 p19 프로모터의 TATA-2의 1bp 또는 25bp 다운스트림에 삽입하였다 (iRepCap-10 및 iRepCap11) (도 4b 및 도 7b). 인접한 TetO-함유 인트론을 갖는 새로운 p19 프로모터는 유도 전 Rep52 유전자 발현의 억제를 보장하면서, mRNA 스플라이싱 동안 인트론의 제거 후 Rep78 단백질의 발현을 여전히 허용한다. 스플라이싱의 효율은 cDNA에 대한 PCR 분석으로 평가한다.
도 7a-7b에 도시된 인트론-기반 p19 프로모터에 대한 핵산 서열은 하기에 제공된다.
In-p19-i1
ccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaaggtaagtTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtactgacatccactttgcctttctctccacagcgcctgtttgaatctcacggag (서열 번호 9)
In-p19-i2
ccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaagcgcctgtttgaatctcacggaaaggtaagtTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtactgacatccactttgcctttctctccacag (서열 번호 10)
11개의 유도성 Rep-Cap 설계의 활성을 시험하기 위해, HEK293 세포를 AAV 생산을 위한 벡터 플러스 표준 pHelper 및 pAAV-GFP 중 하나로 형질감염시켰다. 형질감염 3일 후, 세포를 Rep-Cap 단백질 발현 및 AAV 역가 분석을 위해 수확하였다. 웨스턴 블롯 분석은 다양한 발현 수준의 Rep 및 Cap 단백질을 드러냈고; 다수는 대조군 RepCap 벡터로서 유사한 비율의 Rep78 대 Rep52를 유지하였다 (도 8a). AAV 역가의 qPCR 분석은 설계가 유사하게 수행하거나 대조군 삼중 형질감염에 비해 높은 역가를 가졌음을 나타냈다 (도 8b).
유도성 헬퍼 및 유도성 Rep-Cap 설계 모두의 성능을 시험하기 위해, HEK293 세포를 선택된 iRepCap 벡터, iHelper1/2, 및 pAAV-GFP로 형질감염시키고 3일 동안 처리하지 않고 두거나 독시사이클린으로 처리하였다. 도 9a에 나타낸 바와 같이, Rep 및 Cap의 단백질 발현은 Dox의 첨가, 및 탈억제 가능한 프로모터의 탈억제에 의해서만 유도되었다. 따라서, AAV 역가는 탈억제 시 10 내지 25 배에 걸쳐 유의하게 증가하였다 (도 9b).
iHelper 및 iRepCap을 안정적으로 통합하기 위해, iHelper1/2 및 iRepCap10은 AAV-GFP와 함께 기능 카세트를 단일 PIGGYBAC™ 트랜스포존 전달 벡터 PB007 (Transposagen, Inc., Lexington, KY)로 조립하기 위해 선택되었다. 도 10a-10d는 포유동물 세포, 적절하게 HEK293 세포로의 통합을 위해 사용된 플라스미드 작제물을 나타낸다. 특정 AAV 관심 유전자의 향후 첨가를 용이하게 하기 위해, AAV-GFP를 일부의 전달 벡터에 포함하지 않았다 (도 10a 및 10b). HEK293 세포는 전달 벡터 및 전위효소 mRNA 모두로 형질감염될 것이고 통합된 세포 풀은 퓨로마이신 선택에 의해 풍부해질 것이다. 단일세포 클론은 탈억제를 활성화하는 Dox 처리 유무에 관계없이 AAV 생산을 위해 단리되고 선별될 것이다.
도 10a에 도시된 벡터의 핵산 서열은 하기에 제공된다:
PB007-iHelper1-iRepCap10/ PBBG7 (18, 281 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGAACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatggccagtcgggaagaggagcagcgcgaaaccacccccgagcgcggacgcggtgcggcgcgacgtcccccaaccatggaggacgtgtcgtccccgtccccgtcgccgccgcctccccgggcgcccccaaaaaagcggatgaggcggcgtatcgagtccgaggacgaggaagactcatcacaagacgcgctggtgccgcgcacacccagcccgcggccatcgacctcggcggcggatttggccattgcgcccaagaagaaaaagaagcgcccttctcccaagcccgagcgcccgccatcaccagaggtaatcgtggacagcgaggaagaaagagaagatgtggcgctacaaatggtgggtttcagcaacccaccggtgctaatcaagcatggcaaaggaggtaagcgcacagtgcggcggctgaatgaagacgacccagtggcgcgtggtatgcggacgcaagaggaagaggaagagcccagcgaagcggaaagtgaaattacggtgatgaacccgctgagtgtgccgatcgtgtctgcgtgggagaagggcatggaggctgcgcgcgcgctgatggacaagtaccacgtggataacgatctaaaggcgaacttcaaactactgcctgaccaagtggaagctctggcggccgtatgcaagacctggctgaacgaggagcaccgcgggttgcagctgaccttcaccagcaacaagacctttgtgacgatgatggggcgattcctgcaggcgtacctgcagtcgtttgcagaggtgacctacaagcatcacgagcccacgggctgcgcgttgtggctgcaccgctgcgctgagatcgaaggcgagcttaagtgtctacacggaagcattatgataaataaggagcacgtgattgaaatggatgtgacgagcgaaaacgggcagcgcgcgctgaaggagcagtctagcaaggccaagatcgtgaagaaccggtggggccgaaatgtggtgcagatctccaacaccgacgcaaggtgctgcgtgcacgacgcggcctgtccggccaatcagttttccggcaagtcttgcggcatgttcttctctgaaggcgcaaaggctcaggtggcttttaagcagatcaaggcttttatgcaggcgctgtatcctaacgcccagaccgggcacggtcaccttttgatgccactacggtgcgagtgcaactcaaagcctgggcacgcgccctttttgggaaggcagctaccaaagttgactccgttcgccctgagcaacgcggaggacctggacgcggatctgatctccgacaagagcgtgctggccagcgtgcaccacccggcgctgatagtgttccagtgctgcaaccctgtgtatcgcaactcgcgcgcgcagggcggaggccccaactgcgacttcaagatatcggcgcccgacctgctaaacgcgttggtgatggtgcgcagcctgtggagtgaaaacttcaccgagctgccgcggatggttgtgcctgagtttaagtggagcactaaacaccagtatcgcaacgtgtccctgccagtggcgcatagcgatgcgcggcagaacccctttgatttttaacccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggaggccaccatgactacgtccggcgttccatttggcatgacactacgaccaacacgatctcggttgtctcggcgcactccgtacagtagggatcgtctacctccttttgagacagaaacccgcgctaccatactggaggatcatccgctgctgcccgaatgtaacactttgacaatgcacaacgtgagttacgtgcgaggtcttccctgcagtgtgggatttacgctgattcaggaatgggttgttccctgggatatggttctaacgcgggaggagcttgtaatcctgaggaagtgtatgcacgtgtgcctgtgttgtgccaacattgatatcatgacgagcatgatgatccatggttacgagtcctgggctctccactgtcattgttccagtcccggttccctgcagtgtatagccggcgggcaggttttggccagctggtttaggatggtggtggatggcgccatgtttaatcagaggtttatatggtaccgggaggtggtgaattacaacatgccaaaagaggtaatgtttatgtccagcgtgtttatgaggggtcgccacttaatctacctgcgcttgtggtatgatggccacgtgggttctgtggtccccgccatgagctttggatacagcgccttgcactgtgggattttgaacaatattgtggtgctgtgctgcagttactgtgctgatttaagtgagatcagggtgcgctgctgtgcccggaggacaaggcgccttatgctgcgggcggtgcgaatcatcgctgaggagaccactgccatgttgtattcctgcaggacggagcggcggcggcagcagtttattcgcgcgctgctgcagcaccaccgccctatcctgatgcacgattatgactctacccccatgtagGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCggggttggggttgcgccttttccaaggcATCCAGCACAGTGGCGGCCGCaatatttgcatgtcgctatgtgttctgggaaatcaccataaacgtgaaatccctatcagtgatagagacttataagttccctatcagtgatagagaaccggtgggcactcttccgtggtctggtggataaattcgcaagggtatcatggcggacgaccggggttcgagccccgtatccggccgtccgccgtgatccatgcggttaccgcccgcgtgtcgaacccaggtgtgcgacgtcagacaacgggggagtgctcctttttgaattccactttggccgcggctcgagggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagggggatctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgaGCCACCatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcCttatatgcactcagcgcCgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggtgctttgtctcctcagcactctgctgtcactcaaggaagtatcatcaagaacaaggagggcatggatgctaagtcactaactgcctggtcccggacactggtgaccttcaaggatgtatttgtggacttcaccagggaggagtggaagctgctggacactgctcagcagatcgtgtacagaaatgtgatgctggagaactataagaacctggtttccttgggttatcagcttactaagccagatgtgatcctccggttggagaagggagaagagccctggctggtggagagagaaattcaccaagagacccatcctgattcagagactgcatttgaaatcaaatcatcagtttaagcgtacagcggctcccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggagGCCACCatgaccgagtacaagcccacggtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgccacaccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaaggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgagatcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggcccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctccccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcggctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgcctgaCCGCGTCTGGAACAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAGCTGACGTCCTTTCCATGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCaAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTAGCtGATcaATTgGCGCGCCGAATTCGTTatctgcagaattcggcttggcggctgcgcgttcaaacctcccgcttcaaaatggagaccctgcgtgctcactcgggcttaaatacccagcgtgaccacatggtgtcgcaaaatgtcgcaaaacactcacgtgacctctaatacaggacctctagagcatggaaactagataagaaagaaatacgcagagaccaaagttcaactgaaacgaattaaacggtttattgattaacaagcaaactagtttacagattacgggtgaggtaacgggtgccgatggggcgaggctcagaataaacgccatttgtgtcaacagcaaagtccacatttgtagatttgttgtagttggaagtgtattgaatctctgggttccagcgtttgctgttttctttctgcagctcccattcaatttccacgctgacctgtccggtgctgtactgcgtgatgaacgacgcaaacttagctggactgaaggtagttggaggattcgcgggaacaggtgtattcttaatcaggatctgaggaggcgggtgtttcagtccaaagcctcccatcagcggcgagggatgaaagtgtccgtccgtgtgaggaatcttggcccagataggaccctgcaggtacacgtcccggtcctgccagaccatgccaggtaaggctccttgactgttgacggtccctgtagcaggagcggtgttggccgattgcaggttagtggccaccgtgccgtactcttctgtggccactgggttggtggttttaatttcttcctcgttggttatcataacgttgtcaaggtccacgttgctatttccagctccctgtttcccaaatattaagactccgctcatcggaaaaaatttgtcttcgtcgtccttgtgggttgccatagcgggaccgggatttaccagagagtctctgccattcagatgatacttggtggcaccggtccaggcaaagttgctgttgttattttgattggttgtcttggagacgcgttgctgccggtagcagggcccgggtagccagtttttggcctgattcgccatgctactaggcccggcctgagaaaattgcaacgtccgatttcctgcggtaccactcgtggtctgagtccgagacaggtagtacaggtactggtcgatgagggggttcatcagccggtccaggctttggctgtgcgcgtagctgctgtgaaaaggcacgtcctcaaacgtgtagctgaactgaaagttgttgcccgttctcagcatttgagaaggaaagtattccaggcagtagaaggaggaacggcccacggcctgactgccattgttcagagtcaggtacccgtactgaggaatcatgaagacgtccgccgggaacggaggcaggcagccctggtgcgcagagccgaggacgtacgggagctggtattccgagtccgtaaagacctgaaccgtgctggtaaggttattggcgatggtcgtggtgccatcattcgtcgtgacctccttgacctggatgttgaagagcttgaagttgagcttcttgggccggaatccccagttgttgttgatgagtcgctgccagtcacgtggtgagaagtggcagtggaatctgttaaagtcaaaatacccccagggggtgctgtagccgaagtaggtgttgtcgttggtgctgcctcccgattggctggagatttgcttgtagaggtggttgttgtaggtggggagggcccaggttcgggtgctggtggtgatgactctgtcgcccagccatgtggaatcgcaatgccaatttcctgaggcgttacccactccgtcggcgccttcgttattgtctgccattggagcgccaccgcctgcagccattgtattagatcccacaccagagggggctgcggggggttctccgagtggttgagggtcgggcactgactctgagtcgccagtctgcccaaagttgagtctctttctcgcgggctgctggcctttcttgccgatgcccgaagaggagtctggttcctggggtgattgctctaccggtctcttctttccaggagccgtcttagcgccttcctcaaccagaccgagaggttcgagaacccgcttcttggcctggaagactgctcgcccgaggttgcccccaaaagacgtatcttcttgcagacgctcctgaaactcggcgtcggcgtggttataccgcaggtacggattgtcacccgctttgagctgctggtcgtaggccttgtcgtgctcgagggccgctgcgtccgccgcgttgacgggctcccccttgtcgagtccgttgaagggtccgaggtacttgtagccaggaagcaccagaccccggccgtcgtcctgcttttgctggttggctttgggtttcggggctccaggtttcaagtcccaccactcgcgaatgccctcagagaggttgtcctcgagccaatctggaagataaccatcggcagccatacctgatttaaatcatttattgttcaaagatgcagtcatccaaatccacattgaccagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaacgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcattgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcgtctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttcccaaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgtcaatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggtcttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcgggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaggcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacctggctgaagtttttgatctgatcaccggcgcatcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagatgctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgctgtggagagaaaggcaaagtggatgtcagtaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAacttaccttaaatactgttccatattagtccacgcccactggagctcaggctgggttttggggagcaagtaattggggatgtagcactcatccaccaccttgttcccgcctccggcgccatttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaaccatggatttcaccccggtggtttccacgagcacgtgcatgtggaagtagctctctcccttctcaaattgcacaaagaaaagagcctccggggccttactcacacggcgccattccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcagatccatgtcagaatctggcggcaactcccattccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtcaaggtcgctggggaccttaatcacaatctcgtaaaaccccggcatGGCGGCTGCGCGTTCAAACCTCCCGCTTCAAAATGGAGACCCTGCGTGCTCACTCGGGCgaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAgaTTAAATAgaatggCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 11)
도 10b에 도시된 벡터의 서열은 하기에 제공된다.
PB007-iHelper2-iRepCap10/ PBBG8 (17, 936 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGAACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatggccagtcgggaagaggagcagcgcgaaaccacccccgagcgcggacgcggtgcggcgcgacgtcccccaaccatggaggacgtgtcgtccccgtccccgtcgccgccgcctccccgggcgcccccaaaaaagcggatgaggcggcgtatcgagtccgaggacgaggaagactcatcacaagacgcgctggtgccgcgcacacccagcccgcggccatcgacctcggcggcggatttggccattgcgcccaagaagaaaaagaagcgcccttctcccaagcccgagcgcccgccatcaccagaggtaatcgtggacagcgaggaagaaagagaagatgtggcgctacaaatggtgggtttcagcaacccaccggtgctaatcaagcatggcaaaggaggtaagcgcacagtgcggcggctgaatgaagacgacccagtggcgcgtggtatgcggacgcaagaggaagaggaagagcccagcgaagcggaaagtgaaattacggtgatgaacccgctgagtgtgccgatcgtgtctgcgtgggagaagggcatggaggctgcgcgcgcgctgatggacaagtaccacgtggataacgatctaaaggcgaacttcaaactactgcctgaccaagtggaagctctggcggccgtatgcaagacctggctgaacgaggagcaccgcgggttgcagctgaccttcaccagcaacaagacctttgtgacgatgatggggcgattcctgcaggcgtacctgcagtcgtttgcagaggtgacctacaagcatcacgagcccacgggctgcgcgttgtggctgcaccgctgcgctgagatcgaaggcgagcttaagtgtctacacggaagcattatgataaataaggagcacgtgattgaaatggatgtgacgagcgaaaacgggcagcgcgcgctgaaggagcagtctagcaaggccaagatcgtgaagaaccggtggggccgaaatgtggtgcagatctccaacaccgacgcaaggtgctgcgtgcacgacgcggcctgtccggccaatcagttttccggcaagtcttgcggcatgttcttctctgaaggcgcaaaggctcaggtggcttttaagcagatcaaggcttttatgcaggcgctgtatcctaacgcccagaccgggcacggtcaccttttgatgccactacggtgcgagtgcaactcaaagcctgggcacgcgccctttttgggaaggcagctaccaaagttgactccgttcgccctgagcaacgcggaggacctggacgcggatctgatctccgacaagagcgtgctggccagcgtgcaccacccggcgctgatagtgttccagtgctgcaaccctgtgtatcgcaactcgcgcgcgcagggcggaggccccaactgcgacttcaagatatcggcgcccgacctgctaaacgcgttggtgatggtgcgcagcctgtggagtgaaaacttcaccgagctgccgcggatggttgtgcctgagtttaagtggagcactaaacaccagtatcgcaacgtgtccctgccagtggcgcatagcgatgcgcggcagaacccctttgatttttaacccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggaggccaccatgactacgtccggcgttccatttggcatgacactacgaccaacacgatctcggttgtctcggcgcactccgtacagtagggatcgtctacctccttttgagacagaaacccgcgctaccatactggaggatcatccgctgctgcccgaatgtaacactttgacaatgcacaacgtgagttacgtgcgaggtcttccctgcagtgtgggatttacgctgattcaggaatgggttgttccctgggatatggttctaacgcgggaggagcttgtaatcctgaggaagtgtatgcacgtgtgcctgtgttgtgccaacattgatatcatgacgagcatgatgatccatggttacgagtcctgggctctccactgtcattgttccagtcccggttccctgcagtgtatagccggcgggcaggttttggccagctggtttaggatggtggtggatggcgccatgtttaatcagaggtttatatggtaccgggaggtggtgaattacaacatgccaaaagaggtaatgtttatgtccagcgtgtttatgaggggtcgccacttaatctacctgcgcttgtggtatgatggccacgtgggttctgtggtccccgccatgagctttggatacagcgccttgcactgtgggattttgaacaatattgtggtgctgtgctgcagttactgtgctgatttaagtgagatcagggtgcgctgctgtgcccggaggacaaggcgccttatgctgcgggcggtgcgaatcatcgctgaggagaccactgccatgttgtattcctgcaggacggagcggcggcggcagcagtttattcgcgcgctgctgcagcaccaccgccctatcctgatgcacgattatgactctacccccatgtagGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCggggttggggttgcgccttttccaaggcATCCAGCACAGTGGCGGCCGCaatatttgcatgtcgctatgtgttctgggaaatcaccataaacgtgaaatccctatcagtgatagagacttataagttccctatcagtgatagagaaccggtgggcactcttccgtggtctggtggataaattcgcaagggtatcatggcggacgaccggggttcgagccccgtatccggccgtccgccgtgatccatgcggttaccgcccgcgtgtcgaacccaggtgtgcgacgtcagacaacgggggagtgctcctttttgaattccactttggccgcggctcgagggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagggggatctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgaGCCACCatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcCttatatgcactcagcgcCgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggttcagtttaagcgtacagcggctcccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggagGCCACCatgaccgagtacaagcccacggtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgccacaccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaaggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgagatcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggcccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctccccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcggctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgcctgaCCGCGTCTGGAACAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAGCTGACGTCCTTTCCATGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCaAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTAGCtGATcaATTgGCGCGCCGAATTCGTTatctgcagaattcggcttggcggctgcgcgttcaaacctcccgcttcaaaatggagaccctgcgtgctcactcgggcttaaatacccagcgtgaccacatggtgtcgcaaaatgtcgcaaaacactcacgtgacctctaatacaggacctctagagcatggaaactagataagaaagaaatacgcagagaccaaagttcaactgaaacgaattaaacggtttattgattaacaagcaaactagtttacagattacgggtgaggtaacgggtgccgatggggcgaggctcagaataaacgccatttgtgtcaacagcaaagtccacatttgtagatttgttgtagttggaagtgtattgaatctctgggttccagcgtttgctgttttctttctgcagctcccattcaatttccacgctgacctgtccggtgctgtactgcgtgatgaacgacgcaaacttagctggactgaaggtagttggaggattcgcgggaacaggtgtattcttaatcaggatctgaggaggcgggtgtttcagtccaaagcctcccatcagcggcgagggatgaaagtgtccgtccgtgtgaggaatcttggcccagataggaccctgcaggtacacgtcccggtcctgccagaccatgccaggtaaggctccttgactgttgacggtccctgtagcaggagcggtgttggccgattgcaggttagtggccaccgtgccgtactcttctgtggccactgggttggtggttttaatttcttcctcgttggttatcataacgttgtcaaggtccacgttgctatttccagctccctgtttcccaaatattaagactccgctcatcggaaaaaatttgtcttcgtcgtccttgtgggttgccatagcgggaccgggatttaccagagagtctctgccattcagatgatacttggtggcaccggtccaggcaaagttgctgttgttattttgattggttgtcttggagacgcgttgctgccggtagcagggcccgggtagccagtttttggcctgattcgccatgctactaggcccggcctgagaaaattgcaacgtccgatttcctgcggtaccactcgtggtctgagtccgagacaggtagtacaggtactggtcgatgagggggttcatcagccggtccaggctttggctgtgcgcgtagctgctgtgaaaaggcacgtcctcaaacgtgtagctgaactgaaagttgttgcccgttctcagcatttgagaaggaaagtattccaggcagtagaaggaggaacggcccacggcctgactgccattgttcagagtcaggtacccgtactgaggaatcatgaagacgtccgccgggaacggaggcaggcagccctggtgcgcagagccgaggacgtacgggagctggtattccgagtccgtaaagacctgaaccgtgctggtaaggttattggcgatggtcgtggtgccatcattcgtcgtgacctccttgacctggatgttgaagagcttgaagttgagcttcttgggccggaatccccagttgttgttgatgagtcgctgccagtcacgtggtgagaagtggcagtggaatctgttaaagtcaaaatacccccagggggtgctgtagccgaagtaggtgttgtcgttggtgctgcctcccgattggctggagatttgcttgtagaggtggttgttgtaggtggggagggcccaggttcgggtgctggtggtgatgactctgtcgcccagccatgtggaatcgcaatgccaatttcctgaggcgttacccactccgtcggcgccttcgttattgtctgccattggagcgccaccgcctgcagccattgtattagatcccacaccagagggggctgcggggggttctccgagtggttgagggtcgggcactgactctgagtcgccagtctgcccaaagttgagtctctttctcgcgggctgctggcctttcttgccgatgcccgaagaggagtctggttcctggggtgattgctctaccggtctcttctttccaggagccgtcttagcgccttcctcaaccagaccgagaggttcgagaacccgcttcttggcctggaagactgctcgcccgaggttgcccccaaaagacgtatcttcttgcagacgctcctgaaactcggcgtcggcgtggttataccgcaggtacggattgtcacccgctttgagctgctggtcgtaggccttgtcgtgctcgagggccgctgcgtccgccgcgttgacgggctcccccttgtcgagtccgttgaagggtccgaggtacttgtagccaggaagcaccagaccccggccgtcgtcctgcttttgctggttggctttgggtttcggggctccaggtttcaagtcccaccactcgcgaatgccctcagagaggttgtcctcgagccaatctggaagataaccatcggcagccatacctgatttaaatcatttattgttcaaagatgcagtcatccaaatccacattgaccagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaacgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcattgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcgtctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttcccaaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgtcaatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggtcttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcgggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaggcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacctggctgaagtttttgatctgatcaccggcgcatcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagatgctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgctgtggagagaaaggcaaagtggatgtcagtaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAacttaccttaaatactgttccatattagtccacgcccactggagctcaggctgggttttggggagcaagtaattggggatgtagcactcatccaccaccttgttcccgcctccggcgccatttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaaccatggatttcaccccggtggtttccacgagcacgtgcatgtggaagtagctctctcccttctcaaattgcacaaagaaaagagcctccggggccttactcacacggcgccattccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcagatccatgtcagaatctggcggcaactcccattccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtcaaggtcgctggggaccttaatcacaatctcgtaaaaccccggcatGGCGGCTGCGCGTTCAAACCTCCCGCTTCAAAATGGAGACCCTGCGTGCTCACTCGGGCgaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAgaTTAAATAgaatggCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 12)
도 10c에 제시된 벡터의 서열은 하기에 제공된다.
PB007-iHelper1-iRepCap10-AAV-GFP/ PBBG9 (21, 391 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGAACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatggccagtcgggaagaggagcagcgcgaaaccacccccgagcgcggacgcggtgcggcgcgacgtcccccaaccatggaggacgtgtcgtccccgtccccgtcgccgccgcctccccgggcgcccccaaaaaagcggatgaggcggcgtatcgagtccgaggacgaggaagactcatcacaagacgcgctggtgccgcgcacacccagcccgcggccatcgacctcggcggcggatttggccattgcgcccaagaagaaaaagaagcgcccttctcccaagcccgagcgcccgccatcaccagaggtaatcgtggacagcgaggaagaaagagaagatgtggcgctacaaatggtgggtttcagcaacccaccggtgctaatcaagcatggcaaaggaggtaagcgcacagtgcggcggctgaatgaagacgacccagtggcgcgtggtatgcggacgcaagaggaagaggaagagcccagcgaagcggaaagtgaaattacggtgatgaacccgctgagtgtgccgatcgtgtctgcgtgggagaagggcatggaggctgcgcgcgcgctgatggacaagtaccacgtggataacgatctaaaggcgaacttcaaactactgcctgaccaagtggaagctctggcggccgtatgcaagacctggctgaacgaggagcaccgcgggttgcagctgaccttcaccagcaacaagacctttgtgacgatgatggggcgattcctgcaggcgtacctgcagtcgtttgcagaggtgacctacaagcatcacgagcccacgggctgcgcgttgtggctgcaccgctgcgctgagatcgaaggcgagcttaagtgtctacacggaagcattatgataaataaggagcacgtgattgaaatggatgtgacgagcgaaaacgggcagcgcgcgctgaaggagcagtctagcaaggccaagatcgtgaagaaccggtggggccgaaatgtggtgcagatctccaacaccgacgcaaggtgctgcgtgcacgacgcggcctgtccggccaatcagttttccggcaagtcttgcggcatgttcttctctgaaggcgcaaaggctcaggtggcttttaagcagatcaaggcttttatgcaggcgctgtatcctaacgcccagaccgggcacggtcaccttttgatgccactacggtgcgagtgcaactcaaagcctgggcacgcgccctttttgggaaggcagctaccaaagttgactccgttcgccctgagcaacgcggaggacctggacgcggatctgatctccgacaagagcgtgctggccagcgtgcaccacccggcgctgatagtgttccagtgctgcaaccctgtgtatcgcaactcgcgcgcgcagggcggaggccccaactgcgacttcaagatatcggcgcccgacctgctaaacgcgttggtgatggtgcgcagcctgtggagtgaaaacttcaccgagctgccgcggatggttgtgcctgagtttaagtggagcactaaacaccagtatcgcaacgtgtccctgccagtggcgcatagcgatgcgcggcagaacccctttgatttttaacccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggaggccaccatgactacgtccggcgttccatttggcatgacactacgaccaacacgatctcggttgtctcggcgcactccgtacagtagggatcgtctacctccttttgagacagaaacccgcgctaccatactggaggatcatccgctgctgcccgaatgtaacactttgacaatgcacaacgtgagttacgtgcgaggtcttccctgcagtgtgggatttacgctgattcaggaatgggttgttccctgggatatggttctaacgcgggaggagcttgtaatcctgaggaagtgtatgcacgtgtgcctgtgttgtgccaacattgatatcatgacgagcatgatgatccatggttacgagtcctgggctctccactgtcattgttccagtcccggttccctgcagtgtatagccggcgggcaggttttggccagctggtttaggatggtggtggatggcgccatgtttaatcagaggtttatatggtaccgggaggtggtgaattacaacatgccaaaagaggtaatgtttatgtccagcgtgtttatgaggggtcgccacttaatctacctgcgcttgtggtatgatggccacgtgggttctgtggtccccgccatgagctttggatacagcgccttgcactgtgggattttgaacaatattgtggtgctgtgctgcagttactgtgctgatttaagtgagatcagggtgcgctgctgtgcccggaggacaaggcgccttatgctgcgggcggtgcgaatcatcgctgaggagaccactgccatgttgtattcctgcaggacggagcggcggcggcagcagtttattcgcgcgctgctgcagcaccaccgccctatcctgatgcacgattatgactctacccccatgtagGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCggggttggggttgcgccttttccaaggcATCCAGCACAGTGGCGGCCGCaatatttgcatgtcgctatgtgttctgggaaatcaccataaacgtgaaatccctatcagtgatagagacttataagttccctatcagtgatagagaaccggtgggcactcttccgtggtctggtggataaattcgcaagggtatcatggcggacgaccggggttcgagccccgtatccggccgtccgccgtgatccatgcggttaccgcccgcgtgtcgaacccaggtgtgcgacgtcagacaacgggggagtgctcctttttgaattccactttggccgcggctcgagggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagggggatctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgaGCCACCatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcCttatatgcactcagcgcCgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggtgctttgtctcctcagcactctgctgtcactcaaggaagtatcatcaagaacaaggagggcatggatgctaagtcactaactgcctggtcccggacactggtgaccttcaaggatgtatttgtggacttcaccagggaggagtggaagctgctggacactgctcagcagatcgtgtacagaaatgtgatgctggagaactataagaacctggtttccttgggttatcagcttactaagccagatgtgatcctccggttggagaagggagaagagccctggctggtggagagagaaattcaccaagagacccatcctgattcagagactgcatttgaaatcaaatcatcagtttaagcgtacagcggctcccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggagGCCACCatgaccgagtacaagcccacggtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgccacaccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaaggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgagatcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggcccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctccccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcggctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgcctgaCCGCGTCTGGAACAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAGCTGACGTCCTTTCCATGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCaAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTAGCtGATcaATTgGCGCGCCGAATTCGTTatctgcagaattcggcttggcggctgcgcgttcaaacctcccgcttcaaaatggagaccctgcgtgctcactcgggcttaaatacccagcgtgaccacatggtgtcgcaaaatgtcgcaaaacactcacgtgacctctaatacaggacctctagagcatggaaactagataagaaagaaatacgcagagaccaaagttcaactgaaacgaattaaacggtttattgattaacaagcaaactagtttacagattacgggtgaggtaacgggtgccgatggggcgaggctcagaataaacgccatttgtgtcaacagcaaagtccacatttgtagatttgttgtagttggaagtgtattgaatctctgggttccagcgtttgctgttttctttctgcagctcccattcaatttccacgctgacctgtccggtgctgtactgcgtgatgaacgacgcaaacttagctggactgaaggtagttggaggattcgcgggaacaggtgtattcttaatcaggatctgaggaggcgggtgtttcagtccaaagcctcccatcagcggcgagggatgaaagtgtccgtccgtgtgaggaatcttggcccagataggaccctgcaggtacacgtcccggtcctgccagaccatgccaggtaaggctccttgactgttgacggtccctgtagcaggagcggtgttggccgattgcaggttagtggccaccgtgccgtactcttctgtggccactgggttggtggttttaatttcttcctcgttggttatcataacgttgtcaaggtccacgttgctatttccagctccctgtttcccaaatattaagactccgctcatcggaaaaaatttgtcttcgtcgtccttgtgggttgccatagcgggaccgggatttaccagagagtctctgccattcagatgatacttggtggcaccggtccaggcaaagttgctgttgttattttgattggttgtcttggagacgcgttgctgccggtagcagggcccgggtagccagtttttggcctgattcgccatgctactaggcccggcctgagaaaattgcaacgtccgatttcctgcggtaccactcgtggtctgagtccgagacaggtagtacaggtactggtcgatgagggggttcatcagccggtccaggctttggctgtgcgcgtagctgctgtgaaaaggcacgtcctcaaacgtgtagctgaactgaaagttgttgcccgttctcagcatttgagaaggaaagtattccaggcagtagaaggaggaacggcccacggcctgactgccattgttcagagtcaggtacccgtactgaggaatcatgaagacgtccgccgggaacggaggcaggcagccctggtgcgcagagccgaggacgtacgggagctggtattccgagtccgtaaagacctgaaccgtgctggtaaggttattggcgatggtcgtggtgccatcattcgtcgtgacctccttgacctggatgttgaagagcttgaagttgagcttcttgggccggaatccccagttgttgttgatgagtcgctgccagtcacgtggtgagaagtggcagtggaatctgttaaagtcaaaatacccccagggggtgctgtagccgaagtaggtgttgtcgttggtgctgcctcccgattggctggagatttgcttgtagaggtggttgttgtaggtggggagggcccaggttcgggtgctggtggtgatgactctgtcgcccagccatgtggaatcgcaatgccaatttcctgaggcgttacccactccgtcggcgccttcgttattgtctgccattggagcgccaccgcctgcagccattgtattagatcccacaccagagggggctgcggggggttctccgagtggttgagggtcgggcactgactctgagtcgccagtctgcccaaagttgagtctctttctcgcgggctgctggcctttcttgccgatgcccgaagaggagtctggttcctggggtgattgctctaccggtctcttctttccaggagccgtcttagcgccttcctcaaccagaccgagaggttcgagaacccgcttcttggcctggaagactgctcgcccgaggttgcccccaaaagacgtatcttcttgcagacgctcctgaaactcggcgtcggcgtggttataccgcaggtacggattgtcacccgctttgagctgctggtcgtaggccttgtcgtgctcgagggccgctgcgtccgccgcgttgacgggctcccccttgtcgagtccgttgaagggtccgaggtacttgtagccaggaagcaccagaccccggccgtcgtcctgcttttgctggttggctttgggtttcggggctccaggtttcaagtcccaccactcgcgaatgccctcagagaggttgtcctcgagccaatctggaagataaccatcggcagccatacctgatttaaatcatttattgttcaaagatgcagtcatccaaatccacattgaccagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaacgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcattgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcgtctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttcccaaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgtcaatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggtcttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcgggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaggcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacctggctgaagtttttgatctgatcaccggcgcatcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagatgctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgctgtggagagaaaggcaaagtggatgtcagtaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAacttaccttaaatactgttccatattagtccacgcccactggagctcaggctgggttttggggagcaagtaattggggatgtagcactcatccaccaccttgttcccgcctccggcgccatttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaaccatggatttcaccccggtggtttccacgagcacgtgcatgtggaagtagctctctcccttctcaaattgcacaaagaaaagagcctccggggccttactcacacggcgccattccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcagatccatgtcagaatctggcggcaactcccattccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtcaaggtcgctggggaccttaatcacaatctcgtaaaaccccggcatGGCGGCTGCGCGTTCAAACCTCCCGCTTCAAAATGGAGACCCTGCGTGCTCACTCGGGCgaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAgaTTAAATAgaatggCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTCCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTGGAGCTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGTCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGCGGATTCGAATCCCGGCCGGGAACGGTGCATTGGAACGCGGATTCCCCGTGCCAAGAGTGACGTAAGTACCGCCTATAGAGTCTATAGGCCCACAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTGGGATTCGAACATCGATTGAATTCTGAATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTACTCAGATCTCGAGCTCAAGTAGGGATCCTCTAGAGTCGACCTGCAGAAGCTTGCCTCGAGCAGCGCTGCTCGAGAGATCTACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCgtaGCtGATcaATTgGCGCGCCGAATTCGTTAACAAGCTtTAATTAaCGCgtAcgATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 13)
도 10d에 도시된 벡터의 서열은 하기에 제공된다.
PB007-iHelper2-iRepCap10-AAV-GFP/ PBBG10 (21, 046 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGAACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatggccagtcgggaagaggagcagcgcgaaaccacccccgagcgcggacgcggtgcggcgcgacgtcccccaaccatggaggacgtgtcgtccccgtccccgtcgccgccgcctccccgggcgcccccaaaaaagcggatgaggcggcgtatcgagtccgaggacgaggaagactcatcacaagacgcgctggtgccgcgcacacccagcccgcggccatcgacctcggcggcggatttggccattgcgcccaagaagaaaaagaagcgcccttctcccaagcccgagcgcccgccatcaccagaggtaatcgtggacagcgaggaagaaagagaagatgtggcgctacaaatggtgggtttcagcaacccaccggtgctaatcaagcatggcaaaggaggtaagcgcacagtgcggcggctgaatgaagacgacccagtggcgcgtggtatgcggacgcaagaggaagaggaagagcccagcgaagcggaaagtgaaattacggtgatgaacccgctgagtgtgccgatcgtgtctgcgtgggagaagggcatggaggctgcgcgcgcgctgatggacaagtaccacgtggataacgatctaaaggcgaacttcaaactactgcctgaccaagtggaagctctggcggccgtatgcaagacctggctgaacgaggagcaccgcgggttgcagctgaccttcaccagcaacaagacctttgtgacgatgatggggcgattcctgcaggcgtacctgcagtcgtttgcagaggtgacctacaagcatcacgagcccacgggctgcgcgttgtggctgcaccgctgcgctgagatcgaaggcgagcttaagtgtctacacggaagcattatgataaataaggagcacgtgattgaaatggatgtgacgagcgaaaacgggcagcgcgcgctgaaggagcagtctagcaaggccaagatcgtgaagaaccggtggggccgaaatgtggtgcagatctccaacaccgacgcaaggtgctgcgtgcacgacgcggcctgtccggccaatcagttttccggcaagtcttgcggcatgttcttctctgaaggcgcaaaggctcaggtggcttttaagcagatcaaggcttttatgcaggcgctgtatcctaacgcccagaccgggcacggtcaccttttgatgccactacggtgcgagtgcaactcaaagcctgggcacgcgccctttttgggaaggcagctaccaaagttgactccgttcgccctgagcaacgcggaggacctggacgcggatctgatctccgacaagagcgtgctggccagcgtgcaccacccggcgctgatagtgttccagtgctgcaaccctgtgtatcgcaactcgcgcgcgcagggcggaggccccaactgcgacttcaagatatcggcgcccgacctgctaaacgcgttggtgatggtgcgcagcctgtggagtgaaaacttcaccgagctgccgcggatggttgtgcctgagtttaagtggagcactaaacaccagtatcgcaacgtgtccctgccagtggcgcatagcgatgcgcggcagaacccctttgatttttaacccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggaggccaccatgactacgtccggcgttccatttggcatgacactacgaccaacacgatctcggttgtctcggcgcactccgtacagtagggatcgtctacctccttttgagacagaaacccgcgctaccatactggaggatcatccgctgctgcccgaatgtaacactttgacaatgcacaacgtgagttacgtgcgaggtcttccctgcagtgtgggatttacgctgattcaggaatgggttgttccctgggatatggttctaacgcgggaggagcttgtaatcctgaggaagtgtatgcacgtgtgcctgtgttgtgccaacattgatatcatgacgagcatgatgatccatggttacgagtcctgggctctccactgtcattgttccagtcccggttccctgcagtgtatagccggcgggcaggttttggccagctggtttaggatggtggtggatggcgccatgtttaatcagaggtttatatggtaccgggaggtggtgaattacaacatgccaaaagaggtaatgtttatgtccagcgtgtttatgaggggtcgccacttaatctacctgcgcttgtggtatgatggccacgtgggttctgtggtccccgccatgagctttggatacagcgccttgcactgtgggattttgaacaatattgtggtgctgtgctgcagttactgtgctgatttaagtgagatcagggtgcgctgctgtgcccggaggacaaggcgccttatgctgcgggcggtgcgaatcatcgctgaggagaccactgccatgttgtattcctgcaggacggagcggcggcggcagcagtttattcgcgcgctgctgcagcaccaccgccctatcctgatgcacgattatgactctacccccatgtagGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCggggttggggttgcgccttttccaaggcATCCAGCACAGTGGCGGCCGCaatatttgcatgtcgctatgtgttctgggaaatcaccataaacgtgaaatccctatcagtgatagagacttataagttccctatcagtgatagagaaccggtgggcactcttccgtggtctggtggataaattcgcaagggtatcatggcggacgaccggggttcgagccccgtatccggccgtccgccgtgatccatgcggttaccgcccgcgtgtcgaacccaggtgtgcgacgtcagacaacgggggagtgctcctttttgaattccactttggccgcggctcgagggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagggggatctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgaGCCACCatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcCttatatgcactcagcgcCgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggttcagtttaagcgtacagcggctcccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggagGCCACCatgaccgagtacaagcccacggtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgccacaccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaaggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgagatcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggcccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctccccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcggctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgcctgaCCGCGTCTGGAACAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAGCTGACGTCCTTTCCATGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCaAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTAGCtGATcaATTgGCGCGCCGAATTCGTTatctgcagaattcggcttggcggctgcgcgttcaaacctcccgcttcaaaatggagaccctgcgtgctcactcgggcttaaatacccagcgtgaccacatggtgtcgcaaaatgtcgcaaaacactcacgtgacctctaatacaggacctctagagcatggaaactagataagaaagaaatacgcagagaccaaagttcaactgaaacgaattaaacggtttattgattaacaagcaaactagtttacagattacgggtgaggtaacgggtgccgatggggcgaggctcagaataaacgccatttgtgtcaacagcaaagtccacatttgtagatttgttgtagttggaagtgtattgaatctctgggttccagcgtttgctgttttctttctgcagctcccattcaatttccacgctgacctgtccggtgctgtactgcgtgatgaacgacgcaaacttagctggactgaaggtagttggaggattcgcgggaacaggtgtattcttaatcaggatctgaggaggcgggtgtttcagtccaaagcctcccatcagcggcgagggatgaaagtgtccgtccgtgtgaggaatcttggcccagataggaccctgcaggtacacgtcccggtcctgccagaccatgccaggtaaggctccttgactgttgacggtccctgtagcaggagcggtgttggccgattgcaggttagtggccaccgtgccgtactcttctgtggccactgggttggtggttttaatttcttcctcgttggttatcataacgttgtcaaggtccacgttgctatttccagctccctgtttcccaaatattaagactccgctcatcggaaaaaatttgtcttcgtcgtccttgtgggttgccatagcgggaccgggatttaccagagagtctctgccattcagatgatacttggtggcaccggtccaggcaaagttgctgttgttattttgattggttgtcttggagacgcgttgctgccggtagcagggcccgggtagccagtttttggcctgattcgccatgctactaggcccggcctgagaaaattgcaacgtccgatttcctgcggtaccactcgtggtctgagtccgagacaggtagtacaggtactggtcgatgagggggttcatcagccggtccaggctttggctgtgcgcgtagctgctgtgaaaaggcacgtcctcaaacgtgtagctgaactgaaagttgttgcccgttctcagcatttgagaaggaaagtattccaggcagtagaaggaggaacggcccacggcctgactgccattgttcagagtcaggtacccgtactgaggaatcatgaagacgtccgccgggaacggaggcaggcagccctggtgcgcagagccgaggacgtacgggagctggtattccgagtccgtaaagacctgaaccgtgctggtaaggttattggcgatggtcgtggtgccatcattcgtcgtgacctccttgacctggatgttgaagagcttgaagttgagcttcttgggccggaatccccagttgttgttgatgagtcgctgccagtcacgtggtgagaagtggcagtggaatctgttaaagtcaaaatacccccagggggtgctgtagccgaagtaggtgttgtcgttggtgctgcctcccgattggctggagatttgcttgtagaggtggttgttgtaggtggggagggcccaggttcgggtgctggtggtgatgactctgtcgcccagccatgtggaatcgcaatgccaatttcctgaggcgttacccactccgtcggcgccttcgttattgtctgccattggagcgccaccgcctgcagccattgtattagatcccacaccagagggggctgcggggggttctccgagtggttgagggtcgggcactgactctgagtcgccagtctgcccaaagttgagtctctttctcgcgggctgctggcctttcttgccgatgcccgaagaggagtctggttcctggggtgattgctctaccggtctcttctttccaggagccgtcttagcgccttcctcaaccagaccgagaggttcgagaacccgcttcttggcctggaagactgctcgcccgaggttgcccccaaaagacgtatcttcttgcagacgctcctgaaactcggcgtcggcgtggttataccgcaggtacggattgtcacccgctttgagctgctggtcgtaggccttgtcgtgctcgagggccgctgcgtccgccgcgttgacgggctcccccttgtcgagtccgttgaagggtccgaggtacttgtagccaggaagcaccagaccccggccgtcgtcctgcttttgctggttggctttgggtttcggggctccaggtttcaagtcccaccactcgcgaatgccctcagagaggttgtcctcgagccaatctggaagataaccatcggcagccatacctgatttaaatcatttattgttcaaagatgcagtcatccaaatccacattgaccagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaacgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcattgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcgtctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttcccaaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgtcaatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggtcttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcgggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaggcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacctggctgaagtttttgatctgatcaccggcgcatcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagatgctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgctgtggagagaaaggcaaagtggatgtcagtaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAacttaccttaaatactgttccatattagtccacgcccactggagctcaggctgggttttggggagcaagtaattggggatgtagcactcatccaccaccttgttcccgcctccggcgccatttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaaccatggatttcaccccggtggtttccacgagcacgtgcatgtggaagtagctctctcccttctcaaattgcacaaagaaaagagcctccggggccttactcacacggcgccattccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcagatccatgtcagaatctggcggcaactcccattccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtcaaggtcgctggggaccttaatcacaatctcgtaaaaccccggcatGGCGGCTGCGCGTTCAAACCTCCCGCTTCAAAATGGAGACCCTGCGTGCTCACTCGGGCgaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAgaTTAAATAgaatggCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTCCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTGGAGCTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGTCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGCGGATTCGAATCCCGGCCGGGAACGGTGCATTGGAACGCGGATTCCCCGTGCCAAGAGTGACGTAAGTACCGCCTATAGAGTCTATAGGCCCACAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTGGGATTCGAACATCGATTGAATTCTGAATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTACTCAGATCTCGAGCTCAAGTAGGGATCCTCTAGAGTCGACCTGCAGAAGCTTGCCTCGAGCAGCGCTGCTCGAGAGATCTACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCgtaGCtGATcaATTgGCGCGCCGAATTCGTTAACAAGCTtTAATTAaCGCgtAcgATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 14)
본 발명의 실시에 사용하기 위한 추가 벡터의 서열:
iRepCap1/pKan-Anc80-RepCap-p5i1-p19i1 (10,497 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 15)
iRepCap2/ pKan-Anc80-RepCap-p5i2-p19i1 (10,495 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGATCCCTATCAGTGATAGAGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 16)
iRepCap3/ pKan-Anc80-RepCap-p5i3-p19i1 (10,493 bp)
cctcgaggGCTAGCcattcTCCCTATCAGTGATAGAGAtcTATTTAAGCCCGAGTGAGCACGCAGTCCCTATCAGTGATAGAGAGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 17)
iRepCap4/ pKan-Anc80-RepCap-p5i1-p19i2 (10,495 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagTCCCTATCAGTGATAGAGActccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 18)
iRepCap5/ pKan-Anc80-RepCap-p5i2-p19i2 (10,493 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGATCCCTATCAGTGATAGAGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagTCCCTATCAGTGATAGAGActccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 19)
iRepCap6/ pKan-Anc80-RepCap-p5i3-p19i2 (10,491 bp)
cctcgaggGCTAGCcattcTCCCTATCAGTGATAGAGAtcTATTTAAGCCCGAGTGAGCACGCAGTCCCTATCAGTGATAGAGAGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagTCCCTATCAGTGATAGAGActccagtgggcgtggactaatatggaacagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 20)
iRepCap7/ pKan-Anc80-RepCap-p5i1-p19i3 (10,495 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaaTCCCTATCAGTGATAGAGAcagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 21)
iRepCap8/ pKan-Anc80-RepCap-p5i2-p19i3 (10,493 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGATCCCTATCAGTGATAGAGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaaTCCCTATCAGTGATAGAGAcagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 22)
iRepCap9/ pKan-Anc80-RepCap-p5i3-p19i3 (10,491 bp)
cctcgaggGCTAGCcattcTCCCTATCAGTGATAGAGAtcTATTTAAGCCCGAGTGAGCACGCAGTCCCTATCAGTGATAGAGAGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccaAtgggcAtggacCaaCatggaacagtaCCtCagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatcggggttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACGTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACgccaccATGGCCAAGCCTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTGTGGGAGGGCTAAGCACTTCGTGGCCGAGGAGCAGGACTGACACGTGCTACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTCCTAGGccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaaTCCCTATCAGTGATAGAGAcagtatttaagcgcctgTCCCTATCAGTGATAGAGAtttgaatctcacggagcgtaaacggttggtggcgcagcatctGTTTAAACgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggattcaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaACTAGTTTGCTTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGTATTTCTTTCTTATCTAGTTTCCATGCTCTAGAGTATACgatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 23)
iRepCap10/ pKan-Anc80-인트론-유도성 RepCap (7,567 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaaggtaagtTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtactgacatccactttgcctttctctccacagcgcctgtttgaatctcacggagcgtaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 24)
iRepCap11/ pKan-Anc80-인트론-유도성 RepCap-d2 (7,567 bp)
cctcgaggGCTAGCcattcTATTTAAtcTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtcGCCCGAGTGAGCACGCAGGGTCTCCATTTTGAAGCGGGAGGTTTGAACGCGCAGCCGCCatgccggggttttacgagattgtgattaaggtccccagcgaccttgacgagcatctgcccggcatttctgacagctttgtgaactgggtggccgagaaggaatgggagttgccgccagattctgacatggatctgaatctgattgagcaggcacccctgaccgtggccgagaagctgcagcgcgactttctgacggaatggcgccgtgtgagtaaggccccggaggctcttttctttgtgcaatttgagaagggagagagctacttccacatgcacgtgctcgtggaaaccaccggggtgaaatccatggttttgggacgtttcctgagtcagattcgcgaaaaactgattcagagaatttaccgcgggatcgagccgactttgccaaactggttcgcggtcacaaagaccagaaatggcgccggaggcgggaacaaggtggtggatgagtgctacatccccaattacttgctccccaaaacccagcctgagctccagtgggcgtggactaatatggaacagtatttaagcgcctgtttgaatctcacggaaaggtaagtTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGAtactgacatccactttgcctttctctccacaggaaacggttggtggcgcagcatctgacgcacgtgtcgcagacgcaggagcagaacaaagagaatcagaatcccaattctgatgcgccggtgatcagatcaaaaacttcagccaggtacatggagctggtcgggtggctcgtggacaaggggattacctcggagaagcagtggatccaggaggaccaggcctcatacatctccttcaatgcggcctccaactcgcggtcccaaatcaaggctgccttggacaatgcgggaaagattatgagcctgactaaaaccgcccccgactacctggtgggccagcagcccgtggaggacatttccagcaatcggatttataaaattttggaactaaacgggtacgatccccaatatgcggcttccgtctttctgggatgggccacgaaaaagttcggcaagaggaacaccatctggctgtttgggcctgcaactaccgggaagaccaacatcgcggaggccatagcccacactgtgcccttctacgggtgcgtaaactggaccaatgagaactttcccttcaacgactgtgtcgacaagatggtgatctggtgggaggaggggaagatgaccgccaaggtcgtggagtcggccaaagccattctcggaggaagcaaggtgcgcgtggaccagaaatgcaagtcctcggcccagatagacccgactcccgtgatcgtcacctccaacaccaacatgtgcgccgtgattgacgggaactcaacgaccttcgaacaccagcagccgttgcaagaccggatgttcaaatttgaactcacccgccgtctggatcatgactttgggaaggtcaccaagcaggaagtcaaagactttttccggtgggcaaaggatcacgtggttgaggtggagcatgaattctacgtcaaaaagggtggagccaagaaaagacccgcccccagtgacgcagatataagtgagcccaaacgggtgcgcgagtcagttgcgcagccatcgacgtcagacgcggaagcttcgatcaactacgcagacaggtaccaaaacaaatgttctcgtcacgtgggcatgaatctgatgctgtttccctgcagacaatgcgagagaatgaatcagaattcaaatatctgcttcactcacggacagaaagactgtttagagtgctttcccgtgtcagaatctcaacccgtttctgtcgtcaaaaaggcgtatcagaaactgtgctacattcatcatatcatgggaaaggtgccagacgcttgcactgcctgcgatctggtcaatgtggatttggatgactgcatctttgaacaataaatgatttaaatcaggtatggctgccgatggttatcttccagattggctcgaggacaacctctctgagggcattcgcgagtggtgggacttgaaacctggagccccgaaacccaaagccaaccagcaaaagcaggacgacggccggggtctggtgcttcctggctacaagtacctcggacccttcaacggactcgacaagggggagcccgtcaacgcggcggacgcagcggccctcgagcacgacaaggcctacgaccagcagctcaaagcgggtgacaatccgtacctgcggtataaccacgccgacgccgagtttcaggagcgtctgcaagaagatacgtcttttgggggcaacctcgggcgagcagtcttccaggccaagaagcgggttctcgaacctctcggtctggttgaggaaggcgctaagacggctcctggaaagaagagaccggtagagcaatcaccccaggaaccagactcctcttcgggcatcggcaagaaaggccagcagcccgcgagaaagagactcaactttgggcagactggcgactcagagtcagtgcccgaccctcaaccactcggagaaccccccgcagccccctctggtgtgggatctaatacaatggctgcaggcggtggcgctccaatggcagacaataacgaaggcgccgacggagtgggtaacgcctcaggaaattggcattgcgattccacatggctgggcgacagagtcatcaccaccagcacccgaacctgggccctccccacctacaacaaccacctctacaagcaaatctccagccaatcgggaggcagcaccaacgacaacacctacttcggctacagcaccccctgggggtattttgactttaacagattccactgccacttctcaccacgtgactggcagcgactcatcaacaacaactggggattccggcccaagaagctcaacttcaagctcttcaacatccaggtcaaggaggtcacgacgaatgatggcaccacgaccatcgccaataaccttaccagcacggttcaggtctttacggactcggaataccagctcccgtacgtcctcggctctgcgcaccagggctgcctgcctccgttcccggcggacgtcttcatgattcctcagtacgggtacctgactctgaacaatggcagtcaggccgtgggccgttcctccttctactgcctggaatactttccttctcaaatgctgagaacgggcaacaactttcagttcagctacacgtttgaggacgtgccttttcacagcagctacgcgcacagccaaagcctggaccggctgatgaaccccctcatcgaccagtacctgtactacctgtctcggactcagaccacgagtggtaccgcaggaaatcggacgttgcaattttctcaggccgggcctagtagcatggcgaatcaggccaaaaactggctacccgggccctgctaccggcagcaacgcgtctccaagacaaccaatcaaaataacaacagcaactttgcctggaccggtgccaccaagtatcatctgaatggcagagactctctggtaaatcccggtcccgctatggcaacccacaaggacgacgaagacaaattttttccgatgagcggagtcttaatatttgggaaacagggagctggaaatagcaacgtggaccttgacaacgttatgataaccaacgaggaagaaattaaaaccaccaacccagtggccacagaagagtacggcacggtggccactaacctgcaatcggccaacaccgctcctgctacagggaccgtcaacagtcaaggagccttacctggcatggtctggcaggaccgggacgtgtacctgcagggtcctatctgggccaagattcctcacacggacggacactttcatccctcgccgctgatgggaggctttggactgaaacacccgcctcctcagatcctgattaagaatacacctgttcccgcgaatcctccaactaccttcagtccagctaagtttgcgtcgttcatcacgcagtacagcaccggacaggtcagcgtggaaattgaatgggagctgcagaaagaaaacagcaaacgctggaacccagagattcaatacacttccaactacaacaaatctacaaatgtggactttgctgttgacacaaatggcgtttattctgagcctcgccccatcggcacccgttacctcacccgtaatctgtaaactagtttgcttgttaatcaataaaccgtttaattcgtttcagttgaactttggtctctgcgtatttctttcttatctagtttccatgctctagaggtcctgtattagaggtcacgtgagtgttttgcgacattttgcgacaccatgtggtcacgctgggtatttaagcccgagtgagcacgcagggtctccattttgaagcgggaggtttgaacgcgcagccgccaagccgaattctgcagatatccatcacactggcggccgctcgactagagcggccgccaccgcggtggagctccagcttttgttcgcgcgcttggcgtaatcatggtcatagctgtttcctgtgtgaaattccacagcctggggtgcctaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgactctagtattattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccaaagaatggcaaggtcctggtaacggtctgcgattccgacccgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaagagcttgtgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcatgcgtgattgcgcctgagcaagacgaaatacacgatcgctgttaaaaggacaattacaaacaggaatcgaatgtaaccggcgcaggaacacggccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaaggctgttttcccaggaatcgcggtggtgagtaaccacgcatcatcaggagtacggataaaatgcttgatggtcgggagaggcataaactccgtcagccagttgagacggaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcgtccatgttggagtttaagcgcggacgggagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagctctagtaaaataataaaaaagccggattaataatctggctttttatattctctctctagtatataaacgcagaaaggcccacccgaaggtgagccagtgtgacggcacatttccccgaaaagtgccacctaaattgtaagcgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagaccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggcccactacgtgaaccatcaccctaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaagggagcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaagaaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaaccaccacacccgccgcgcttaatgcgccgctacagggcgcgtcccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgagcgcgcggcgaattgggtaccgggccccc (서열 번호 25)
도 11a에 도시된 PBBG-iHelper-Puro 작제물에 대한 서열은 하기에 나타낸다:
PBBG-iHelper-Puro (11,801 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCCACTAGTCCAGTGTGGTGGAATTCCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGAACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGATAGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatggccagtcgggaagaggagcagcgcgaaaccacccccgagcgcggacgcggtgcggcgcgacgtcccccaaccatggaggacgtgtcgtccccgtccccgtcgccgccgcctccccgggcgcccccaaaaaagcggatgaggcggcgtatcgagtccgaggacgaggaagactcatcacaagacgcgctggtgccgcgcacacccagcccgcggccatcgacctcggcggcggatttggccattgcgcccaagaagaaaaagaagcgcccttctcccaagcccgagcgcccgccatcaccagaggtaatcgtggacagcgaggaagaaagagaagatgtggcgctacaaatggtgggtttcagcaacccaccggtgctaatcaagcatggcaaaggaggtaagcgcacagtgcggcggctgaatgaagacgacccagtggcgcgtggtatgcggacgcaagaggaagaggaagagcccagcgaagcggaaagtgaaattacggtgatgaacccgctgagtgtgccgatcgtgtctgcgtgggagaagggcatggaggctgcgcgcgcgctgatggacaagtaccacgtggataacgatctaaaggcgaacttcaaactactgcctgaccaagtggaagctctggcggccgtatgcaagacctggctgaacgaggagcaccgcgggttgcagctgaccttcaccagcaacaagacctttgtgacgatgatggggcgattcctgcaggcgtacctgcagtcgtttgcagaggtgacctacaagcatcacgagcccacgggctgcgcgttgtggctgcaccgctgcgctgagatcgaaggcgagcttaagtgtctacacggaagcattatgataaataaggagcacgtgattgaaatggatgtgacgagcgaaaacgggcagcgcgcgctgaaggagcagtctagcaaggccaagatcgtgaagaaccggtggggccgaaatgtggtgcagatctccaacaccgacgcaaggtgctgcgtgcacgacgcggcctgtccggccaatcagttttccggcaagtcttgcggcatgttcttctctgaaggcgcaaaggctcaggtggcttttaagcagatcaaggcttttatgcaggcgctgtatcctaacgcccagaccgggcacggtcaccttttgatgccactacggtgcgagtgcaactcaaagcctgggcacgcgccctttttgggaaggcagctaccaaagttgactccgttcgccctgagcaacgcggaggacctggacgcggatctgatctccgacaagagcgtgctggccagcgtgcaccacccggcgctgatagtgttccagtgctgcaaccctgtgtatcgcaactcgcgcgcgcagggcggaggccccaactgcgacttcaagatatcggcgcccgacctgctaaacgcgttggtgatggtgcgcagcctgtggagtgaaaacttcaccgagctgccgcggatggttgtgcctgagtttaagtggagcactaaacaccagtatcgcaacgtgtccctgccagtggcgcatagcgatgcgcggcagaacccctttgatttttaacccgggagttctagggatctgcccctctccctcccccccccctaacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttccaccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacgagcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaaggaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggcagcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacacctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaatggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtatgggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaacgtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgatgataaggatccaccggaggccaccatgactacgtccggcgttccatttggcatgacactacgaccaacacgatctcggttgtctcggcgcactccgtacagtagggatcgtctacctccttttgagacagaaacccgcgctaccatactggaggatcatccgctgctgcccgaatgtaacactttgacaatgcacaacgtgagttacgtgcgaggtcttccctgcagtgtgggatttacgctgattcaggaatgggttgttccctgggatatggttctaacgcgggaggagcttgtaatcctgaggaagtgtatgcacgtgtgcctgtgttgtgccaacattgatatcatgacgagcatgatgatccatggttacgagtcctgggctctccactgtcattgttccagtcccggttccctgcagtgtatagccggcgggcaggttttggccagctggtttaggatggtggtggatggcgccatgtttaatcagaggtttatatggtaccgggaggtggtgaattacaacatgccaaaagaggtaatgtttatgtccagcgtgtttatgaggggtcgccacttaatctacctgcgcttgtggtatgatggccacgtgggttctgtggtccccgccatgagctttggatacagcgccttgcactgtgggattttgaacaatattgtggtgctgtgctgcagttactgtgctgatttaagtgagatcagggtgcgctgctgtgcccggaggacaaggcgccttatgctgcgggcggtgcgaatcatcgctgaggagaccactgccatgttgtattcctgcaggacggagcggcggcggcagcagtttattcgcgcgctgctgcagcaccaccgccctatcctgatgcacgattatgactctacccccatgtagGCGGCCGTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCGGCGCGCCggggtTGAGCTATTCCAGAAGTAGTGAAGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCGGATCGATtggggttgcgccttttccaaggcTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGGGGATCCTCTAGGGCCTCTGAGCTATTCCAGAAGTAGTGAAGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCGGATCGATCGAGCGGATCCAGCACAGTGGCGGCCGCaatatttgcatgtcgctatgtgttctgggaaatcaccataaacgtgaaatccctatcagtgatagagacttataagttccctatcagtgatagagaaccggtgggcactcttccgtggtctggtggataaattcgcaagggtatcatggcggacgaccggggttcgagccccgtatccggccgtccgccgtgatccatgcggttaccgcccgcgtgtcgaacccaggtgtgcgacgtcagacaacgggggagtgctcctttttgaattccactttggccgcggctcgagTGAGCTATTCCAGAAGTAGTGAAGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCGGATCGATGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTGAGCTATTCCAGAAGTAGTGAAGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCGGATCGATCATATATGGCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGCGTTTAAACTTAAGCTTGCCACCatgaccgagtacaagcccacggtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgccacaccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaaggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgagatcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggcccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctccccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcggctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgcctgaAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTAGCtGATgtATAcCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 26)
도 11b에 도시된 PBBG-ITRGFP 작제물에 대한 서열은 하기에 나타낸다:
PBBG-ITRGFP (7,798 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTCCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTGGAGCTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGTCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGCCTCCGCGGATTCGAATCCCGGCCGGGAACGGTGCATTGGAACGCGGATTCCCCGTGCCAAGAGTGACGTAAGTACCGCCTATAGAGTCTATAGGCCCACAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTGGGATTCGAACATCGATTGAATTCTGAATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTACTCAGATCTCGAGCTCAAGTAGGGATCCTCTAGAGTCGACCTGCAGAAGCTTGCCTCGAGCAGCGCTGCTCGAGAGATCTACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCgtaGCtGATcaATTgGCGCGCCGAATTCGTTAACAAGCTtTAATTAaCGCgtATAcCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 27)
도 11c에 도시된 PBBG-iRC8 작제물에 대한 서열은 하기에 나타낸다:
PBBG-iRC8 (9,399 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcTTAagCGCtGATcaATTgGCGCGCCGAATTCGTTatctgcagaattcggcttggcggctgcgcgttcaaacctcccgcttcaaaatggagaccctgcgtgctcactcgggcttaaatacccagcgtgaccacatggtgtcgcaaaatgtcgcaaaacactcacgtgacctctaatacaggacctctagagcatggaaactagataagaaagaaatacgcagagaccaaagttcaactgaaacgaattaaacggtttattgattaacaagcaaactagtttacagattacgggtgaggtaacgggtgccaatggggcggggttcagagtacacgccttctgtattaacagcaaagtccacacttgtagatttgtagtagttggaggtgtactggatctcggggttccagcgcttgctgttttccttctgcagctcccattcaatttccacgctgacctgtccggtgctgtattgcgtgatgaaagagttcagctttgactggttgaaggtggtcggaggatccgcaggtacaggcgtgttcttgatcaggatctgaggcggaggatgtttcaggccaaagccgcccatcagcggagacgggtggaagttgccgtccgtgtgaggaatcttggcccagatgggaccctgcaggtacacgtcccggttctgccagaccataccgggtaaggccccctggctgttgacagttccaatttgaggagccgtgttttgctgctgcaagttatctgccacgataccgtattcctctgtagccacagggttagtggttttgatttcttcctcgctggtgagcatgacatcgctgtaatccgcattgtctctggcagcattttgtttgccaaaaatcaggatcccgttactgggaaaaaaacgctcctcgtcgtctttgtgtgttgccatagcgatgccaggattagccaatgaatttcttccattcagatggtatttggtcccagcagtccaggcaaagttgctattgttgttttgcccggttgtcgttgagacgcgttgttggcggtaacagggtcctggcagccagttctttgcctgattggccattgtattaggcccaccttggctgaagcccagagtctgcgtatttgccgtgcctcctgttgtttgagtccgagacaagtagtacaggtactggtcaatcagaggattcatcagccggtccaagctctggctgtgggcgtagctgctgtggaaaggcacgtcctcgaaggtgtaagtaaactggaagttgttgccggttctcagcatctgcgaaggaaagtattccaggcagtagaaggaggagcgtcccacggcctgactaccgttgttgagtgttaggtagccgtactggggaatcatgaacacgtccgccgggaacggaggcaggcagccctggtgggcagagccgagaacgtacggcagctggtactccgagtccgtaaacacctggatggtgctggtgaggttattggcgatggtcttggtgccttcattctgcgtgacctccttgacctggatgttgaagagcttgaagctgagtctcttgggccggaatccccagttgttgttgatgagtcgctgccagtcacgtggtgaaaagtggcagtggaatctgttaaagtcaaaatacccccagggggtgctgtagccgaagtaggtgttgtcgttggtggctcctcccgatgtcccgttggagatttgcttgtagaggtggttgttgtaggtgggcagggcccaggttcgggtgctggtggtgatgactctgtcgcccagccatgtggaatcgcaatgccaatttcccgaggaactacccactccgtcggcgccttcgttattgtctgccattggtgcgccaccgcctgcagccattgtattaggtcccacaccagagggcgctgctggaggttctccgagaggttgagggtctggaactgactctgagtcgccagtctgaccaaaattgagtctttttctggcgggctgttggcctttcttgccgatgcccgtagaggagtctggagaacgctggggtgatggctctaccggtctcttctttccaggagccgtcttagcgccttcctcaaccagaccgagaggttcgagaacccgcttcttggcctggaagactgctcgcccgaggttgcccccaaaagacgtatcttcttgcagacgctcctgaaactcggcgtcggcgtggttataccgcaggtacggattgtcacccgcctgcagctgctggtcgtaggccttgtcgtgctcgagggccgctgcgtccgccgcgttgacgggctcccccttgtcgagtccgttgaagggtccgaggtacttgtagccaggaagcaccagaccccggccgtcgtcctgcttttgctggttggctttgggcttcggggctccaggtttcagcgcccaccactcgcgaatgccctcagagaggttgtcctcgagccaatctggaagataaccatcggcagccatacctgatttaaatcatttattgttcaaagatgcagtcatccaaatccacattgaccagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaacgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcattgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcgtctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttcccaaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgtcaatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggtcttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcgggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaggcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacctggctgaagtttttgatctgatcaccggcgcatcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagatgctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgctgtggagagaaaggcaaagtggatgtcagtaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAacttaccttaaatactgttccatattagtccacgcccactggagctcaggctgggttttggggagcaagtaattggggatgtagcactcatccaccaccttgttcccgcctccggcgccatttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaaccatggatttcaccccggtggtttccacgagcacgtgcatgtggaagtagctctctcccttctcaaattgcacaaagaaaagagcctccggggccttactcacacggcgccattccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcagatccatgtcagaatctggcggcaactcccattccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtcaaggtcgctggggaccttaatcacaatctcgtaaaaccccggcatGGCGGCTGCGCGTTCAAACCTCCCGCTTCAAAATGGAGACCCTGCGTGCTCACTCGGGCgaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAgaTTAAATAgaatggCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 28)
도 11d에 도시된 PBBG-iRC9 작제물에 대한 서열은 하기에 나타낸다:
PBBG-iRC9 (9,393 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcTTAagCGCtGATcaATTgGCGCGCCGAATTCGTTatctgcagaattcggcttggcggctgcgcgttcaaacctcccgcttcaaaatggagaccctgcgtgctcactcgggcttaaatacccagcgtgaccacatggtgtcgcaaaatgtcgcaaaacactcacgtgacctctaatacaggacctctagagcatggaaactagataagaaagaaatacgcagagaccaaagttcaactgaaacgaattaaacggtttattgattaacaagcaaactagtTTACAGATTACGAGTCAGGTATCTGGTGCCAATGGGGCGGGGTTCACTATATACACCTTCAGTATTAACAGCAAATTCAACATTATTAGACTTGTAATAGTTGGAAGTGTACTGGATCTCCGGGTTCCAGCGCTTGCTGTTTTCCTTCTGCAGCTCCCACTCGATCTCCACGCTGACTTGGCCAGTAGAATACTGGGTGATGAAAGAGTTCAGCTTGTCCTTGTTGAAGGCCGTTGGAGGATCCGCAGGTACAGGTGTGTTTTTGATGAGGATCTGAGGAGGCGGGTGCTTCATTCCAAACCCTCCCATCAGCGGAGAAGGGTGAAAGTTGCCGTCCGTGTGAGGAATTTTGGCCCAAATGGGTCCTTGCAGGTACACATCTCTGTCCTGCCAAACCATACCCGGAAGTATTCCTTGGTTTTGAACCCAGCCGGTCTGCGCCTGTGCTTGGGCACTCTGGTGGTTTGTGGCCACTTGTCCATAGGACTCCGTTGCTACCGGGTTAGTAGTTTTAATTTCTTCTTCGTTGGTTATCATGACTTTGTCCGCATCCACGTTGTCTCTTCCAGTTCCTTGTTTGCCAAAAATTAAAGATCCAGACAAAGGAAAGAAACGGTCCTCTCCTTCTTTGTGGCTGGCCATAGCAGGTCCAGGATTCATCAAGCTATTACGTCCATTGAGAGCCCAAGAAGAAGCTCCAGGCCAAGCAAATTCGCTGTTGTTGTTTTGAGTCACAGTGGTTGAGACACGTTGTTGTCGGTAGCTGGGTCCAGGTATGTAGTTTCTTCCCTGGACAGCCATGTTGCTGGGTCCGGCCACACTGAATTTTAGCGTTTGTTGATTCTGTCCAGAACCGTTAATAGTCTTTGAGAGATAGTACAAGTATTGGTCGATGAGTGGATTCATTAGTCGGTCCAGGCTTTGGCTGTGAGCGTAGCTGCTATGGAAAGGTACGTTCTCAAACTCGTAGCTGAACTGGAAGTTGTTACCCGTTCTTAGCATTTGCGACGGGAAATATTCCAGGCAGTAAAAGGACGAACGACCCACGGCCTGGCTTCCATCATTAAGCGTCAGATACCCGTACTGAGGAATCATGAAAACGTCCGCTGGGAACGGCGGGAGGCAGCCCTCGTGAGCCGACCCGAGCACGTACGGGAGCTGATAGTCTGAGTCCGTGAAGACCTGGACCGTGCTGGTAAGGTTATTGGCGATGGTCTTGACTCCATTGTTGTCCGTAACCTCTTTGACCTGAATGTTGAAGAGCTTGAAGTTGAGTCGCTTAGGCCGGAATCCCCAGTTGTTGTTGATGAGTCGCTGCCAGTCACGTGGTGAGAAGTGGCAGTGGAATCTGTTGAAGTCAAAATACCCCCAGGGGGTGCTGTAGCCGAAGTAGGCGTTGTCATTTGAAGATCCTCCAGATGTGCTGTTGGAGATTTGCTTGTAGAGGTGATTGTTGTAGGTGGGCAGGGCCCAGGTTCGGGTGCTGGTGGTGATGACTCTGTCCCCCAGCCATTGGGAATCGCAATGCCAATTTCCCGAGGAACTACCCACTCCATCGGCACCTTCGTTATTGTCTGCCACTGGTGCGCCACCACCTGAAGCCATTGTAAGAGATCCCACACCTGAGGGGGCTGCGGGAGGTTCTCCGATTGGTTGAGGGTCTGGGACTGACTCTGTGTCGCCAGTCTGACCGAAATTGAGTCTCTTTTTAGCGGGCTGTGCACCCGATTTGCCAATACCCGCGGAGGAGTCCGGTTCCTGAGGAGACTGCTCTACAGGCCTCTTCTTTCCAGGAGCCGTCTTAGCCGCTTCCTCAACCAGACCAAGAGGTTCAAGAAGCCTCTTTTTGGCCTGGAAGACTGCTCGCCCGAGGTTGCCCCCAAAAGACGTATCTTCTTTGAGCCGCTCCTGGAACTCGGCGTCGGCGTGGTTGTACTTGAGGTACGGGTTGTCTCCGGCCTTGAGCTGCTGGTCGTAGGCCTTGTCGTGCTCGAGGGCCGCCGCGTCTGCTGCGTTGACCGGCTCCCCCTTGTCGAGTCCGTTGCCGGGTCCAAGGTATTTGTAACCCGGAAGCACAAGACCTCGAGCGTTGTCTTGATGTTGTTGATTTGCCTTGGGTTGAGGGGCTCCAGGTTTCAAAGCCCACCACTCGCGAATTCCTTCACTAAGGTTGTCCTCGAGCCAATCTGGAAGATAACCATCGGCAGCCATacctgatttaaatcatttattgttcaaagatgcagtcatccaaatccacattgaccagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaacgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcattgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcgtctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttcccaaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgtcaatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggtcttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcgggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaggcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacctggctgaagtttttgatctgatcaccggcgcatcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagatgctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgctgtggagagaaaggcaaagtggatgtcagtaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAacttaccttaaatactgttccatattagtccacgcccactggagctcaggctgggttttggggagcaagtaattggggatgtagcactcatccaccaccttgttcccgcctccggcgccatttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaaccatggatttcaccccggtggtttccacgagcacgtgcatgtggaagtagctctctcccttctcaaattgcacaaagaaaagagcctccggggccttactcacacggcgccattccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcagatccatgtcagaatctggcggcaactcccattccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtcaaggtcgctggggaccttaatcacaatctcgtaaaaccccggcatGGCGGCTGCGCGTTCAAACCTCCCGCTTCAAAATGGAGACCCTGCGTGCTCACTCGGGCgaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAgaTTAAATAgaatggCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 29)
도 11e에 도시된 PBBG-Anc80iRC 작제물에 대한 서열은 하기에 나타낸다:
PBBG-Anc80iRC (9,393 bp)
ACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGCCTCGTTCATTCACGTTTTTGAACCCGTGGAGGACGGGCAGACTCGCGGTGCAAATGTGTTTTACAGCGTGATGGAGCAGATGAAGATGCTCGACACGCTGCAGAACACGCAGCTAGATTAACCCTAGAAAGATAATCATATTGTGACGTACGTTAAAGATAATCATGCGTAAAATTGACGCATGTGTTTTATCGGTCTGTATATCGAGGTTTATTTATTAATTTGAATAGATATTAAGTTTTATTATATTTACACTTACATACTAATAATAAATTCAACAAACAATTTATTTATGTTTATTTATTTATTAAAAAAAAACAAAAACTCAAAATTTCTTCTATAAAGTAACAAAACTTTTATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGGGACAGCCCCCCCCCAAAGCCCCCAGGGATGTAATTACGTCCCTCCCCCGCTAGGGGGCAGCAGCGAGCCGCCCGGGGCTCCGCTCCGGTCCGGCGCTCCCCCCGCATCCCCGAGCCGGCAGCGTGCGGGGACAGCCCGGGCACGGGGAAGGTGGCACGGGATCGCTTTCCTCTGAACGCTTCTCGCTGCTCTTTGAGCCTGCAGACACCTGGGGGGATACGGGGAAAAGGCCTCCAAGGCCAGCTTCCCACAATAAGTTGGGTGAATTTTGGCTCATTCCTCCTTTCTATAGGATTGAGGTCAGAGCTTTGTGATGGGAATTCTGTGGAATGTGTGTCAGTTAGGGTGTGGAAAGTCCCgcGATCgcTAGcTTAagCGCtGATcaATTgGCGCGCCGAATTCGTTatctgcagaattcggcttggcggctgcgcgttcaaacctcccgcttcaaaatggagaccctgcgtgctcactcgggcttaaatacccagcgtgaccacatggtgtcgcaaaatgtcgcaaaacactcacgtgacctctaatacaggacctctagagcatggaaactagataagaaagaaatacgcagagaccaaagttcaactgaaacgaattaaacggtttattgattaacaagcaaactagtttacagattacgggtgaggtaacgggtgccgatggggcgaggctcagaataaacgccatttgtgtcaacagcaaagtccacatttgtagatttgttgtagttggaagtgtattgaatctctgggttccagcgtttgctgttttctttctgcagctcccattcaatttccacgctgacctgtccggtgctgtactgcgtgatgaacgacgcaaacttagctggactgaaggtagttggaggattcgcgggaacaggtgtattcttaatcaggatctgaggaggcgggtgtttcagtccaaagcctcccatcagcggcgagggatgaaagtgtccgtccgtgtgaggaatcttggcccagataggaccctgcaggtacacgtcccggtcctgccagaccatgccaggtaaggctccttgactgttgacggtccctgtagcaggagcggtgttggccgattgcaggttagtggccaccgtgccgtactcttctgtggccactgggttggtggttttaatttcttcctcgttggttatcataacgttgtcaaggtccacgttgctatttccagctccctgtttcccaaatattaagactccgctcatcggaaaaaatttgtcttcgtcgtccttgtgggttgccatagcgggaccgggatttaccagagagtctctgccattcagatgatacttggtggcaccggtccaggcaaagttgctgttgttattttgattggttgtcttggagacgcgttgctgccggtagcagggcccgggtagccagtttttggcctgattcgccatgctactaggcccggcctgagaaaattgcaacgtccgatttcctgcggtaccactcgtggtctgagtccgagacaggtagtacaggtactggtcgatgagggggttcatcagccggtccaggctttggctgtgcgcgtagctgctgtgaaaaggcacgtcctcaaacgtgtagctgaactgaaagttgttgcccgttctcagcatttgagaaggaaagtattccaggcagtagaaggaggaacggcccacggcctgactgccattgttcagagtcaggtacccgtactgaggaatcatgaagacgtccgccgggaacggaggcaggcagccctggtgcgcagagccgaggacgtacgggagctggtattccgagtccgtaaagacctgaaccgtgctggtaaggttattggcgatggtcgtggtgccatcattcgtcgtgacctccttgacctggatgttgaagagcttgaagttgagcttcttgggccggaatccccagttgttgttgatgagtcgctgccagtcacgtggtgagaagtggcagtggaatctgttaaagtcaaaatacccccagggggtgctgtagccgaagtaggtgttgtcgttggtgctgcctcccgattggctggagatttgcttgtagaggtggttgttgtaggtggggagggcccaggttcgggtgctggtggtgatgactctgtcgcccagccatgtggaatcgcaatgccaatttcctgaggcgttacccactccgtcggcgccttcgttattgtctgccattggagcgccaccgcctgcagccattgtattagatcccacaccagagggggctgcggggggttctccgagtggttgagggtcgggcactgactctgagtcgccagtctgcccaaagttgagtctctttctcgcgggctgctggcctttcttgccgatgcccgaagaggagtctggttcctggggtgattgctctaccggtctcttctttccaggagccgtcttagcgccttcctcaaccagaccgagaggttcgagaacccgcttcttggcctggaagactgctcgcccgaggttgcccccaaaagacgtatcttcttgcagacgctcctgaaactcggcgtcggcgtggttataccgcaggtacggattgtcacccgctttgagctgctggtcgtaggccttgtcgtgctcgagggccgctgcgtccgccgcgttgacgggctcccccttgtcgagtccgttgaagggtccgaggtacttgtagccaggaagcaccagaccccggccgtcgtcctgcttttgctggttggctttgggtttcggggctccaggtttcaagtcccaccactcgcgaatgccctcagagaggttgtcctcgagccaatctggaagataaccatcggcagccatacctgatttaaatcatttattgttcaaagatgcagtcatccaaatccacattgaccagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaacgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcattgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcgtctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttcccaaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgtcaatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggtcttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcgggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaggcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacctggctgaagtttttgatctgatcaccggcgcatcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagatgctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgctgtggagagaaaggcaaagtggatgtcagtaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAacttaccttaaatactgttccatattagtccacgcccactggagctcaggctgggttttggggagcaagtaattggggatgtagcactcatccaccaccttgttcccgcctccggcgccatttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaaccatggatttcaccccggtggtttccacgagcacgtgcatgtggaagtagctctctcccttctcaaattgcacaaagaaaagagcctccggggccttactcacacggcgccattccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcagatccatgtcagaatctggcggcaactcccattccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtcaaggtcgctggggaccttaatcacaatctcgtaaaaccccggcatGGCGGCTGCGCGTTCAAACCTCCCGCTTCAAAATGGAGACCCTGCGTGCTCACTCGGGCgaTCTCTATCACTGATAGGGAGATCTCTATCACTGATAGGGAgaTTAAATAgaatggCTAggATCCGGCCGGccTGCAggTGTCCTCACAGGAACGAAGTCCCTAAAGAAACAGTGGCAGCCAGGTTTAGCCCCGGAATTGACTGGATTCCTTTTTTAGGGCCCATTGGTATGGCTTTTTCCCCGTATCCCCCCAGGTGTCTGCAGGCTCAAAGAGCAGCGAGAAGCGTTCAGAGGAAAGCGATCCCGTGCCACCTTCCCCGTGCCCGGGCTGTCCCCGCACGCTGCCGGCTCGGGGATGCGGGGGGAGCGCCGGACCGGAGCGGAGCCCCGGGCGGCTCGCTGCTGCCCCCTAGCGGGGGAGGGACGTAATTACATCCCTGGGGGCTTTGGGGGGGGGCTGTCCCTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTAGATCTTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCTATAACAAGAAAATATATATATAATAAGTTATCACGTAAGTAGAACATGAAATAACAATATAATTATCGTATGAGTTAAATCTTAAAAGTCACGTAAAAGATAATCATGCGTCATTTTGACTCACGCGGTCGTTATAGTTCAAAATCAGTGACACTTACCGCATTGACAAGCACGCCTCACGGGAGCTCCAAGCGGCGACTGAGATGTCCTAAATGCACAGCGACGGATTCGCGCTATTTAGAAAGAGAGAGCAATATTTCAAGAATGCATGCGTCAATTTTACGCAGACTATCTTTCTAGGGTTAATCTAGCTGCATCAGGATCATATCGTCGGGTCTTTTTTCCGGCTCAGTCATCGCCCAAGCTGGCGCTATCTGGGCATCGGGGAGGAAGAAGCCCGTGCCTTTTCCCGCGAGGTTGAAGCGGCATGGAAAGAGTTTGCCGAGGATGACTGCTGCTGCATTGACGTTGAGCGAAAACGCACGTTTACCATGATGATTCGGGAAGGTGTGGCCATGCACGCCTTTAACGGTGAACTGTTCGTTCAGGCCACCTGGGATACCAGTTCGTCGCGGCTTTTCCGGACACAGTTCCGGATGGTCAGCCCGAAGCGCATCAGCAACCCGAACAATACCGGCGACAGCCGGAACTGCCGTGCCGGTGTGCAGATTAATGACAGCGGTGCGGCGCTGGGATATTACGTCAGCGAGGACGGGTATCCTGGCTGGATGCCGCAGAAATGGACATGGATACCCCGTGAGTTACCCGGCGGGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCAT (서열 번호 30)
도 12a에 도시된 pcDNA-TetR-Ins 작제물에 대한 서열은 하기에 나타낸다:
pcDNA-TetR-Ins (7147 bp)
gacggatcgggagatctgagctcacggggacagcccccccccaaagcccccagggatgtaattacgtccctcccccgctagggggcagcagcgagccgcccggggctccgctccggtccggcgctccccccgcatccccgagccggcagcgtgcggggacagcccgggcacggggaaggtggcacgggatcgctttcctctgaacgcttctcgctgctctttgagcctgcagacacctggggggatacggggaaaaagctttaggctgaaagagagatttagaatgacagaatcatagaacggcctgggttgcaaaggagcacagtgctcatccagatccaaccccctgctatgtgcagggtcatcaaccagcagcccaggctgcccagagccacatccagcctggccttgaatgcctgcaggcccgatcccctatggtcgactctcagtacaatctgctctgatgccgcatagttaagccagtatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagcaaaatttaagctacaacaaggcaaggcttgaccgacaattgcatgaagaatctgcttagggttaggcgttttgcgctgcttcgcgatgtacgggccagatatacgcgttgacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagcccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggactatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctctctggctaactagagaacccactgcttactggcttatcgaaattaatacgactcactatagggagacccaagctggctagcgtttaaacttaagctttctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgagccaccatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgccttatatgcactcagcgccgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggttcagtttaagcgtacagcgggatccactagtccagtgtggtggaattctgcagatatccagcacagtggcggccgctcgagtctagagggcccgtttaaacccgctgatcagcctcgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatggcttctgaggcggaaagaaccagctggggctctagggggtatccccacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcggggcatccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgatttataagggattttggggatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaattaattctgtggaatgtgtgtcagttagggtgtggaaagtccccaggctccccaggcaggcagaagtatgcaaagcatgcatctcaattagtcagcaaccaggtgtggaaagtccccaggctccccagcaggcagaagtatgcaaagcatgcatctcaattagtcagcaaccatagtcccgcccctaactccgcccatcccgcccctaactccgcccagttccgcccattctccgccccatggctgactaattttttttatttatgcagaggccgaggccgcctctgcctctgagctattccagaagtagtgaggaggcttttttggaggcctaggcttttgcaaaaagctcccgggagcttgtatatccattttcggatctgatcagcacgtgttgacaattaatcatcggcatagtatatcggcatagtataatacgacaaggtgaggaactaaaccatggccaagttgaccagtgccgttccggtgctcaccgcgcgcgacgtcgccggagcggtcgagttctggaccgaccggctcgggttctcccgggacttcgtggaggacgacttcgccggtgtggtccgggacgacgtgaccctgttcatcagcgcggtccaggaccaggtggtgccggacaacaccctggcctgggtgtgggtgcgcggcctggacgagctgtacgccgagtggtcggaggtcgtgtccacgaacttccgggacgcctccgggccggccatgaccgagatcggcgagcagccgtgggggcgggagttcgccctgcgcgacccggccggcaactgcgtgcacttcgtggccgaggagcaggactgacacgtgctacgagatttcgattccaccgccgccttctatgaaaggttgggcttcggaatcgttttccgggacgccggctggatgatcctccagcgcggggatctcatgctggagttcttcgcccaccccaacttgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatcatgtctgtataccgtcgacctctagctagagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagagagctcacggggacagcccccccccaaagcccccagggatgtaattacgtccctcccccgctagggggcagcagcgagccgcccggggctccgctccggtccggcgctccccccgcatccccgagccggcagcgtgcggggacagcccgggcacggggaaggtggcacgggatcgctttcctctgaacgcttctcgctgctctttgagcctgcagacacctggggggatacggggaaaaagctttaggctgaaagagagatttagaatgacagaatcatagaacggcctgggttgcaaaggagcacagtgctcatccagatccaaccccctgctatgtgcagggtcatcaaccagcagcccaggctgcccagagccacatccagcctggccttgaatgcctgcaggacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcaatgctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtc (서열 번호 31)
도 12b에 도시된 pcDNA-TetR-KRAB-Ins 작제물에 대한 서열은 하기에 나타낸다:
pcDNA-TetR-KRAB-Ins (7493 bp)
gacggatcgggagatctgagctcacggggacagcccccccccaaagcccccagggatgtaattacgtccctcccccgctagggggcagcagcgagccgcccggggctccgctccggtccggcgctccccccgcatccccgagccggcagcgtgcggggacagcccgggcacggggaaggtggcacgggatcgctttcctctgaacgcttctcgctgctctttgagcctgcagacacctggggggatacggggaaaaagctttaggctgaaagagagatttagaatgacagaatcatagaacggcctgggttgcaaaggagcacagtgctcatccagatccaaccccctgctatgtgcagggtcatcaaccagcagcccaggctgcccagagccacatccagcctggccttgaatgcctgcaggcccgatcccctatggtcgactctcagtacaatctgctctgatgccgcatagttaagccagtatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagcaaaatttaagctacaacaaggcaaggcttgaccgacaattgcatgaagaatctgcttagggttaggcgttttgcgctgcttcgcgatgtacgggccagatatacgcgttgacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagcccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggactatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctctctggctaactagagaacccactgcttactggcttatcgaaattaatacgactcactatagggagacccaagctggctagcgtttaaacttaagctttctgtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatggagggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggaccctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttattttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaaattcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggcaatcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatgataaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaacaactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttgagatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttcttctttttcctacagctcctgggcaacgtgctggttattgtgctgtctcatcattttggcaaagaattgtaatacgactcactatagggcgagccaccatggctagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgccttatatgcactcagcgccgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtccccaaaaaagaagagaaaggtcgacggcggtggtgctttgtctcctcagcactctgctgtcactcaaggaagtatcatcaagaacaaggagggcatggatgctaagtcactaactgcctggtcccggacactggtgaccttcaaggatgtatttgtggacttcaccagggaggagtggaagctgctggacactgctcagcagatcgtgtacagaaatgtgatgctggagaactataagaacctggtttccttgggttatcagcttactaagccagatgtgatcctccggttggagaagggagaagagccctggctggtggagagagaaattcaccaagagacccatcctgattcagagactgcatttgaaatcaaatcatcagtttaagcgtacagcggggatccactagtccagtgtggtggaattctgcagatatccagcacagtggcggccgctcgagtctagagggcccgtttaaacccgctgatcagcctcgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatggcttctgaggcggaaagaaccagctggggctctagggggtatccccacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcggggcatccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgatttataagggattttggggatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaattaattctgtggaatgtgtgtcagttagggtgtggaaagtccccaggctccccaggcaggcagaagtatgcaaagcatgcatctcaattagtcagcaaccaggtgtggaaagtccccaggctccccagcaggcagaagtatgcaaagcatgcatctcaattagtcagcaaccatagtcccgcccctaactccgcccatcccgcccctaactccgcccagttccgcccattctccgccccatggctgactaattttttttatttatgcagaggccgaggccgcctctgcctctgagctattccagaagtagtgaggaggcttttttggaggcctaggcttttgcaaaaagctcccgggagcttgtatatccattttcggatctgatcagcacgtgttgacaattaatcatcggcatagtatatcggcatagtataatacgacaaggtgaggaactaaaccatggccaagttgaccagtgccgttccggtgctcaccgcgcgcgacgtcgccggagcggtcgagttctggaccgaccggctcgggttctcccgggacttcgtggaggacgacttcgccggtgtggtccgggacgacgtgaccctgttcatcagcgcggtccaggaccaggtggtgccggacaacaccctggcctgggtgtgggtgcgcggcctggacgagctgtacgccgagtggtcggaggtcgtgtccacgaacttccgggacgcctccgggccggccatgaccgagatcggcgagcagccgtgggggcgggagttcgccctgcgcgacccggccggcaactgcgtgcacttcgtggccgaggagcaggactgacacgtgctacgagatttcgattccaccgccgccttctatgaaaggttgggcttcggaatcgttttccgggacgccggctggatgatcctccagcgcggggatctcatgctggagttcttcgcccaccccaacttgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatcatgtctgtataccgtcgacctctagctagagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagagagctcacggggacagcccccccccaaagcccccagggatgtaattacgtccctcccccgctagggggcagcagcgagccgcccggggctccgctccggtccggcgctccccccgcatccccgagccggcagcgtgcggggacagcccgggcacggggaaggtggcacgggatcgctttcctctgaacgcttctcgctgctctttgagcctgcagacacctggggggatacggggaaaaagctttaggctgaaagagagatttagaatgacagaatcatagaacggcctgggttgcaaaggagcacagtgctcatccagatccaaccccctgctatgtgcagggtcatcaaccagcagcccaggctgcccagagccacatccagcctggccttgaatgcctgcaggacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcaatgctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtc (서열 번호 32)
본원에 기술된 방법 및 응용에 대한 다른 적합한 변형 및 개조가 구현예의 임의의 범위를 벗어나지 않고 이루어질 수 있음이 관련 기술 분야의 당업자에게 쉽게 명백할 것이다.
특정 구현예가 본원에서 도시되고 기술되었지만, 청구 범위는 기술되고 나타낸 부분의 특정 형태 또는 배열에 한정되는 것이 아님이 이해된다. 본 명세서에서, 예시적인 구현예가 개시되어 있고, 특정 용어가 사용되지만, 제한의 목적이 아니라 포괄적이고 설명적인 의미로만 사용된다. 구현예의 변형 및 변이는 상기 교시에 비추어 가능하다. 따라서, 구현예는 구체적으로 기술된 것과 달리 실시될 수 있음이 이해되어야 한다.
본 명세서에서 언급된 모든 간행물, 특허 및 특허 출원은 본원에 각각의 개별 간행물, 특허 또는 특허 출원이 구체적 및 개별적으로 참고로 포함된 것으로 표시된 것과 동일한 범위로 참고로 포함된다.
SEQUENCE LISTING <110> LONZA WALKERSVILLE, INC. <120> ADENO-ASSOCIATED VIRUS (AAV) PRODUCER CELL LINE AND RELATED METHODS <130> 0132-0049WO1 <140> <141> <150> 62/866,092 <151> 2019-06-25 <150> 62/783,589 <151> 2018-12-21 <160> 32 <170> PatentIn version 3.5 <210> 1 <211> 11986 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 1 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgttgacatt 240 gattattgac tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata 300 tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc 360 cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc 420 attgacgtca atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt 480 atcatatgcc aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt 540 atgcccagta catgacctta tgggactttc ctacttggca gtacatctac gtattagtca 600 tcgctattac catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg 660 actcacgggg atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc 720 aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 780 gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca 840 ctgcttactg gcttatcgaa attaatacga ctcactatag ggagacccaa gctggctagc 900 gtttaaactt aagcttggta ccgagctcgg atccactagt ccagtgtggt ggaattcctg 960 cttcgcgatg tacgggccag atatacgcgt tgacattgat tattgactag ttattaatag 1020 taatcaatta cggggtcatt agttcatagc ccatatatgg agttccgcgt tacataactt 1080 acggtaaatg gcccgcctgg ctgaccgccc aacgaccccc gcccattgac gtcaataatg 1140 acgtatgttc ccatagtaac gccaataggg actttccatt gacgtcaatg ggtggagtat 1200 ttacggtaaa ctgcccactt ggcagtacat caagtgtatc atatgccaag tacgccccct 1260 attgacgtca atgacggtaa atggcccgcc tggcattatg cccagtacat gaccttatgg 1320 gactttccta cttggcagta catctacgta ttagtcatcg ctattaccat ggtgatgcgg 1380 ttttggcagt acatcaatgg gcgtggatag cggtttgact cacggggatt tccaagtctc 1440 caccccattg acgtcaatgg gagtttgttt tggaaccaaa atcaacggga ctttccaaaa 1500 tgtcgtaaca actccgcccc attgacgcaa atgggcggta ggcgtgtacg gtgggaggtc 1560 tatataagca gagctctccc tatcagtgat agagatctcc ctatcagtga tagagatcgt 1620 cgacgagctc gtttagtgaa ccgtcagatc gcctggagac gccatccacg ctgttttgac 1680 ctccatagaa gacaccggga ccgatccagc ctccggactc tagcgtttaa acttaagctt 1740 gccaccatgg ccagtcggga agaggagcag cgcgaaacca cccccgagcg cggacgcggt 1800 gcggcgcgac gtcccccaac catggaggac gtgtcgtccc cgtccccgtc gccgccgcct 1860 ccccgggcgc ccccaaaaaa gcggatgagg cggcgtatcg agtccgagga cgaggaagac 1920 tcatcacaag acgcgctggt gccgcgcaca cccagcccgc ggccatcgac ctcggcggcg 1980 gatttggcca ttgcgcccaa gaagaaaaag aagcgccctt ctcccaagcc cgagcgcccg 2040 ccatcaccag aggtaatcgt ggacagcgag gaagaaagag aagatgtggc gctacaaatg 2100 gtgggtttca gcaacccacc ggtgctaatc aagcatggca aaggaggtaa gcgcacagtg 2160 cggcggctga atgaagacga cccagtggcg cgtggtatgc ggacgcaaga ggaagaggaa 2220 gagcccagcg aagcggaaag tgaaattacg gtgatgaacc cgctgagtgt gccgatcgtg 2280 tctgcgtggg agaagggcat ggaggctgcg cgcgcgctga tggacaagta ccacgtggat 2340 aacgatctaa aggcgaactt caaactactg cctgaccaag tggaagctct ggcggccgta 2400 tgcaagacct ggctgaacga ggagcaccgc gggttgcagc tgaccttcac cagcaacaag 2460 acctttgtga cgatgatggg gcgattcctg caggcgtacc tgcagtcgtt tgcagaggtg 2520 acctacaagc atcacgagcc cacgggctgc gcgttgtggc tgcaccgctg cgctgagatc 2580 gaaggcgagc ttaagtgtct acacggaagc attatgataa ataaggagca cgtgattgaa 2640 atggatgtga cgagcgaaaa cgggcagcgc gcgctgaagg agcagtctag caaggccaag 2700 atcgtgaaga accggtgggg ccgaaatgtg gtgcagatct ccaacaccga cgcaaggtgc 2760 tgcgtgcacg acgcggcctg tccggccaat cagttttccg gcaagtcttg cggcatgttc 2820 ttctctgaag gcgcaaaggc tcaggtggct tttaagcaga tcaaggcttt tatgcaggcg 2880 ctgtatccta acgcccagac cgggcacggt caccttttga tgccactacg gtgcgagtgc 2940 aactcaaagc ctgggcacgc gccctttttg ggaaggcagc taccaaagtt gactccgttc 3000 gccctgagca acgcggagga cctggacgcg gatctgatct ccgacaagag cgtgctggcc 3060 agcgtgcacc acccggcgct gatagtgttc cagtgctgca accctgtgta tcgcaactcg 3120 cgcgcgcagg gcggaggccc caactgcgac ttcaagatat cggcgcccga cctgctaaac 3180 gcgttggtga tggtgcgcag cctgtggagt gaaaacttca ccgagctgcc gcggatggtt 3240 gtgcctgagt ttaagtggag cactaaacac cagtatcgca acgtgtccct gccagtggcg 3300 catagcgatg cgcggcagaa cccctttgat ttttaacccg ggagttctag ggatctgccc 3360 ctctccctcc ccccccccta acgttactgg ccgaagccgc ttggaataag gccggtgtgc 3420 gtttgtctat atgttatttt ccaccatatt gccgtctttt ggcaatgtga gggcccggaa 3480 acctggccct gtcttcttga cgagcattcc taggggtctt tcccctctcg ccaaaggaat 3540 gcaaggtctg ttgaatgtcg tgaaggaagc agttcctctg gaagcttctt gaagacaaac 3600 aacgtctgta gcgacccttt gcaggcagcg gaacccccca cctggcgaca ggtgcctctg 3660 cggccaaaag ccacgtgtat aagatacacc tgcaaaggcg gcacaacccc agtgccacgt 3720 tgtgagttgg atagttgtgg aaagagtcaa atggctctcc tcaagcgtat tcaacaaggg 3780 gctgaaggat gcccagaagg taccccattg tatgggatct gatctggggc ctcggtgcac 3840 atgctttaca tgtgtttagt cgaggttaaa aaaacgtcta ggccccccga accacgggga 3900 cgtggttttc ctttgaaaaa cacgatgata aggatccacc ggaggccacc atgactacgt 3960 ccggcgttcc atttggcatg acactacgac caacacgatc tcggttgtct cggcgcactc 4020 cgtacagtag ggatcgtcta cctccttttg agacagaaac ccgcgctacc atactggagg 4080 atcatccgct gctgcccgaa tgtaacactt tgacaatgca caacgtgagt tacgtgcgag 4140 gtcttccctg cagtgtggga tttacgctga ttcaggaatg ggttgttccc tgggatatgg 4200 ttctaacgcg ggaggagctt gtaatcctga ggaagtgtat gcacgtgtgc ctgtgttgtg 4260 ccaacattga tatcatgacg agcatgatga tccatggtta cgagtcctgg gctctccact 4320 gtcattgttc cagtcccggt tccctgcagt gtatagccgg cgggcaggtt ttggccagct 4380 ggtttaggat ggtggtggat ggcgccatgt ttaatcagag gtttatatgg taccgggagg 4440 tggtgaatta caacatgcca aaagaggtaa tgtttatgtc cagcgtgttt atgaggggtc 4500 gccacttaat ctacctgcgc ttgtggtatg atggccacgt gggttctgtg gtccccgcca 4560 tgagctttgg atacagcgcc ttgcactgtg ggattttgaa caatattgtg gtgctgtgct 4620 gcagttactg tgctgattta agtgagatca gggtgcgctg ctgtgcccgg aggacaaggc 4680 gccttatgct gcgggcggtg cgaatcatcg ctgaggagac cactgccatg ttgtattcct 4740 gcaggacgga gcggcggcgg cagcagttta ttcgcgcgct gctgcagcac caccgcccta 4800 tcctgatgca cgattatgac tctaccccca tgtaggcggc cgctcgagtc tagagggccc 4860 gtttaaaccc gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc 4920 ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa 4980 aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 5040 gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 5100 ggctctatgg cttctgaggc ggaaagaacc agctggggct ctagggggta tccccggggt 5160 tggggttgcg ccttttccaa ggcatccagc acagtggcgg ccgcaatatt tgcatgtcgc 5220 tatgtgttct gggaaatcac cataaacgtg aaatccctat cagtgataga gacttataag 5280 ttccctatca gtgatagaga accggtgggc actcttccgt ggtctggtgg ataaattcgc 5340 aagggtatca tggcggacga ccggggttcg agccccgtat ccggccgtcc gccgtgatcc 5400 atgcggttac cgcccgcgtg tcgaacccag gtgtgcgacg tcagacaacg ggggagtgct 5460 cctttttgaa ttccactttg gccgcggctc gagggggttg gggttgcgcc ttttccaagg 5520 cagccctggg tttgcgcagg gacgcggctg ctctgggcgt ggttccggga aacgcagcgg 5580 cgccgaccct gggtctcgca cattcttcac gtccgttcgc agcgtcaccc ggatcttcgc 5640 cgctaccctt gtgggccccc cggcgacgct tcctgctccg cccctaagtc gggaaggttc 5700 cttgcggttc gcggcgtgcc ggacgtgaca aacggaagcc gcacgtctca ctagtaccct 5760 cgcagacgga cagcgccagg gagcaatggc agcgcgccga ccgcgatggg ctgtggccaa 5820 tagcggctgc tcagcagggc gcgccgagag cagcggccgg gaaggggcgg tgcgggaggc 5880 ggggtgtggg gcggtagtgt gggccctgtt cctgcccgcg cggtgttccg cattctgcaa 5940 gcctccggag cgcacgtcgg cagtcggctc cctcgttgac cgaatcaccg acctctctcc 6000 ccagggggat ctgtgagttt ggggaccctt gattgttctt tctttttcgc tattgtaaaa 6060 ttcatgttat atggaggggg caaagttttc agggtgttgt ttagaatggg aagatgtccc 6120 ttgtatcacc atggaccctc atgataattt tgtttctttc actttctact ctgttgacaa 6180 ccattgtctc ctcttatttt cttttcattt tctgtaactt tttcgttaaa ctttagcttg 6240 catttgtaac gaatttttaa attcactttt gtttatttgt cagattgtaa gtactttctc 6300 taatcacttt tttttcaagg caatcagggt atattatatt gtacttcagc acagttttag 6360 agaacaattg ttataattaa atgataaggt agaatatttc tgcatataaa ttctggctgg 6420 cgtggaaata ttcttattgg tagaaacaac tacatcctgg tcatcatcct gcctttctct 6480 ttatggttac aatgatatac actgtttgag atgaggataa aatactctga gtccaaaccg 6540 ggcccctctg ctaaccatgt tcatgccttc ttctttttcc tacagctcct gggcaacgtg 6600 ctggttattg tgctgtctca tcattttggc aaagaattgt aatacgactc actatagggc 6660 gagccaccat ggctagatta gataaaagta aagtgattaa cagcgcatta gagctgctta 6720 atgaggtcgg aatcgaaggt ttaacaaccc gtaaactcgc ccagaagcta ggtgtagagc 6780 agcctacatt gtattggcat gtaaaaaata agcgggcttt gctcgacgcc ttagccattg 6840 agatgttaga taggcaccat actcactttt gccctttaga aggggaaagc tggcaagatt 6900 ttttacgtaa taacgctaaa agttttagat gtgctttact aagtcatcgc gatggagcaa 6960 aagtacattt aggtacacgg cctacagaaa aacagtatga aactctcgaa aatcaattag 7020 cctttttatg ccaacaaggt ttttcactag agaatgcctt atatgcactc agcgccgtgg 7080 ggcattttac tttaggttgc gtattggaag atcaagagca tcaagtcgct aaagaagaaa 7140 gggaaacacc tactactgat agtatgccgc cattattacg acaagctatc gaattatttg 7200 atcaccaagg tgcagagcca gccttcttat tcggccttga attgatcata tgcggattag 7260 aaaaacaact taaatgtgaa agtgggtccc caaaaaagaa gagaaaggtc gacggcggtg 7320 gtgctttgtc tcctcagcac tctgctgtca ctcaaggaag tatcatcaag aacaaggagg 7380 gcatggatgc taagtcacta actgcctggt cccggacact ggtgaccttc aaggatgtat 7440 ttgtggactt caccagggag gagtggaagc tgctggacac tgctcagcag atcgtgtaca 7500 gaaatgtgat gctggagaac tataagaacc tggtttcctt gggttatcag cttactaagc 7560 cagatgtgat cctccggttg gagaagggag aagagccctg gctggtggag agagaaattc 7620 accaagagac ccatcctgat tcagagactg catttgaaat caaatcatca gtttaagcgt 7680 acagcggctc ccgggagttc tagggatctg cccctctccc tccccccccc ctaacgttac 7740 tggccgaagc cgcttggaat aaggccggtg tgcgtttgtc tatatgttat tttccaccat 7800 attgccgtct tttggcaatg tgagggcccg gaaacctggc cctgtcttct tgacgagcat 7860 tcctaggggt ctttcccctc tcgccaaagg aatgcaaggt ctgttgaatg tcgtgaagga 7920 agcagttcct ctggaagctt cttgaagaca aacaacgtct gtagcgaccc tttgcaggca 7980 gcggaacccc ccacctggcg acaggtgcct ctgcggccaa aagccacgtg tataagatac 8040 acctgcaaag gcggcacaac cccagtgcca cgttgtgagt tggatagttg tggaaagagt 8100 caaatggctc tcctcaagcg tattcaacaa ggggctgaag gatgcccaga aggtacccca 8160 ttgtatggga tctgatctgg ggcctcggtg cacatgcttt acatgtgttt agtcgaggtt 8220 aaaaaaacgt ctaggccccc cgaaccacgg ggacgtggtt ttcctttgaa aaacacgatg 8280 ataaggatcc accggaggcc accatgaccg agtacaagcc cacggtgcgc ctcgccaccc 8340 gcgacgacgt ccccagggcc gtacgcaccc tcgccgccgc gttcgccgac taccccgcca 8400 cgcgccacac cgtcgatccg gaccgccaca tcgagcgggt caccgagctg caagaactct 8460 tcctcacgcg cgtcgggctc gacatcggca aggtgtgggt cgcggacgac ggcgccgcgg 8520 tggcggtctg gaccacgccg gagagcgtcg aagcgggggc ggtgttcgcc gagatcggcc 8580 cgcgcatggc cgagttgagc ggttcccggc tggccgcgca gcaacagatg gaaggcctcc 8640 tggcgccgca ccggcccaag gagcccgcgt ggttcctggc caccgtcggc gtctcgcccg 8700 accaccaggg caagggtctg ggcagcgccg tcgtgctccc cggagtggag gcggccgagc 8760 gcgccggggt gcccgccttc ctggagacct ccgcgccccg caacctcccc ttctacgagc 8820 ggctcggctt caccgtcacc gccgacgtcg aggtgcccga aggaccgcgc acctggtgca 8880 tgacccgcaa gcccggtgcc tgaccgcgtc tggaacaatc aacctctgga ttacaaaatt 8940 tgtgaaagat tgactggtat tcttaactat gttgctcctt ttacgctatg tggatacgct 9000 gctttaatgc ctttgtatca tgctattgct tcccgtatgg ctttcatttt ctcctccttg 9060 tataaatcct ggttgctgtc tctttatgag gagttgtggc ccgttgtcag gcaacgtggc 9120 gtggtgtgca ctgtgtttgc tgacgcaacc cccactggtt ggggcattgc caccacctgt 9180 cagctccttt ccgggacttt cgctttcccc ctccctattg ccacggcgga actcatcgcc 9240 gcctgccttg cccgctgctg gacaggggct cggctgttgg gcactgacaa ttccgtggtg 9300 ttgtcgggga agctgacgtc ctttccatgg ctgctcgcct gtgttgccac ctggattctg 9360 cgcgggacgt ccttctgcta cgtcccttcg gccctcaatc cagcggacct tccttcccgc 9420 ggcctgctgc cggctctgcg gcctcttccg cgtcttcgcc ttcgccctca gacgagtcgg 9480 atctcccttt gggccgcctc cccgcaaaat gaccgaccaa gcgacgccca acctgccatc 9540 acgagatttc gattccaccg ccgccttcta tgaaaggttg ggcttcggaa tcgttttccg 9600 ggacgccggc tggatgatcc tccagcgcgg ggatctcatg ctggagttct tcgcccaccc 9660 caacttgttt attgcagctt ataatggtta caaataaagc aatagcatca caaatttcac 9720 aaataaagca tttttttcac tgcattctag ttgtggtttg tccaaactca tcaatgtatc 9780 ttatcatgtc tgtataccgt cgacctctag ctagagcttg gcgtaatcat ggtcatagct 9840 gtttcctgtg tgaaattgtt atccgctcac aattccacac aacatacgag ccggaagcat 9900 aaagtgtaaa gcctggggtg cctaatgagt gagctaactc acattaattg cgttgcgctc 9960 actgcccgct ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg 10020 cgcggggaga ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct 10080 gcgctcggtc gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt 10140 atccacagaa tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc 10200 caggaaccgt aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga 10260 gcatcacaaa aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata 10320 ccaggcgttt ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac 10380 cggatacctg tccgcctttc tcccttcggg aagcgtggcg ctttctcata gctcacgctg 10440 taggtatctc agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc 10500 cgttcagccc gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag 10560 acacgactta tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt 10620 aggcggtgct acagagttct tgaagtggtg gcctaactac ggctacacta gaagaacagt 10680 atttggtatc tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg 10740 atccggcaaa caaaccaccg ctggtagcgg tttttttgtt tgcaagcagc agattacgcg 10800 cagaaaaaaa ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg 10860 gaacgaaaac tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta 10920 gatcctttta aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg 10980 gtctgacagt taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg 11040 ttcatccata gttgcctgac tccccgtcgt gtagataact acgatacggg agggcttacc 11100 atctggcccc agtgctgcaa tgataccgcg agacccacgc tcaccggctc cagatttatc 11160 agcaataaac cagccagccg gaagggccga gcgcagaagt ggtcctgcaa ctttatccgc 11220 ctccatccag tctattaatt gttgccggga agctagagta agtagttcgc cagttaatag 11280 tttgcgcaac gttgttgcca ttgctacagg catcgtggtg tcacgctcgt cgtttggtat 11340 ggcttcattc agctccggtt cccaacgatc aaggcgagtt acatgatccc ccatgttgtg 11400 caaaaaagcg gttagctcct tcggtcctcc gatcgttgtc agaagtaagt tggccgcagt 11460 gttatcactc atggttatgg cagcactgca taattctctt actgtcatgc catccgtaag 11520 atgcttttct gtgactggtg agtactcaac caagtcattc tgagaatagt gtatgcggcg 11580 accgagttgc tcttgcccgg cgtcaatacg ggataatacc gcgccacata gcagaacttt 11640 aaaagtgctc atcattggaa aacgttcttc ggggcgaaaa ctctcaagga tcttaccgct 11700 gttgagatcc agttcgatgt aacccactcg tgcacccaac tgatcttcag catcttttac 11760 tttcaccagc gtttctgggt gagcaaaaac aggaaggcaa aatgccgcaa aaaagggaat 11820 aagggcgaca cggaaatgtt gaatactcat actcttcctt tttcaatatt attgaagcat 11880 ttatcagggt tattgtctca tgagcggata catatttgaa tgtatttaga aaaataaaca 11940 aataggggtt ccgcgcacat ttccccgaaa agtgccacct gacgtc 11986 <210> 2 <211> 11641 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 2 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgttgacatt 240 gattattgac tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata 300 tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc 360 cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc 420 attgacgtca atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt 480 atcatatgcc aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt 540 atgcccagta catgacctta tgggactttc ctacttggca gtacatctac gtattagtca 600 tcgctattac catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg 660 actcacgggg atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc 720 aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 780 gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca 840 ctgcttactg gcttatcgaa attaatacga ctcactatag ggagacccaa gctggctagc 900 gtttaaactt aagcttggta ccgagctcgg atccactagt ccagtgtggt ggaattcctg 960 cttcgcgatg tacgggccag atatacgcgt tgacattgat tattgactag ttattaatag 1020 taatcaatta cggggtcatt agttcatagc ccatatatgg agttccgcgt tacataactt 1080 acggtaaatg gcccgcctgg ctgaccgccc aacgaccccc gcccattgac gtcaataatg 1140 acgtatgttc ccatagtaac gccaataggg actttccatt gacgtcaatg ggtggagtat 1200 ttacggtaaa ctgcccactt ggcagtacat caagtgtatc atatgccaag tacgccccct 1260 attgacgtca atgacggtaa atggcccgcc tggcattatg cccagtacat gaccttatgg 1320 gactttccta cttggcagta catctacgta ttagtcatcg ctattaccat ggtgatgcgg 1380 ttttggcagt acatcaatgg gcgtggatag cggtttgact cacggggatt tccaagtctc 1440 caccccattg acgtcaatgg gagtttgttt tggaaccaaa atcaacggga ctttccaaaa 1500 tgtcgtaaca actccgcccc attgacgcaa atgggcggta ggcgtgtacg gtgggaggtc 1560 tatataagca gagctctccc tatcagtgat agagatctcc ctatcagtga tagagatcgt 1620 cgacgagctc gtttagtgaa ccgtcagatc gcctggagac gccatccacg ctgttttgac 1680 ctccatagaa gacaccggga ccgatccagc ctccggactc tagcgtttaa acttaagctt 1740 gccaccatgg ccagtcggga agaggagcag cgcgaaacca cccccgagcg cggacgcggt 1800 gcggcgcgac gtcccccaac catggaggac gtgtcgtccc cgtccccgtc gccgccgcct 1860 ccccgggcgc ccccaaaaaa gcggatgagg cggcgtatcg agtccgagga cgaggaagac 1920 tcatcacaag acgcgctggt gccgcgcaca cccagcccgc ggccatcgac ctcggcggcg 1980 gatttggcca ttgcgcccaa gaagaaaaag aagcgccctt ctcccaagcc cgagcgcccg 2040 ccatcaccag aggtaatcgt ggacagcgag gaagaaagag aagatgtggc gctacaaatg 2100 gtgggtttca gcaacccacc ggtgctaatc aagcatggca aaggaggtaa gcgcacagtg 2160 cggcggctga atgaagacga cccagtggcg cgtggtatgc ggacgcaaga ggaagaggaa 2220 gagcccagcg aagcggaaag tgaaattacg gtgatgaacc cgctgagtgt gccgatcgtg 2280 tctgcgtggg agaagggcat ggaggctgcg cgcgcgctga tggacaagta ccacgtggat 2340 aacgatctaa aggcgaactt caaactactg cctgaccaag tggaagctct ggcggccgta 2400 tgcaagacct ggctgaacga ggagcaccgc gggttgcagc tgaccttcac cagcaacaag 2460 acctttgtga cgatgatggg gcgattcctg caggcgtacc tgcagtcgtt tgcagaggtg 2520 acctacaagc atcacgagcc cacgggctgc gcgttgtggc tgcaccgctg cgctgagatc 2580 gaaggcgagc ttaagtgtct acacggaagc attatgataa ataaggagca cgtgattgaa 2640 atggatgtga cgagcgaaaa cgggcagcgc gcgctgaagg agcagtctag caaggccaag 2700 atcgtgaaga accggtgggg ccgaaatgtg gtgcagatct ccaacaccga cgcaaggtgc 2760 tgcgtgcacg acgcggcctg tccggccaat cagttttccg gcaagtcttg cggcatgttc 2820 ttctctgaag gcgcaaaggc tcaggtggct tttaagcaga tcaaggcttt tatgcaggcg 2880 ctgtatccta acgcccagac cgggcacggt caccttttga tgccactacg gtgcgagtgc 2940 aactcaaagc ctgggcacgc gccctttttg ggaaggcagc taccaaagtt gactccgttc 3000 gccctgagca acgcggagga cctggacgcg gatctgatct ccgacaagag cgtgctggcc 3060 agcgtgcacc acccggcgct gatagtgttc cagtgctgca accctgtgta tcgcaactcg 3120 cgcgcgcagg gcggaggccc caactgcgac ttcaagatat cggcgcccga cctgctaaac 3180 gcgttggtga tggtgcgcag cctgtggagt gaaaacttca ccgagctgcc gcggatggtt 3240 gtgcctgagt ttaagtggag cactaaacac cagtatcgca acgtgtccct gccagtggcg 3300 catagcgatg cgcggcagaa cccctttgat ttttaacccg ggagttctag ggatctgccc 3360 ctctccctcc ccccccccta acgttactgg ccgaagccgc ttggaataag gccggtgtgc 3420 gtttgtctat atgttatttt ccaccatatt gccgtctttt ggcaatgtga gggcccggaa 3480 acctggccct gtcttcttga cgagcattcc taggggtctt tcccctctcg ccaaaggaat 3540 gcaaggtctg ttgaatgtcg tgaaggaagc agttcctctg gaagcttctt gaagacaaac 3600 aacgtctgta gcgacccttt gcaggcagcg gaacccccca cctggcgaca ggtgcctctg 3660 cggccaaaag ccacgtgtat aagatacacc tgcaaaggcg gcacaacccc agtgccacgt 3720 tgtgagttgg atagttgtgg aaagagtcaa atggctctcc tcaagcgtat tcaacaaggg 3780 gctgaaggat gcccagaagg taccccattg tatgggatct gatctggggc ctcggtgcac 3840 atgctttaca tgtgtttagt cgaggttaaa aaaacgtcta ggccccccga accacgggga 3900 cgtggttttc ctttgaaaaa cacgatgata aggatccacc ggaggccacc atgactacgt 3960 ccggcgttcc atttggcatg acactacgac caacacgatc tcggttgtct cggcgcactc 4020 cgtacagtag ggatcgtcta cctccttttg agacagaaac ccgcgctacc atactggagg 4080 atcatccgct gctgcccgaa tgtaacactt tgacaatgca caacgtgagt tacgtgcgag 4140 gtcttccctg cagtgtggga tttacgctga ttcaggaatg ggttgttccc tgggatatgg 4200 ttctaacgcg ggaggagctt gtaatcctga ggaagtgtat gcacgtgtgc ctgtgttgtg 4260 ccaacattga tatcatgacg agcatgatga tccatggtta cgagtcctgg gctctccact 4320 gtcattgttc cagtcccggt tccctgcagt gtatagccgg cgggcaggtt ttggccagct 4380 ggtttaggat ggtggtggat ggcgccatgt ttaatcagag gtttatatgg taccgggagg 4440 tggtgaatta caacatgcca aaagaggtaa tgtttatgtc cagcgtgttt atgaggggtc 4500 gccacttaat ctacctgcgc ttgtggtatg atggccacgt gggttctgtg gtccccgcca 4560 tgagctttgg atacagcgcc ttgcactgtg ggattttgaa caatattgtg gtgctgtgct 4620 gcagttactg tgctgattta agtgagatca gggtgcgctg ctgtgcccgg aggacaaggc 4680 gccttatgct gcgggcggtg cgaatcatcg ctgaggagac cactgccatg ttgtattcct 4740 gcaggacgga gcggcggcgg cagcagttta ttcgcgcgct gctgcagcac caccgcccta 4800 tcctgatgca cgattatgac tctaccccca tgtaggcggc cgctcgagtc tagagggccc 4860 gtttaaaccc gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc 4920 ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa 4980 aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 5040 gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 5100 ggctctatgg cttctgaggc ggaaagaacc agctggggct ctagggggta tccccggggt 5160 tggggttgcg ccttttccaa ggcatccagc acagtggcgg ccgcaatatt tgcatgtcgc 5220 tatgtgttct gggaaatcac cataaacgtg aaatccctat cagtgataga gacttataag 5280 ttccctatca gtgatagaga accggtgggc actcttccgt ggtctggtgg ataaattcgc 5340 aagggtatca tggcggacga ccggggttcg agccccgtat ccggccgtcc gccgtgatcc 5400 atgcggttac cgcccgcgtg tcgaacccag gtgtgcgacg tcagacaacg ggggagtgct 5460 cctttttgaa ttccactttg gccgcggctc gagggggttg gggttgcgcc ttttccaagg 5520 cagccctggg tttgcgcagg gacgcggctg ctctgggcgt ggttccggga aacgcagcgg 5580 cgccgaccct gggtctcgca cattcttcac gtccgttcgc agcgtcaccc ggatcttcgc 5640 cgctaccctt gtgggccccc cggcgacgct tcctgctccg cccctaagtc gggaaggttc 5700 cttgcggttc gcggcgtgcc ggacgtgaca aacggaagcc gcacgtctca ctagtaccct 5760 cgcagacgga cagcgccagg gagcaatggc agcgcgccga ccgcgatggg ctgtggccaa 5820 tagcggctgc tcagcagggc gcgccgagag cagcggccgg gaaggggcgg tgcgggaggc 5880 ggggtgtggg gcggtagtgt gggccctgtt cctgcccgcg cggtgttccg cattctgcaa 5940 gcctccggag cgcacgtcgg cagtcggctc cctcgttgac cgaatcaccg acctctctcc 6000 ccagggggat ctgtgagttt ggggaccctt gattgttctt tctttttcgc tattgtaaaa 6060 ttcatgttat atggaggggg caaagttttc agggtgttgt ttagaatggg aagatgtccc 6120 ttgtatcacc atggaccctc atgataattt tgtttctttc actttctact ctgttgacaa 6180 ccattgtctc ctcttatttt cttttcattt tctgtaactt tttcgttaaa ctttagcttg 6240 catttgtaac gaatttttaa attcactttt gtttatttgt cagattgtaa gtactttctc 6300 taatcacttt tttttcaagg caatcagggt atattatatt gtacttcagc acagttttag 6360 agaacaattg ttataattaa atgataaggt agaatatttc tgcatataaa ttctggctgg 6420 cgtggaaata ttcttattgg tagaaacaac tacatcctgg tcatcatcct gcctttctct 6480 ttatggttac aatgatatac actgtttgag atgaggataa aatactctga gtccaaaccg 6540 ggcccctctg ctaaccatgt tcatgccttc ttctttttcc tacagctcct gggcaacgtg 6600 ctggttattg tgctgtctca tcattttggc aaagaattgt aatacgactc actatagggc 6660 gagccaccat ggctagatta gataaaagta aagtgattaa cagcgcatta gagctgctta 6720 atgaggtcgg aatcgaaggt ttaacaaccc gtaaactcgc ccagaagcta ggtgtagagc 6780 agcctacatt gtattggcat gtaaaaaata agcgggcttt gctcgacgcc ttagccattg 6840 agatgttaga taggcaccat actcactttt gccctttaga aggggaaagc tggcaagatt 6900 ttttacgtaa taacgctaaa agttttagat gtgctttact aagtcatcgc gatggagcaa 6960 aagtacattt aggtacacgg cctacagaaa aacagtatga aactctcgaa aatcaattag 7020 cctttttatg ccaacaaggt ttttcactag agaatgcctt atatgcactc agcgccgtgg 7080 ggcattttac tttaggttgc gtattggaag atcaagagca tcaagtcgct aaagaagaaa 7140 gggaaacacc tactactgat agtatgccgc cattattacg acaagctatc gaattatttg 7200 atcaccaagg tgcagagcca gccttcttat tcggccttga attgatcata tgcggattag 7260 aaaaacaact taaatgtgaa agtgggtccc caaaaaagaa gagaaaggtc gacggcggtg 7320 gttcagttta agcgtacagc ggctcccggg agttctaggg atctgcccct ctccctcccc 7380 cccccctaac gttactggcc gaagccgctt ggaataaggc cggtgtgcgt ttgtctatat 7440 gttattttcc accatattgc cgtcttttgg caatgtgagg gcccggaaac ctggccctgt 7500 cttcttgacg agcattccta ggggtctttc ccctctcgcc aaaggaatgc aaggtctgtt 7560 gaatgtcgtg aaggaagcag ttcctctgga agcttcttga agacaaacaa cgtctgtagc 7620 gaccctttgc aggcagcgga accccccacc tggcgacagg tgcctctgcg gccaaaagcc 7680 acgtgtataa gatacacctg caaaggcggc acaaccccag tgccacgttg tgagttggat 7740 agttgtggaa agagtcaaat ggctctcctc aagcgtattc aacaaggggc tgaaggatgc 7800 ccagaaggta ccccattgta tgggatctga tctggggcct cggtgcacat gctttacatg 7860 tgtttagtcg aggttaaaaa aacgtctagg ccccccgaac cacggggacg tggttttcct 7920 ttgaaaaaca cgatgataag gatccaccgg aggccaccat gaccgagtac aagcccacgg 7980 tgcgcctcgc cacccgcgac gacgtcccca gggccgtacg caccctcgcc gccgcgttcg 8040 ccgactaccc cgccacgcgc cacaccgtcg atccggaccg ccacatcgag cgggtcaccg 8100 agctgcaaga actcttcctc acgcgcgtcg ggctcgacat cggcaaggtg tgggtcgcgg 8160 acgacggcgc cgcggtggcg gtctggacca cgccggagag cgtcgaagcg ggggcggtgt 8220 tcgccgagat cggcccgcgc atggccgagt tgagcggttc ccggctggcc gcgcagcaac 8280 agatggaagg cctcctggcg ccgcaccggc ccaaggagcc cgcgtggttc ctggccaccg 8340 tcggcgtctc gcccgaccac cagggcaagg gtctgggcag cgccgtcgtg ctccccggag 8400 tggaggcggc cgagcgcgcc ggggtgcccg ccttcctgga gacctccgcg ccccgcaacc 8460 tccccttcta cgagcggctc ggcttcaccg tcaccgccga cgtcgaggtg cccgaaggac 8520 cgcgcacctg gtgcatgacc cgcaagcccg gtgcctgacc gcgtctggaa caatcaacct 8580 ctggattaca aaatttgtga aagattgact ggtattctta actatgttgc tccttttacg 8640 ctatgtggat acgctgcttt aatgcctttg tatcatgcta ttgcttcccg tatggctttc 8700 attttctcct ccttgtataa atcctggttg ctgtctcttt atgaggagtt gtggcccgtt 8760 gtcaggcaac gtggcgtggt gtgcactgtg tttgctgacg caacccccac tggttggggc 8820 attgccacca cctgtcagct cctttccggg actttcgctt tccccctccc tattgccacg 8880 gcggaactca tcgccgcctg ccttgcccgc tgctggacag gggctcggct gttgggcact 8940 gacaattccg tggtgttgtc ggggaagctg acgtcctttc catggctgct cgcctgtgtt 9000 gccacctgga ttctgcgcgg gacgtccttc tgctacgtcc cttcggccct caatccagcg 9060 gaccttcctt cccgcggcct gctgccggct ctgcggcctc ttccgcgtct tcgccttcgc 9120 cctcagacga gtcggatctc cctttgggcc gcctccccgc aaaatgaccg accaagcgac 9180 gcccaacctg ccatcacgag atttcgattc caccgccgcc ttctatgaaa ggttgggctt 9240 cggaatcgtt ttccgggacg ccggctggat gatcctccag cgcggggatc tcatgctgga 9300 gttcttcgcc caccccaact tgtttattgc agcttataat ggttacaaat aaagcaatag 9360 catcacaaat ttcacaaata aagcattttt ttcactgcat tctagttgtg gtttgtccaa 9420 actcatcaat gtatcttatc atgtctgtat accgtcgacc tctagctaga gcttggcgta 9480 atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc cacacaacat 9540 acgagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgagct aactcacatt 9600 aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta 9660 atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt ccgcttcctc 9720 gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa 9780 ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa 9840 aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt tccataggct 9900 ccgcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc gaaacccgac 9960 aggactataa agataccagg cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc 10020 gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg tggcgctttc 10080 tcatagctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca agctgggctg 10140 tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact atcgtcttga 10200 gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta acaggattag 10260 cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta actacggcta 10320 cactagaaga acagtatttg gtatctgcgc tctgctgaag ccagttacct tcggaaaaag 10380 agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggttttt ttgtttgcaa 10440 gcagcagatt acgcgcagaa aaaaaggatc tcaagaagat cctttgatct tttctacggg 10500 gtctgacgct cagtggaacg aaaactcacg ttaagggatt ttggtcatga gattatcaaa 10560 aaggatcttc acctagatcc ttttaaatta aaaatgaagt tttaaatcaa tctaaagtat 10620 atatgagtaa acttggtctg acagttacca atgcttaatc agtgaggcac ctatctcagc 10680 gatctgtcta tttcgttcat ccatagttgc ctgactcccc gtcgtgtaga taactacgat 10740 acgggagggc ttaccatctg gccccagtgc tgcaatgata ccgcgagacc cacgctcacc 10800 ggctccagat ttatcagcaa taaaccagcc agccggaagg gccgagcgca gaagtggtcc 10860 tgcaacttta tccgcctcca tccagtctat taattgttgc cgggaagcta gagtaagtag 10920 ttcgccagtt aatagtttgc gcaacgttgt tgccattgct acaggcatcg tggtgtcacg 10980 ctcgtcgttt ggtatggctt cattcagctc cggttcccaa cgatcaaggc gagttacatg 11040 atcccccatg ttgtgcaaaa aagcggttag ctccttcggt cctccgatcg ttgtcagaag 11100 taagttggcc gcagtgttat cactcatggt tatggcagca ctgcataatt ctcttactgt 11160 catgccatcc gtaagatgct tttctgtgac tggtgagtac tcaaccaagt cattctgaga 11220 atagtgtatg cggcgaccga gttgctcttg cccggcgtca atacgggata ataccgcgcc 11280 acatagcaga actttaaaag tgctcatcat tggaaaacgt tcttcggggc gaaaactctc 11340 aaggatctta ccgctgttga gatccagttc gatgtaaccc actcgtgcac ccaactgatc 11400 ttcagcatct tttactttca ccagcgtttc tgggtgagca aaaacaggaa ggcaaaatgc 11460 cgcaaaaaag ggaataaggg cgacacggaa atgttgaata ctcatactct tcctttttca 11520 atattattga agcatttatc agggttattg tctcatgagc ggatacatat ttgaatgtat 11580 ttagaaaaat aaacaaatag gggttccgcg cacatttccc cgaaaagtgc cacctgacgt 11640 c 11641 <210> 3 <211> 110 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 3 tatttaatct ccctatcagt gatagagatc tccctatcag tgatagagat cgcccgagtg 60 agcacgcagg gtctccattt tgaagcggga ggtttgaacg cgcagccgcc 110 <210> 4 <211> 108 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 4 tatttaatct ccctatcagt gatagagatc gcccgagtga gcacgcaggg tctccatttt 60 gatccctatc agtgatagag aagcgggagg tttgaacgcg cagccgcc 108 <210> 5 <211> 106 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 5 tccctatcag tgatagagat ctatttaagc ccgagtgagc acgcagtccc tatcagtgat 60 agagaggtct ccattttgaa gcgggaggtt tgaacgcgca gccgcc 106 <210> 6 <211> 183 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 6 ccagaaatgg cgccggaggc gggaacaagg tggtggatga gtgctacatc cccaattact 60 tgctccccaa aacccagcct gagctccagt gggcgtggac taatatggaa cagtatttaa 120 gcgcctgtcc ctatcagtga tagagatctc cctatcagtg atagagattt gaatctcacg 180 gag 183 <210> 7 <211> 181 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 7 ccagaaatgg cgccggaggc gggaacaagg tggtggatga gtgctacatc cccaattact 60 tgctccccaa aacccagcct gagtccctat cagtgataga gactccagtg ggcgtggact 120 aatatggaac agtatttaag cgcctgtccc tatcagtgat agagatttga atctcacgga 180 g 181 <210> 8 <211> 181 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 8 ccagaaatgg cgccggaggc gggaacaagg tggtggatga gtgctacatc cccaattact 60 tgctccccaa aacccagcct gagctccagt gggcgtggac taatatggaa tccctatcag 120 tgatagagac agtatttaag cgcctgtccc tatcagtgat agagatttga atctcacgga 180 g 181 <210> 9 <211> 221 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 9 ccagaaatgg cgccggaggc gggaacaagg tggtggatga gtgctacatc cccaattact 60 tgctccccaa aacccagcct gagctccagt gggcgtggac taatatggaa cagtatttaa 120 ggtaagttcc ctatcagtga tagagatctc cctatcagtg atagagatac tgacatccac 180 tttgcctttc tctccacagc gcctgtttga atctcacgga g 221 <210> 10 <211> 223 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 10 ccagaaatgg cgccggaggc gggaacaagg tggtggatga gtgctacatc cccaattact 60 tgctccccaa aacccagcct gagctccagt gggcgtggac taatatggaa cagtatttaa 120 gcgcctgttt gaatctcacg gaaaggtaag ttccctatca gtgatagaga tctccctatc 180 agtgatagag atactgacat ccactttgcc tttctctcca cag 223 <210> 11 <211> 18281 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 11 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcgtttaaac ttaagcttgg taccgagctc ggatccacta 1560 gtccagtgtg gtggaattcc tgcttcgcga tgtacgggcc agatatacgc gttgacattg 1620 attattgact agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat 1680 ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc 1740 ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca 1800 ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta 1860 tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 1920 tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 1980 cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 2040 ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggaacca 2100 aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 2160 taggcgtgta cggtgggagg tctatataag cagagctctc cctatcagtg atagagatct 2220 ccctatcagt gatagagatc gtcgacgagc tcgtttagtg aaccgtcaga tcgcctggag 2280 acgccatcca cgctgttttg acctccatag aagacaccgg gaccgatcca gcctccggac 2340 tctagcgttt aaacttaagc ttgccaccat ggccagtcgg gaagaggagc agcgcgaaac 2400 cacccccgag cgcggacgcg gtgcggcgcg acgtccccca accatggagg acgtgtcgtc 2460 cccgtccccg tcgccgccgc ctccccgggc gcccccaaaa aagcggatga ggcggcgtat 2520 cgagtccgag gacgaggaag actcatcaca agacgcgctg gtgccgcgca cacccagccc 2580 gcggccatcg acctcggcgg cggatttggc cattgcgccc aagaagaaaa agaagcgccc 2640 ttctcccaag cccgagcgcc cgccatcacc agaggtaatc gtggacagcg aggaagaaag 2700 agaagatgtg gcgctacaaa tggtgggttt cagcaaccca ccggtgctaa tcaagcatgg 2760 caaaggaggt aagcgcacag tgcggcggct gaatgaagac gacccagtgg cgcgtggtat 2820 gcggacgcaa gaggaagagg aagagcccag cgaagcggaa agtgaaatta cggtgatgaa 2880 cccgctgagt gtgccgatcg tgtctgcgtg ggagaagggc atggaggctg cgcgcgcgct 2940 gatggacaag taccacgtgg ataacgatct aaaggcgaac ttcaaactac tgcctgacca 3000 agtggaagct ctggcggccg tatgcaagac ctggctgaac gaggagcacc gcgggttgca 3060 gctgaccttc accagcaaca agacctttgt gacgatgatg gggcgattcc tgcaggcgta 3120 cctgcagtcg tttgcagagg tgacctacaa gcatcacgag cccacgggct gcgcgttgtg 3180 gctgcaccgc tgcgctgaga tcgaaggcga gcttaagtgt ctacacggaa gcattatgat 3240 aaataaggag cacgtgattg aaatggatgt gacgagcgaa aacgggcagc gcgcgctgaa 3300 ggagcagtct agcaaggcca agatcgtgaa gaaccggtgg ggccgaaatg tggtgcagat 3360 ctccaacacc gacgcaaggt gctgcgtgca cgacgcggcc tgtccggcca atcagttttc 3420 cggcaagtct tgcggcatgt tcttctctga aggcgcaaag gctcaggtgg cttttaagca 3480 gatcaaggct tttatgcagg cgctgtatcc taacgcccag accgggcacg gtcacctttt 3540 gatgccacta cggtgcgagt gcaactcaaa gcctgggcac gcgccctttt tgggaaggca 3600 gctaccaaag ttgactccgt tcgccctgag caacgcggag gacctggacg cggatctgat 3660 ctccgacaag agcgtgctgg ccagcgtgca ccacccggcg ctgatagtgt tccagtgctg 3720 caaccctgtg tatcgcaact cgcgcgcgca gggcggaggc cccaactgcg acttcaagat 3780 atcggcgccc gacctgctaa acgcgttggt gatggtgcgc agcctgtgga gtgaaaactt 3840 caccgagctg ccgcggatgg ttgtgcctga gtttaagtgg agcactaaac accagtatcg 3900 caacgtgtcc ctgccagtgg cgcatagcga tgcgcggcag aacccctttg atttttaacc 3960 cgggagttct agggatctgc ccctctccct cccccccccc taacgttact ggccgaagcc 4020 gcttggaata aggccggtgt gcgtttgtct atatgttatt ttccaccata ttgccgtctt 4080 ttggcaatgt gagggcccgg aaacctggcc ctgtcttctt gacgagcatt cctaggggtc 4140 tttcccctct cgccaaagga atgcaaggtc tgttgaatgt cgtgaaggaa gcagttcctc 4200 tggaagcttc ttgaagacaa acaacgtctg tagcgaccct ttgcaggcag cggaaccccc 4260 cacctggcga caggtgcctc tgcggccaaa agccacgtgt ataagataca cctgcaaagg 4320 cggcacaacc ccagtgccac gttgtgagtt ggatagttgt ggaaagagtc aaatggctct 4380 cctcaagcgt attcaacaag gggctgaagg atgcccagaa ggtaccccat tgtatgggat 4440 ctgatctggg gcctcggtgc acatgcttta catgtgttta gtcgaggtta aaaaaacgtc 4500 taggcccccc gaaccacggg gacgtggttt tcctttgaaa aacacgatga taaggatcca 4560 ccggaggcca ccatgactac gtccggcgtt ccatttggca tgacactacg accaacacga 4620 tctcggttgt ctcggcgcac tccgtacagt agggatcgtc tacctccttt tgagacagaa 4680 acccgcgcta ccatactgga ggatcatccg ctgctgcccg aatgtaacac tttgacaatg 4740 cacaacgtga gttacgtgcg aggtcttccc tgcagtgtgg gatttacgct gattcaggaa 4800 tgggttgttc cctgggatat ggttctaacg cgggaggagc ttgtaatcct gaggaagtgt 4860 atgcacgtgt gcctgtgttg tgccaacatt gatatcatga cgagcatgat gatccatggt 4920 tacgagtcct gggctctcca ctgtcattgt tccagtcccg gttccctgca gtgtatagcc 4980 ggcgggcagg ttttggccag ctggtttagg atggtggtgg atggcgccat gtttaatcag 5040 aggtttatat ggtaccggga ggtggtgaat tacaacatgc caaaagaggt aatgtttatg 5100 tccagcgtgt ttatgagggg tcgccactta atctacctgc gcttgtggta tgatggccac 5160 gtgggttctg tggtccccgc catgagcttt ggatacagcg ccttgcactg tgggattttg 5220 aacaatattg tggtgctgtg ctgcagttac tgtgctgatt taagtgagat cagggtgcgc 5280 tgctgtgccc ggaggacaag gcgccttatg ctgcgggcgg tgcgaatcat cgctgaggag 5340 accactgcca tgttgtattc ctgcaggacg gagcggcggc ggcagcagtt tattcgcgcg 5400 ctgctgcagc accaccgccc tatcctgatg cacgattatg actctacccc catgtaggcg 5460 gccgctcgag tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag 5520 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 5580 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 5640 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 5700 caggcatgct ggggatgcgg tgggctctat ggcttctgag gcggaaagaa ccagctgggg 5760 ctctaggggg tatccccggg gttggggttg cgccttttcc aaggcatcca gcacagtggc 5820 ggccgcaata tttgcatgtc gctatgtgtt ctgggaaatc accataaacg tgaaatccct 5880 atcagtgata gagacttata agttccctat cagtgataga gaaccggtgg gcactcttcc 5940 gtggtctggt ggataaattc gcaagggtat catggcggac gaccggggtt cgagccccgt 6000 atccggccgt ccgccgtgat ccatgcggtt accgcccgcg tgtcgaaccc aggtgtgcga 6060 cgtcagacaa cgggggagtg ctcctttttg aattccactt tggccgcggc tcgagggggt 6120 tggggttgcg ccttttccaa ggcagccctg ggtttgcgca gggacgcggc tgctctgggc 6180 gtggttccgg gaaacgcagc ggcgccgacc ctgggtctcg cacattcttc acgtccgttc 6240 gcagcgtcac ccggatcttc gccgctaccc ttgtgggccc cccggcgacg cttcctgctc 6300 cgcccctaag tcgggaaggt tccttgcggt tcgcggcgtg ccggacgtga caaacggaag 6360 ccgcacgtct cactagtacc ctcgcagacg gacagcgcca gggagcaatg gcagcgcgcc 6420 gaccgcgatg ggctgtggcc aatagcggct gctcagcagg gcgcgccgag agcagcggcc 6480 gggaaggggc ggtgcgggag gcggggtgtg gggcggtagt gtgggccctg ttcctgcccg 6540 cgcggtgttc cgcattctgc aagcctccgg agcgcacgtc ggcagtcggc tccctcgttg 6600 accgaatcac cgacctctct ccccaggggg atctgtgagt ttggggaccc ttgattgttc 6660 tttctttttc gctattgtaa aattcatgtt atatggaggg ggcaaagttt tcagggtgtt 6720 gtttagaatg ggaagatgtc ccttgtatca ccatggaccc tcatgataat tttgtttctt 6780 tcactttcta ctctgttgac aaccattgtc tcctcttatt ttcttttcat tttctgtaac 6840 tttttcgtta aactttagct tgcatttgta acgaattttt aaattcactt ttgtttattt 6900 gtcagattgt aagtactttc tctaatcact tttttttcaa ggcaatcagg gtatattata 6960 ttgtacttca gcacagtttt agagaacaat tgttataatt aaatgataag gtagaatatt 7020 tctgcatata aattctggct ggcgtggaaa tattcttatt ggtagaaaca actacatcct 7080 ggtcatcatc ctgcctttct ctttatggtt acaatgatat acactgtttg agatgaggat 7140 aaaatactct gagtccaaac cgggcccctc tgctaaccat gttcatgcct tcttcttttt 7200 cctacagctc ctgggcaacg tgctggttat tgtgctgtct catcattttg gcaaagaatt 7260 gtaatacgac tcactatagg gcgagccacc atggctagat tagataaaag taaagtgatt 7320 aacagcgcat tagagctgct taatgaggtc ggaatcgaag gtttaacaac ccgtaaactc 7380 gcccagaagc taggtgtaga gcagcctaca ttgtattggc atgtaaaaaa taagcgggct 7440 ttgctcgacg ccttagccat tgagatgtta gataggcacc atactcactt ttgcccttta 7500 gaaggggaaa gctggcaaga ttttttacgt aataacgcta aaagttttag atgtgcttta 7560 ctaagtcatc gcgatggagc aaaagtacat ttaggtacac ggcctacaga aaaacagtat 7620 gaaactctcg aaaatcaatt agccttttta tgccaacaag gtttttcact agagaatgcc 7680 ttatatgcac tcagcgccgt ggggcatttt actttaggtt gcgtattgga agatcaagag 7740 catcaagtcg ctaaagaaga aagggaaaca cctactactg atagtatgcc gccattatta 7800 cgacaagcta tcgaattatt tgatcaccaa ggtgcagagc cagccttctt attcggcctt 7860 gaattgatca tatgcggatt agaaaaacaa cttaaatgtg aaagtgggtc cccaaaaaag 7920 aagagaaagg tcgacggcgg tggtgctttg tctcctcagc actctgctgt cactcaagga 7980 agtatcatca agaacaagga gggcatggat gctaagtcac taactgcctg gtcccggaca 8040 ctggtgacct tcaaggatgt atttgtggac ttcaccaggg aggagtggaa gctgctggac 8100 actgctcagc agatcgtgta cagaaatgtg atgctggaga actataagaa cctggtttcc 8160 ttgggttatc agcttactaa gccagatgtg atcctccggt tggagaaggg agaagagccc 8220 tggctggtgg agagagaaat tcaccaagag acccatcctg attcagagac tgcatttgaa 8280 atcaaatcat cagtttaagc gtacagcggc tcccgggagt tctagggatc tgcccctctc 8340 cctccccccc ccctaacgtt actggccgaa gccgcttgga ataaggccgg tgtgcgtttg 8400 tctatatgtt attttccacc atattgccgt cttttggcaa tgtgagggcc cggaaacctg 8460 gccctgtctt cttgacgagc attcctaggg gtctttcccc tctcgccaaa ggaatgcaag 8520 gtctgttgaa tgtcgtgaag gaagcagttc ctctggaagc ttcttgaaga caaacaacgt 8580 ctgtagcgac cctttgcagg cagcggaacc ccccacctgg cgacaggtgc ctctgcggcc 8640 aaaagccacg tgtataagat acacctgcaa aggcggcaca accccagtgc cacgttgtga 8700 gttggatagt tgtggaaaga gtcaaatggc tctcctcaag cgtattcaac aaggggctga 8760 aggatgccca gaaggtaccc cattgtatgg gatctgatct ggggcctcgg tgcacatgct 8820 ttacatgtgt ttagtcgagg ttaaaaaaac gtctaggccc cccgaaccac ggggacgtgg 8880 ttttcctttg aaaaacacga tgataaggat ccaccggagg ccaccatgac cgagtacaag 8940 cccacggtgc gcctcgccac ccgcgacgac gtccccaggg ccgtacgcac cctcgccgcc 9000 gcgttcgccg actaccccgc cacgcgccac accgtcgatc cggaccgcca catcgagcgg 9060 gtcaccgagc tgcaagaact cttcctcacg cgcgtcgggc tcgacatcgg caaggtgtgg 9120 gtcgcggacg acggcgccgc ggtggcggtc tggaccacgc cggagagcgt cgaagcgggg 9180 gcggtgttcg ccgagatcgg cccgcgcatg gccgagttga gcggttcccg gctggccgcg 9240 cagcaacaga tggaaggcct cctggcgccg caccggccca aggagcccgc gtggttcctg 9300 gccaccgtcg gcgtctcgcc cgaccaccag ggcaagggtc tgggcagcgc cgtcgtgctc 9360 cccggagtgg aggcggccga gcgcgccggg gtgcccgcct tcctggagac ctccgcgccc 9420 cgcaacctcc ccttctacga gcggctcggc ttcaccgtca ccgccgacgt cgaggtgccc 9480 gaaggaccgc gcacctggtg catgacccgc aagcccggtg cctgaccgcg tctggaacaa 9540 tcaacctctg gattacaaaa tttgtgaaag attgactggt attcttaact atgttgctcc 9600 ttttacgcta tgtggatacg ctgctttaat gcctttgtat catgctattg cttcccgtat 9660 ggctttcatt ttctcctcct tgtataaatc ctggttgctg tctctttatg aggagttgtg 9720 gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt gctgacgcaa cccccactgg 9780 ttggggcatt gccaccacct gtcagctcct ttccgggact ttcgctttcc ccctccctat 9840 tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc tggacagggg ctcggctgtt 9900 gggcactgac aattccgtgg tgttgtcggg gaagctgacg tcctttccat ggctgctcgc 9960 ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt cggccctcaa 10020 tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc cgcgtcttcg 10080 ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgcaaa atgaccgacc 10140 aagcgacgcc caacctgcca tcacgagatt tcgattccac cgccgccttc tatgaaaggt 10200 tgggcttcgg aatcgttttc cgggacgccg gctggatgat cctccagcgc ggggatctca 10260 tgctggagtt cttcgcccac cccaacttgt ttattgcagc ttataatggt tacaaataaa 10320 gcaatagcat cacaaatttc acaaataaag catttttttc actgcattct agttgtggtt 10380 tgtccaaact catcaatgta tcttatcatg tctgtagctg atcaattggc gcgccgaatt 10440 cgttatctgc agaattcggc ttggcggctg cgcgttcaaa cctcccgctt caaaatggag 10500 accctgcgtg ctcactcggg cttaaatacc cagcgtgacc acatggtgtc gcaaaatgtc 10560 gcaaaacact cacgtgacct ctaatacagg acctctagag catggaaact agataagaaa 10620 gaaatacgca gagaccaaag ttcaactgaa acgaattaaa cggtttattg attaacaagc 10680 aaactagttt acagattacg ggtgaggtaa cgggtgccga tggggcgagg ctcagaataa 10740 acgccatttg tgtcaacagc aaagtccaca tttgtagatt tgttgtagtt ggaagtgtat 10800 tgaatctctg ggttccagcg tttgctgttt tctttctgca gctcccattc aatttccacg 10860 ctgacctgtc cggtgctgta ctgcgtgatg aacgacgcaa acttagctgg actgaaggta 10920 gttggaggat tcgcgggaac aggtgtattc ttaatcagga tctgaggagg cgggtgtttc 10980 agtccaaagc ctcccatcag cggcgaggga tgaaagtgtc cgtccgtgtg aggaatcttg 11040 gcccagatag gaccctgcag gtacacgtcc cggtcctgcc agaccatgcc aggtaaggct 11100 ccttgactgt tgacggtccc tgtagcagga gcggtgttgg ccgattgcag gttagtggcc 11160 accgtgccgt actcttctgt ggccactggg ttggtggttt taatttcttc ctcgttggtt 11220 atcataacgt tgtcaaggtc cacgttgcta tttccagctc cctgtttccc aaatattaag 11280 actccgctca tcggaaaaaa tttgtcttcg tcgtccttgt gggttgccat agcgggaccg 11340 ggatttacca gagagtctct gccattcaga tgatacttgg tggcaccggt ccaggcaaag 11400 ttgctgttgt tattttgatt ggttgtcttg gagacgcgtt gctgccggta gcagggcccg 11460 ggtagccagt ttttggcctg attcgccatg ctactaggcc cggcctgaga aaattgcaac 11520 gtccgatttc ctgcggtacc actcgtggtc tgagtccgag acaggtagta caggtactgg 11580 tcgatgaggg ggttcatcag ccggtccagg ctttggctgt gcgcgtagct gctgtgaaaa 11640 ggcacgtcct caaacgtgta gctgaactga aagttgttgc ccgttctcag catttgagaa 11700 ggaaagtatt ccaggcagta gaaggaggaa cggcccacgg cctgactgcc attgttcaga 11760 gtcaggtacc cgtactgagg aatcatgaag acgtccgccg ggaacggagg caggcagccc 11820 tggtgcgcag agccgaggac gtacgggagc tggtattccg agtccgtaaa gacctgaacc 11880 gtgctggtaa ggttattggc gatggtcgtg gtgccatcat tcgtcgtgac ctccttgacc 11940 tggatgttga agagcttgaa gttgagcttc ttgggccgga atccccagtt gttgttgatg 12000 agtcgctgcc agtcacgtgg tgagaagtgg cagtggaatc tgttaaagtc aaaatacccc 12060 cagggggtgc tgtagccgaa gtaggtgttg tcgttggtgc tgcctcccga ttggctggag 12120 atttgcttgt agaggtggtt gttgtaggtg gggagggccc aggttcgggt gctggtggtg 12180 atgactctgt cgcccagcca tgtggaatcg caatgccaat ttcctgaggc gttacccact 12240 ccgtcggcgc cttcgttatt gtctgccatt ggagcgccac cgcctgcagc cattgtatta 12300 gatcccacac cagagggggc tgcggggggt tctccgagtg gttgagggtc gggcactgac 12360 tctgagtcgc cagtctgccc aaagttgagt ctctttctcg cgggctgctg gcctttcttg 12420 ccgatgcccg aagaggagtc tggttcctgg ggtgattgct ctaccggtct cttctttcca 12480 ggagccgtct tagcgccttc ctcaaccaga ccgagaggtt cgagaacccg cttcttggcc 12540 tggaagactg ctcgcccgag gttgccccca aaagacgtat cttcttgcag acgctcctga 12600 aactcggcgt cggcgtggtt ataccgcagg tacggattgt cacccgcttt gagctgctgg 12660 tcgtaggcct tgtcgtgctc gagggccgct gcgtccgccg cgttgacggg ctcccccttg 12720 tcgagtccgt tgaagggtcc gaggtacttg tagccaggaa gcaccagacc ccggccgtcg 12780 tcctgctttt gctggttggc tttgggtttc ggggctccag gtttcaagtc ccaccactcg 12840 cgaatgccct cagagaggtt gtcctcgagc caatctggaa gataaccatc ggcagccata 12900 cctgatttaa atcatttatt gttcaaagat gcagtcatcc aaatccacat tgaccagatc 12960 gcaggcagtg caagcgtctg gcacctttcc catgatatga tgaatgtagc acagtttctg 13020 atacgccttt ttgacgacag aaacgggttg agattctgac acgggaaagc actctaaaca 13080 gtctttctgt ccgtgagtga agcagatatt tgaattctga ttcattctct cgcattgtct 13140 gcagggaaac agcatcagat tcatgcccac gtgacgagaa catttgtttt ggtacctgtc 13200 tgcgtagttg atcgaagctt ccgcgtctga cgtcgatggc tgcgcaactg actcgcgcac 13260 ccgtttgggc tcacttatat ctgcgtcact gggggcgggt cttttcttgg ctccaccctt 13320 tttgacgtag aattcatgct ccacctcaac cacgtgatcc tttgcccacc ggaaaaagtc 13380 tttgacttcc tgcttggtga ccttcccaaa gtcatgatcc agacggcggg tgagttcaaa 13440 tttgaacatc cggtcttgca acggctgctg gtgttcgaag gtcgttgagt tcccgtcaat 13500 cacggcgcac atgttggtgt tggaggtgac gatcacggga gtcgggtcta tctgggccga 13560 ggacttgcat ttctggtcca cgcgcacctt gcttcctccg agaatggctt tggccgactc 13620 cacgaccttg gcggtcatct tcccctcctc ccaccagatc accatcttgt cgacacagtc 13680 gttgaaggga aagttctcat tggtccagtt tacgcacccg tagaagggca cagtgtgggc 13740 tatggcctcc gcgatgttgg tcttcccggt agttgcaggc ccaaacagcc agatggtgtt 13800 cctcttgccg aactttttcg tggcccatcc cagaaagacg gaagccgcat attggggatc 13860 gtacccgttt agttccaaaa ttttataaat ccgattgctg gaaatgtcct ccacgggctg 13920 ctggcccacc aggtagtcgg gggcggtttt agtcaggctc ataatctttc ccgcattgtc 13980 caaggcagcc ttgatttggg accgcgagtt ggaggccgca ttgaaggaga tgtatgaggc 14040 ctggtcctcc tggatccact gcttctccga ggtaatcccc ttgtccacga gccacccgac 14100 cagctccatg tacctggctg aagtttttga tctgatcacc ggcgcatcag aattgggatt 14160 ctgattctct ttgttctgct cctgcgtctg cgacacgtgc gtcagatgct gcgccaccaa 14220 ccgtttacgc tccgtgagat tcaaacaggc gctgtggaga gaaaggcaaa gtggatgtca 14280 gtatctctat cactgatagg gagatctcta tcactgatag ggaacttacc ttaaatactg 14340 ttccatatta gtccacgccc actggagctc aggctgggtt ttggggagca agtaattggg 14400 gatgtagcac tcatccacca ccttgttccc gcctccggcg ccatttctgg tctttgtgac 14460 cgcgaaccag tttggcaaag tcggctcgat cccgcggtaa attctctgaa tcagtttttc 14520 gcgaatctga ctcaggaaac gtcccaaaac catggatttc accccggtgg tttccacgag 14580 cacgtgcatg tggaagtagc tctctccctt ctcaaattgc acaaagaaaa gagcctccgg 14640 ggccttactc acacggcgcc attccgtcag aaagtcgcgc tgcagcttct cggccacggt 14700 caggggtgcc tgctcaatca gattcagatc catgtcagaa tctggcggca actcccattc 14760 cttctcggcc acccagttca caaagctgtc agaaatgccg ggcagatgct cgtcaaggtc 14820 gctggggacc ttaatcacaa tctcgtaaaa ccccggcatg gcggctgcgc gttcaaacct 14880 cccgcttcaa aatggagacc ctgcgtgctc actcgggcga tctctatcac tgatagggag 14940 atctctatca ctgataggga gattaaatag aatggctagg atccggccgg cctgcaggtg 15000 tcctcacagg aacgaagtcc ctaaagaaac agtggcagcc aggtttagcc ccggaattga 15060 ctggattcct tttttagggc ccattggtat ggctttttcc ccgtatcccc ccaggtgtct 15120 gcaggctcaa agagcagcga gaagcgttca gaggaaagcg atcccgtgcc accttccccg 15180 tgcccgggct gtccccgcac gctgccggct cggggatgcg gggggagcgc cggaccggag 15240 cggagccccg ggcggctcgc tgctgccccc tagcggggga gggacgtaat tacatccctg 15300 ggggctttgg gggggggctg tccctctaga gcggccgcca ccgcggtgga gctccagctt 15360 ttgttccctt tagtgagggt taattagatc ttaatacgac tcactatagg gcgaattggg 15420 taccgggccc cccctcgagg tcgacggtat cgataagctt gatatctata acaagaaaat 15480 atatatataa taagttatca cgtaagtaga acatgaaata acaatataat tatcgtatga 15540 gttaaatctt aaaagtcacg taaaagataa tcatgcgtca ttttgactca cgcggtcgtt 15600 atagttcaaa atcagtgaca cttaccgcat tgacaagcac gcctcacggg agctccaagc 15660 ggcgactgag atgtcctaaa tgcacagcga cggattcgcg ctatttagaa agagagagca 15720 atatttcaag aatgcatgcg tcaattttac gcagactatc tttctagggt taatctagct 15780 gcatcaggat catatcgtcg ggtctttttt ccggctcagt catcgcccaa gctggcgcta 15840 tctgggcatc ggggaggaag aagcccgtgc cttttcccgc gaggttgaag cggcatggaa 15900 agagtttgcc gaggatgact gctgctgcat tgacgttgag cgaaaacgca cgtttaccat 15960 gatgattcgg gaaggtgtgg ccatgcacgc ctttaacggt gaactgttcg ttcaggccac 16020 ctgggatacc agttcgtcgc ggcttttccg gacacagttc cggatggtca gcccgaagcg 16080 catcagcaac ccgaacaata ccggcgacag ccggaactgc cgtgccggtg tgcagattaa 16140 tgacagcggt gcggcgctgg gatattacgt cagcgaggac gggtatcctg gctggatgcc 16200 gcagaaatgg acatggatac cccgtgagtt acccggcggg cgcgcttggc gtaatcatgg 16260 tcatagctgt ttcctgtgtg aaattgttat ccgctcacaa ttccacacaa catacgagcc 16320 ggaagcataa agtgtaaagc ctggggtgcc taatgagtga gctaactcac attaattgcg 16380 ttgcgctcac tgcccgcttt ccagtcggga aacctgtcgt gccagctgca ttaatgaatc 16440 ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc ctcgctcact 16500 gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc aaaggcggta 16560 atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc aaaaggccag 16620 caaaaggcca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag gctccgcccc 16680 cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc gacaggacta 16740 taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt tccgaccctg 16800 ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct ttctcatagc 16860 tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg ctgtgtgcac 16920 gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct tgagtccaac 16980 ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat tagcagagcg 17040 aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg ctacactaga 17100 aggacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa aagagttggt 17160 agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt ttgcaagcag 17220 cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc tacggggtct 17280 gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt atcaaaaagg 17340 atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta aagtatatat 17400 gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat ctcagcgatc 17460 tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac tacgatacgg 17520 gagggcttac catctggccc cagtgctgca atgataccgc gagacccacg ctcaccggct 17580 ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag tggtcctgca 17640 actttatccg cctccatcca gtctattaat tgttgccggg aagctagagt aagtagttcg 17700 ccagttaata gtttgcgcaa cgttgttgcc attgctacag gcatcgtggt gtcacgctcg 17760 tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt tacatgatcc 17820 cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt cagaagtaag 17880 ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct tactgtcatg 17940 ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt ctgagaatag 18000 tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatac cgcgccacat 18060 agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa actctcaagg 18120 atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa ctgatcttca 18180 gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca aaatgccgca 18240 aaaaagggaa taagggcgac acggaaatgt tgaatactca t 18281 <210> 12 <211> 17936 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 12 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcgtttaaac ttaagcttgg taccgagctc ggatccacta 1560 gtccagtgtg gtggaattcc tgcttcgcga tgtacgggcc agatatacgc gttgacattg 1620 attattgact agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat 1680 ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc 1740 ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca 1800 ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta 1860 tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 1920 tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 1980 cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 2040 ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggaacca 2100 aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 2160 taggcgtgta cggtgggagg tctatataag cagagctctc cctatcagtg atagagatct 2220 ccctatcagt gatagagatc gtcgacgagc tcgtttagtg aaccgtcaga tcgcctggag 2280 acgccatcca cgctgttttg acctccatag aagacaccgg gaccgatcca gcctccggac 2340 tctagcgttt aaacttaagc ttgccaccat ggccagtcgg gaagaggagc agcgcgaaac 2400 cacccccgag cgcggacgcg gtgcggcgcg acgtccccca accatggagg acgtgtcgtc 2460 cccgtccccg tcgccgccgc ctccccgggc gcccccaaaa aagcggatga ggcggcgtat 2520 cgagtccgag gacgaggaag actcatcaca agacgcgctg gtgccgcgca cacccagccc 2580 gcggccatcg acctcggcgg cggatttggc cattgcgccc aagaagaaaa agaagcgccc 2640 ttctcccaag cccgagcgcc cgccatcacc agaggtaatc gtggacagcg aggaagaaag 2700 agaagatgtg gcgctacaaa tggtgggttt cagcaaccca ccggtgctaa tcaagcatgg 2760 caaaggaggt aagcgcacag tgcggcggct gaatgaagac gacccagtgg cgcgtggtat 2820 gcggacgcaa gaggaagagg aagagcccag cgaagcggaa agtgaaatta cggtgatgaa 2880 cccgctgagt gtgccgatcg tgtctgcgtg ggagaagggc atggaggctg cgcgcgcgct 2940 gatggacaag taccacgtgg ataacgatct aaaggcgaac ttcaaactac tgcctgacca 3000 agtggaagct ctggcggccg tatgcaagac ctggctgaac gaggagcacc gcgggttgca 3060 gctgaccttc accagcaaca agacctttgt gacgatgatg gggcgattcc tgcaggcgta 3120 cctgcagtcg tttgcagagg tgacctacaa gcatcacgag cccacgggct gcgcgttgtg 3180 gctgcaccgc tgcgctgaga tcgaaggcga gcttaagtgt ctacacggaa gcattatgat 3240 aaataaggag cacgtgattg aaatggatgt gacgagcgaa aacgggcagc gcgcgctgaa 3300 ggagcagtct agcaaggcca agatcgtgaa gaaccggtgg ggccgaaatg tggtgcagat 3360 ctccaacacc gacgcaaggt gctgcgtgca cgacgcggcc tgtccggcca atcagttttc 3420 cggcaagtct tgcggcatgt tcttctctga aggcgcaaag gctcaggtgg cttttaagca 3480 gatcaaggct tttatgcagg cgctgtatcc taacgcccag accgggcacg gtcacctttt 3540 gatgccacta cggtgcgagt gcaactcaaa gcctgggcac gcgccctttt tgggaaggca 3600 gctaccaaag ttgactccgt tcgccctgag caacgcggag gacctggacg cggatctgat 3660 ctccgacaag agcgtgctgg ccagcgtgca ccacccggcg ctgatagtgt tccagtgctg 3720 caaccctgtg tatcgcaact cgcgcgcgca gggcggaggc cccaactgcg acttcaagat 3780 atcggcgccc gacctgctaa acgcgttggt gatggtgcgc agcctgtgga gtgaaaactt 3840 caccgagctg ccgcggatgg ttgtgcctga gtttaagtgg agcactaaac accagtatcg 3900 caacgtgtcc ctgccagtgg cgcatagcga tgcgcggcag aacccctttg atttttaacc 3960 cgggagttct agggatctgc ccctctccct cccccccccc taacgttact ggccgaagcc 4020 gcttggaata aggccggtgt gcgtttgtct atatgttatt ttccaccata ttgccgtctt 4080 ttggcaatgt gagggcccgg aaacctggcc ctgtcttctt gacgagcatt cctaggggtc 4140 tttcccctct cgccaaagga atgcaaggtc tgttgaatgt cgtgaaggaa gcagttcctc 4200 tggaagcttc ttgaagacaa acaacgtctg tagcgaccct ttgcaggcag cggaaccccc 4260 cacctggcga caggtgcctc tgcggccaaa agccacgtgt ataagataca cctgcaaagg 4320 cggcacaacc ccagtgccac gttgtgagtt ggatagttgt ggaaagagtc aaatggctct 4380 cctcaagcgt attcaacaag gggctgaagg atgcccagaa ggtaccccat tgtatgggat 4440 ctgatctggg gcctcggtgc acatgcttta catgtgttta gtcgaggtta aaaaaacgtc 4500 taggcccccc gaaccacggg gacgtggttt tcctttgaaa aacacgatga taaggatcca 4560 ccggaggcca ccatgactac gtccggcgtt ccatttggca tgacactacg accaacacga 4620 tctcggttgt ctcggcgcac tccgtacagt agggatcgtc tacctccttt tgagacagaa 4680 acccgcgcta ccatactgga ggatcatccg ctgctgcccg aatgtaacac tttgacaatg 4740 cacaacgtga gttacgtgcg aggtcttccc tgcagtgtgg gatttacgct gattcaggaa 4800 tgggttgttc cctgggatat ggttctaacg cgggaggagc ttgtaatcct gaggaagtgt 4860 atgcacgtgt gcctgtgttg tgccaacatt gatatcatga cgagcatgat gatccatggt 4920 tacgagtcct gggctctcca ctgtcattgt tccagtcccg gttccctgca gtgtatagcc 4980 ggcgggcagg ttttggccag ctggtttagg atggtggtgg atggcgccat gtttaatcag 5040 aggtttatat ggtaccggga ggtggtgaat tacaacatgc caaaagaggt aatgtttatg 5100 tccagcgtgt ttatgagggg tcgccactta atctacctgc gcttgtggta tgatggccac 5160 gtgggttctg tggtccccgc catgagcttt ggatacagcg ccttgcactg tgggattttg 5220 aacaatattg tggtgctgtg ctgcagttac tgtgctgatt taagtgagat cagggtgcgc 5280 tgctgtgccc ggaggacaag gcgccttatg ctgcgggcgg tgcgaatcat cgctgaggag 5340 accactgcca tgttgtattc ctgcaggacg gagcggcggc ggcagcagtt tattcgcgcg 5400 ctgctgcagc accaccgccc tatcctgatg cacgattatg actctacccc catgtaggcg 5460 gccgctcgag tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag 5520 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 5580 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 5640 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 5700 caggcatgct ggggatgcgg tgggctctat ggcttctgag gcggaaagaa ccagctgggg 5760 ctctaggggg tatccccggg gttggggttg cgccttttcc aaggcatcca gcacagtggc 5820 ggccgcaata tttgcatgtc gctatgtgtt ctgggaaatc accataaacg tgaaatccct 5880 atcagtgata gagacttata agttccctat cagtgataga gaaccggtgg gcactcttcc 5940 gtggtctggt ggataaattc gcaagggtat catggcggac gaccggggtt cgagccccgt 6000 atccggccgt ccgccgtgat ccatgcggtt accgcccgcg tgtcgaaccc aggtgtgcga 6060 cgtcagacaa cgggggagtg ctcctttttg aattccactt tggccgcggc tcgagggggt 6120 tggggttgcg ccttttccaa ggcagccctg ggtttgcgca gggacgcggc tgctctgggc 6180 gtggttccgg gaaacgcagc ggcgccgacc ctgggtctcg cacattcttc acgtccgttc 6240 gcagcgtcac ccggatcttc gccgctaccc ttgtgggccc cccggcgacg cttcctgctc 6300 cgcccctaag tcgggaaggt tccttgcggt tcgcggcgtg ccggacgtga caaacggaag 6360 ccgcacgtct cactagtacc ctcgcagacg gacagcgcca gggagcaatg gcagcgcgcc 6420 gaccgcgatg ggctgtggcc aatagcggct gctcagcagg gcgcgccgag agcagcggcc 6480 gggaaggggc ggtgcgggag gcggggtgtg gggcggtagt gtgggccctg ttcctgcccg 6540 cgcggtgttc cgcattctgc aagcctccgg agcgcacgtc ggcagtcggc tccctcgttg 6600 accgaatcac cgacctctct ccccaggggg atctgtgagt ttggggaccc ttgattgttc 6660 tttctttttc gctattgtaa aattcatgtt atatggaggg ggcaaagttt tcagggtgtt 6720 gtttagaatg ggaagatgtc ccttgtatca ccatggaccc tcatgataat tttgtttctt 6780 tcactttcta ctctgttgac aaccattgtc tcctcttatt ttcttttcat tttctgtaac 6840 tttttcgtta aactttagct tgcatttgta acgaattttt aaattcactt ttgtttattt 6900 gtcagattgt aagtactttc tctaatcact tttttttcaa ggcaatcagg gtatattata 6960 ttgtacttca gcacagtttt agagaacaat tgttataatt aaatgataag gtagaatatt 7020 tctgcatata aattctggct ggcgtggaaa tattcttatt ggtagaaaca actacatcct 7080 ggtcatcatc ctgcctttct ctttatggtt acaatgatat acactgtttg agatgaggat 7140 aaaatactct gagtccaaac cgggcccctc tgctaaccat gttcatgcct tcttcttttt 7200 cctacagctc ctgggcaacg tgctggttat tgtgctgtct catcattttg gcaaagaatt 7260 gtaatacgac tcactatagg gcgagccacc atggctagat tagataaaag taaagtgatt 7320 aacagcgcat tagagctgct taatgaggtc ggaatcgaag gtttaacaac ccgtaaactc 7380 gcccagaagc taggtgtaga gcagcctaca ttgtattggc atgtaaaaaa taagcgggct 7440 ttgctcgacg ccttagccat tgagatgtta gataggcacc atactcactt ttgcccttta 7500 gaaggggaaa gctggcaaga ttttttacgt aataacgcta aaagttttag atgtgcttta 7560 ctaagtcatc gcgatggagc aaaagtacat ttaggtacac ggcctacaga aaaacagtat 7620 gaaactctcg aaaatcaatt agccttttta tgccaacaag gtttttcact agagaatgcc 7680 ttatatgcac tcagcgccgt ggggcatttt actttaggtt gcgtattgga agatcaagag 7740 catcaagtcg ctaaagaaga aagggaaaca cctactactg atagtatgcc gccattatta 7800 cgacaagcta tcgaattatt tgatcaccaa ggtgcagagc cagccttctt attcggcctt 7860 gaattgatca tatgcggatt agaaaaacaa cttaaatgtg aaagtgggtc cccaaaaaag 7920 aagagaaagg tcgacggcgg tggttcagtt taagcgtaca gcggctcccg ggagttctag 7980 ggatctgccc ctctccctcc ccccccccta acgttactgg ccgaagccgc ttggaataag 8040 gccggtgtgc gtttgtctat atgttatttt ccaccatatt gccgtctttt ggcaatgtga 8100 gggcccggaa acctggccct gtcttcttga cgagcattcc taggggtctt tcccctctcg 8160 ccaaaggaat gcaaggtctg ttgaatgtcg tgaaggaagc agttcctctg gaagcttctt 8220 gaagacaaac aacgtctgta gcgacccttt gcaggcagcg gaacccccca cctggcgaca 8280 ggtgcctctg cggccaaaag ccacgtgtat aagatacacc tgcaaaggcg gcacaacccc 8340 agtgccacgt tgtgagttgg atagttgtgg aaagagtcaa atggctctcc tcaagcgtat 8400 tcaacaaggg gctgaaggat gcccagaagg taccccattg tatgggatct gatctggggc 8460 ctcggtgcac atgctttaca tgtgtttagt cgaggttaaa aaaacgtcta ggccccccga 8520 accacgggga cgtggttttc ctttgaaaaa cacgatgata aggatccacc ggaggccacc 8580 atgaccgagt acaagcccac ggtgcgcctc gccacccgcg acgacgtccc cagggccgta 8640 cgcaccctcg ccgccgcgtt cgccgactac cccgccacgc gccacaccgt cgatccggac 8700 cgccacatcg agcgggtcac cgagctgcaa gaactcttcc tcacgcgcgt cgggctcgac 8760 atcggcaagg tgtgggtcgc ggacgacggc gccgcggtgg cggtctggac cacgccggag 8820 agcgtcgaag cgggggcggt gttcgccgag atcggcccgc gcatggccga gttgagcggt 8880 tcccggctgg ccgcgcagca acagatggaa ggcctcctgg cgccgcaccg gcccaaggag 8940 cccgcgtggt tcctggccac cgtcggcgtc tcgcccgacc accagggcaa gggtctgggc 9000 agcgccgtcg tgctccccgg agtggaggcg gccgagcgcg ccggggtgcc cgccttcctg 9060 gagacctccg cgccccgcaa cctccccttc tacgagcggc tcggcttcac cgtcaccgcc 9120 gacgtcgagg tgcccgaagg accgcgcacc tggtgcatga cccgcaagcc cggtgcctga 9180 ccgcgtctgg aacaatcaac ctctggatta caaaatttgt gaaagattga ctggtattct 9240 taactatgtt gctcctttta cgctatgtgg atacgctgct ttaatgcctt tgtatcatgc 9300 tattgcttcc cgtatggctt tcattttctc ctccttgtat aaatcctggt tgctgtctct 9360 ttatgaggag ttgtggcccg ttgtcaggca acgtggcgtg gtgtgcactg tgtttgctga 9420 cgcaaccccc actggttggg gcattgccac cacctgtcag ctcctttccg ggactttcgc 9480 tttccccctc cctattgcca cggcggaact catcgccgcc tgccttgccc gctgctggac 9540 aggggctcgg ctgttgggca ctgacaattc cgtggtgttg tcggggaagc tgacgtcctt 9600 tccatggctg ctcgcctgtg ttgccacctg gattctgcgc gggacgtcct tctgctacgt 9660 cccttcggcc ctcaatccag cggaccttcc ttcccgcggc ctgctgccgg ctctgcggcc 9720 tcttccgcgt cttcgccttc gccctcagac gagtcggatc tccctttggg ccgcctcccc 9780 gcaaaatgac cgaccaagcg acgcccaacc tgccatcacg agatttcgat tccaccgccg 9840 ccttctatga aaggttgggc ttcggaatcg ttttccggga cgccggctgg atgatcctcc 9900 agcgcgggga tctcatgctg gagttcttcg cccaccccaa cttgtttatt gcagcttata 9960 atggttacaa ataaagcaat agcatcacaa atttcacaaa taaagcattt ttttcactgc 10020 attctagttg tggtttgtcc aaactcatca atgtatctta tcatgtctgt agctgatcaa 10080 ttggcgcgcc gaattcgtta tctgcagaat tcggcttggc ggctgcgcgt tcaaacctcc 10140 cgcttcaaaa tggagaccct gcgtgctcac tcgggcttaa atacccagcg tgaccacatg 10200 gtgtcgcaaa atgtcgcaaa acactcacgt gacctctaat acaggacctc tagagcatgg 10260 aaactagata agaaagaaat acgcagagac caaagttcaa ctgaaacgaa ttaaacggtt 10320 tattgattaa caagcaaact agtttacaga ttacgggtga ggtaacgggt gccgatgggg 10380 cgaggctcag aataaacgcc atttgtgtca acagcaaagt ccacatttgt agatttgttg 10440 tagttggaag tgtattgaat ctctgggttc cagcgtttgc tgttttcttt ctgcagctcc 10500 cattcaattt ccacgctgac ctgtccggtg ctgtactgcg tgatgaacga cgcaaactta 10560 gctggactga aggtagttgg aggattcgcg ggaacaggtg tattcttaat caggatctga 10620 ggaggcgggt gtttcagtcc aaagcctccc atcagcggcg agggatgaaa gtgtccgtcc 10680 gtgtgaggaa tcttggccca gataggaccc tgcaggtaca cgtcccggtc ctgccagacc 10740 atgccaggta aggctccttg actgttgacg gtccctgtag caggagcggt gttggccgat 10800 tgcaggttag tggccaccgt gccgtactct tctgtggcca ctgggttggt ggttttaatt 10860 tcttcctcgt tggttatcat aacgttgtca aggtccacgt tgctatttcc agctccctgt 10920 ttcccaaata ttaagactcc gctcatcgga aaaaatttgt cttcgtcgtc cttgtgggtt 10980 gccatagcgg gaccgggatt taccagagag tctctgccat tcagatgata cttggtggca 11040 ccggtccagg caaagttgct gttgttattt tgattggttg tcttggagac gcgttgctgc 11100 cggtagcagg gcccgggtag ccagtttttg gcctgattcg ccatgctact aggcccggcc 11160 tgagaaaatt gcaacgtccg atttcctgcg gtaccactcg tggtctgagt ccgagacagg 11220 tagtacaggt actggtcgat gagggggttc atcagccggt ccaggctttg gctgtgcgcg 11280 tagctgctgt gaaaaggcac gtcctcaaac gtgtagctga actgaaagtt gttgcccgtt 11340 ctcagcattt gagaaggaaa gtattccagg cagtagaagg aggaacggcc cacggcctga 11400 ctgccattgt tcagagtcag gtacccgtac tgaggaatca tgaagacgtc cgccgggaac 11460 ggaggcaggc agccctggtg cgcagagccg aggacgtacg ggagctggta ttccgagtcc 11520 gtaaagacct gaaccgtgct ggtaaggtta ttggcgatgg tcgtggtgcc atcattcgtc 11580 gtgacctcct tgacctggat gttgaagagc ttgaagttga gcttcttggg ccggaatccc 11640 cagttgttgt tgatgagtcg ctgccagtca cgtggtgaga agtggcagtg gaatctgtta 11700 aagtcaaaat acccccaggg ggtgctgtag ccgaagtagg tgttgtcgtt ggtgctgcct 11760 cccgattggc tggagatttg cttgtagagg tggttgttgt aggtggggag ggcccaggtt 11820 cgggtgctgg tggtgatgac tctgtcgccc agccatgtgg aatcgcaatg ccaatttcct 11880 gaggcgttac ccactccgtc ggcgccttcg ttattgtctg ccattggagc gccaccgcct 11940 gcagccattg tattagatcc cacaccagag ggggctgcgg ggggttctcc gagtggttga 12000 gggtcgggca ctgactctga gtcgccagtc tgcccaaagt tgagtctctt tctcgcgggc 12060 tgctggcctt tcttgccgat gcccgaagag gagtctggtt cctggggtga ttgctctacc 12120 ggtctcttct ttccaggagc cgtcttagcg ccttcctcaa ccagaccgag aggttcgaga 12180 acccgcttct tggcctggaa gactgctcgc ccgaggttgc ccccaaaaga cgtatcttct 12240 tgcagacgct cctgaaactc ggcgtcggcg tggttatacc gcaggtacgg attgtcaccc 12300 gctttgagct gctggtcgta ggccttgtcg tgctcgaggg ccgctgcgtc cgccgcgttg 12360 acgggctccc ccttgtcgag tccgttgaag ggtccgaggt acttgtagcc aggaagcacc 12420 agaccccggc cgtcgtcctg cttttgctgg ttggctttgg gtttcggggc tccaggtttc 12480 aagtcccacc actcgcgaat gccctcagag aggttgtcct cgagccaatc tggaagataa 12540 ccatcggcag ccatacctga tttaaatcat ttattgttca aagatgcagt catccaaatc 12600 cacattgacc agatcgcagg cagtgcaagc gtctggcacc tttcccatga tatgatgaat 12660 gtagcacagt ttctgatacg cctttttgac gacagaaacg ggttgagatt ctgacacggg 12720 aaagcactct aaacagtctt tctgtccgtg agtgaagcag atatttgaat tctgattcat 12780 tctctcgcat tgtctgcagg gaaacagcat cagattcatg cccacgtgac gagaacattt 12840 gttttggtac ctgtctgcgt agttgatcga agcttccgcg tctgacgtcg atggctgcgc 12900 aactgactcg cgcacccgtt tgggctcact tatatctgcg tcactggggg cgggtctttt 12960 cttggctcca ccctttttga cgtagaattc atgctccacc tcaaccacgt gatcctttgc 13020 ccaccggaaa aagtctttga cttcctgctt ggtgaccttc ccaaagtcat gatccagacg 13080 gcgggtgagt tcaaatttga acatccggtc ttgcaacggc tgctggtgtt cgaaggtcgt 13140 tgagttcccg tcaatcacgg cgcacatgtt ggtgttggag gtgacgatca cgggagtcgg 13200 gtctatctgg gccgaggact tgcatttctg gtccacgcgc accttgcttc ctccgagaat 13260 ggctttggcc gactccacga ccttggcggt catcttcccc tcctcccacc agatcaccat 13320 cttgtcgaca cagtcgttga agggaaagtt ctcattggtc cagtttacgc acccgtagaa 13380 gggcacagtg tgggctatgg cctccgcgat gttggtcttc ccggtagttg caggcccaaa 13440 cagccagatg gtgttcctct tgccgaactt tttcgtggcc catcccagaa agacggaagc 13500 cgcatattgg ggatcgtacc cgtttagttc caaaatttta taaatccgat tgctggaaat 13560 gtcctccacg ggctgctggc ccaccaggta gtcgggggcg gttttagtca ggctcataat 13620 ctttcccgca ttgtccaagg cagccttgat ttgggaccgc gagttggagg ccgcattgaa 13680 ggagatgtat gaggcctggt cctcctggat ccactgcttc tccgaggtaa tccccttgtc 13740 cacgagccac ccgaccagct ccatgtacct ggctgaagtt tttgatctga tcaccggcgc 13800 atcagaattg ggattctgat tctctttgtt ctgctcctgc gtctgcgaca cgtgcgtcag 13860 atgctgcgcc accaaccgtt tacgctccgt gagattcaaa caggcgctgt ggagagaaag 13920 gcaaagtgga tgtcagtatc tctatcactg atagggagat ctctatcact gatagggaac 13980 ttaccttaaa tactgttcca tattagtcca cgcccactgg agctcaggct gggttttggg 14040 gagcaagtaa ttggggatgt agcactcatc caccaccttg ttcccgcctc cggcgccatt 14100 tctggtcttt gtgaccgcga accagtttgg caaagtcggc tcgatcccgc ggtaaattct 14160 ctgaatcagt ttttcgcgaa tctgactcag gaaacgtccc aaaaccatgg atttcacccc 14220 ggtggtttcc acgagcacgt gcatgtggaa gtagctctct cccttctcaa attgcacaaa 14280 gaaaagagcc tccggggcct tactcacacg gcgccattcc gtcagaaagt cgcgctgcag 14340 cttctcggcc acggtcaggg gtgcctgctc aatcagattc agatccatgt cagaatctgg 14400 cggcaactcc cattccttct cggccaccca gttcacaaag ctgtcagaaa tgccgggcag 14460 atgctcgtca aggtcgctgg ggaccttaat cacaatctcg taaaaccccg gcatggcggc 14520 tgcgcgttca aacctcccgc ttcaaaatgg agaccctgcg tgctcactcg ggcgatctct 14580 atcactgata gggagatctc tatcactgat agggagatta aatagaatgg ctaggatccg 14640 gccggcctgc aggtgtcctc acaggaacga agtccctaaa gaaacagtgg cagccaggtt 14700 tagccccgga attgactgga ttcctttttt agggcccatt ggtatggctt tttccccgta 14760 tccccccagg tgtctgcagg ctcaaagagc agcgagaagc gttcagagga aagcgatccc 14820 gtgccacctt ccccgtgccc gggctgtccc cgcacgctgc cggctcgggg atgcgggggg 14880 agcgccggac cggagcggag ccccgggcgg ctcgctgctg ccccctagcg ggggagggac 14940 gtaattacat ccctgggggc tttggggggg ggctgtccct ctagagcggc cgccaccgcg 15000 gtggagctcc agcttttgtt ccctttagtg agggttaatt agatcttaat acgactcact 15060 atagggcgaa ttgggtaccg ggccccccct cgaggtcgac ggtatcgata agcttgatat 15120 ctataacaag aaaatatata tataataagt tatcacgtaa gtagaacatg aaataacaat 15180 ataattatcg tatgagttaa atcttaaaag tcacgtaaaa gataatcatg cgtcattttg 15240 actcacgcgg tcgttatagt tcaaaatcag tgacacttac cgcattgaca agcacgcctc 15300 acgggagctc caagcggcga ctgagatgtc ctaaatgcac agcgacggat tcgcgctatt 15360 tagaaagaga gagcaatatt tcaagaatgc atgcgtcaat tttacgcaga ctatctttct 15420 agggttaatc tagctgcatc aggatcatat cgtcgggtct tttttccggc tcagtcatcg 15480 cccaagctgg cgctatctgg gcatcgggga ggaagaagcc cgtgcctttt cccgcgaggt 15540 tgaagcggca tggaaagagt ttgccgagga tgactgctgc tgcattgacg ttgagcgaaa 15600 acgcacgttt accatgatga ttcgggaagg tgtggccatg cacgccttta acggtgaact 15660 gttcgttcag gccacctggg ataccagttc gtcgcggctt ttccggacac agttccggat 15720 ggtcagcccg aagcgcatca gcaacccgaa caataccggc gacagccgga actgccgtgc 15780 cggtgtgcag attaatgaca gcggtgcggc gctgggatat tacgtcagcg aggacgggta 15840 tcctggctgg atgccgcaga aatggacatg gataccccgt gagttacccg gcgggcgcgc 15900 ttggcgtaat catggtcata gctgtttcct gtgtgaaatt gttatccgct cacaattcca 15960 cacaacatac gagccggaag cataaagtgt aaagcctggg gtgcctaatg agtgagctaa 16020 ctcacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag 16080 ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc 16140 gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct 16200 cactcaaagg cggtaatacg gttatccaca gaatcagggg ataacgcagg aaagaacatg 16260 tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc 16320 cataggctcc gcccccctga cgagcatcac aaaaatcgac gctcaagtca gaggtggcga 16380 aacccgacag gactataaag ataccaggcg tttccccctg gaagctccct cgtgcgctct 16440 cctgttccga ccctgccgct taccggatac ctgtccgcct ttctcccttc gggaagcgtg 16500 gcgctttctc atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag 16560 ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct gcgccttatc cggtaactat 16620 cgtcttgagt ccaacccggt aagacacgac ttatcgccac tggcagcagc cactggtaac 16680 aggattagca gagcgaggta tgtaggcggt gctacagagt tcttgaagtg gtggcctaac 16740 tacggctaca ctagaaggac agtatttggt atctgcgctc tgctgaagcc agttaccttc 16800 ggaaaaagag ttggtagctc ttgatccggc aaacaaacca ccgctggtag cggtggtttt 16860 tttgtttgca agcagcagat tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc 16920 ttttctacgg ggtctgacgc tcagtggaac gaaaactcac gttaagggat tttggtcatg 16980 agattatcaa aaaggatctt cacctagatc cttttaaatt aaaaatgaag ttttaaatca 17040 atctaaagta tatatgagta aacttggtct gacagttacc aatgcttaat cagtgaggca 17100 cctatctcag cgatctgtct atttcgttca tccatagttg cctgactccc cgtcgtgtag 17160 ataactacga tacgggaggg cttaccatct ggccccagtg ctgcaatgat accgcgagac 17220 ccacgctcac cggctccaga tttatcagca ataaaccagc cagccggaag ggccgagcgc 17280 agaagtggtc ctgcaacttt atccgcctcc atccagtcta ttaattgttg ccgggaagct 17340 agagtaagta gttcgccagt taatagtttg cgcaacgttg ttgccattgc tacaggcatc 17400 gtggtgtcac gctcgtcgtt tggtatggct tcattcagct ccggttccca acgatcaagg 17460 cgagttacat gatcccccat gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc 17520 gttgtcagaa gtaagttggc cgcagtgtta tcactcatgg ttatggcagc actgcataat 17580 tctcttactg tcatgccatc cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag 17640 tcattctgag aatagtgtat gcggcgaccg agttgctctt gcccggcgtc aatacgggat 17700 aataccgcgc cacatagcag aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg 17760 cgaaaactct caaggatctt accgctgttg agatccagtt cgatgtaacc cactcgtgca 17820 cccaactgat cttcagcatc ttttactttc accagcgttt ctgggtgagc aaaaacagga 17880 aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga aatgttgaat actcat 17936 <210> 13 <211> 21391 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 13 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcgtttaaac ttaagcttgg taccgagctc ggatccacta 1560 gtccagtgtg gtggaattcc tgcttcgcga tgtacgggcc agatatacgc gttgacattg 1620 attattgact agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat 1680 ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc 1740 ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca 1800 ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta 1860 tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 1920 tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 1980 cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 2040 ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggaacca 2100 aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 2160 taggcgtgta cggtgggagg tctatataag cagagctctc cctatcagtg atagagatct 2220 ccctatcagt gatagagatc gtcgacgagc tcgtttagtg aaccgtcaga tcgcctggag 2280 acgccatcca cgctgttttg acctccatag aagacaccgg gaccgatcca gcctccggac 2340 tctagcgttt aaacttaagc ttgccaccat ggccagtcgg gaagaggagc agcgcgaaac 2400 cacccccgag cgcggacgcg gtgcggcgcg acgtccccca accatggagg acgtgtcgtc 2460 cccgtccccg tcgccgccgc ctccccgggc gcccccaaaa aagcggatga ggcggcgtat 2520 cgagtccgag gacgaggaag actcatcaca agacgcgctg gtgccgcgca cacccagccc 2580 gcggccatcg acctcggcgg cggatttggc cattgcgccc aagaagaaaa agaagcgccc 2640 ttctcccaag cccgagcgcc cgccatcacc agaggtaatc gtggacagcg aggaagaaag 2700 agaagatgtg gcgctacaaa tggtgggttt cagcaaccca ccggtgctaa tcaagcatgg 2760 caaaggaggt aagcgcacag tgcggcggct gaatgaagac gacccagtgg cgcgtggtat 2820 gcggacgcaa gaggaagagg aagagcccag cgaagcggaa agtgaaatta cggtgatgaa 2880 cccgctgagt gtgccgatcg tgtctgcgtg ggagaagggc atggaggctg cgcgcgcgct 2940 gatggacaag taccacgtgg ataacgatct aaaggcgaac ttcaaactac tgcctgacca 3000 agtggaagct ctggcggccg tatgcaagac ctggctgaac gaggagcacc gcgggttgca 3060 gctgaccttc accagcaaca agacctttgt gacgatgatg gggcgattcc tgcaggcgta 3120 cctgcagtcg tttgcagagg tgacctacaa gcatcacgag cccacgggct gcgcgttgtg 3180 gctgcaccgc tgcgctgaga tcgaaggcga gcttaagtgt ctacacggaa gcattatgat 3240 aaataaggag cacgtgattg aaatggatgt gacgagcgaa aacgggcagc gcgcgctgaa 3300 ggagcagtct agcaaggcca agatcgtgaa gaaccggtgg ggccgaaatg tggtgcagat 3360 ctccaacacc gacgcaaggt gctgcgtgca cgacgcggcc tgtccggcca atcagttttc 3420 cggcaagtct tgcggcatgt tcttctctga aggcgcaaag gctcaggtgg cttttaagca 3480 gatcaaggct tttatgcagg cgctgtatcc taacgcccag accgggcacg gtcacctttt 3540 gatgccacta cggtgcgagt gcaactcaaa gcctgggcac gcgccctttt tgggaaggca 3600 gctaccaaag ttgactccgt tcgccctgag caacgcggag gacctggacg cggatctgat 3660 ctccgacaag agcgtgctgg ccagcgtgca ccacccggcg ctgatagtgt tccagtgctg 3720 caaccctgtg tatcgcaact cgcgcgcgca gggcggaggc cccaactgcg acttcaagat 3780 atcggcgccc gacctgctaa acgcgttggt gatggtgcgc agcctgtgga gtgaaaactt 3840 caccgagctg ccgcggatgg ttgtgcctga gtttaagtgg agcactaaac accagtatcg 3900 caacgtgtcc ctgccagtgg cgcatagcga tgcgcggcag aacccctttg atttttaacc 3960 cgggagttct agggatctgc ccctctccct cccccccccc taacgttact ggccgaagcc 4020 gcttggaata aggccggtgt gcgtttgtct atatgttatt ttccaccata ttgccgtctt 4080 ttggcaatgt gagggcccgg aaacctggcc ctgtcttctt gacgagcatt cctaggggtc 4140 tttcccctct cgccaaagga atgcaaggtc tgttgaatgt cgtgaaggaa gcagttcctc 4200 tggaagcttc ttgaagacaa acaacgtctg tagcgaccct ttgcaggcag cggaaccccc 4260 cacctggcga caggtgcctc tgcggccaaa agccacgtgt ataagataca cctgcaaagg 4320 cggcacaacc ccagtgccac gttgtgagtt ggatagttgt ggaaagagtc aaatggctct 4380 cctcaagcgt attcaacaag gggctgaagg atgcccagaa ggtaccccat tgtatgggat 4440 ctgatctggg gcctcggtgc acatgcttta catgtgttta gtcgaggtta aaaaaacgtc 4500 taggcccccc gaaccacggg gacgtggttt tcctttgaaa aacacgatga taaggatcca 4560 ccggaggcca ccatgactac gtccggcgtt ccatttggca tgacactacg accaacacga 4620 tctcggttgt ctcggcgcac tccgtacagt agggatcgtc tacctccttt tgagacagaa 4680 acccgcgcta ccatactgga ggatcatccg ctgctgcccg aatgtaacac tttgacaatg 4740 cacaacgtga gttacgtgcg aggtcttccc tgcagtgtgg gatttacgct gattcaggaa 4800 tgggttgttc cctgggatat ggttctaacg cgggaggagc ttgtaatcct gaggaagtgt 4860 atgcacgtgt gcctgtgttg tgccaacatt gatatcatga cgagcatgat gatccatggt 4920 tacgagtcct gggctctcca ctgtcattgt tccagtcccg gttccctgca gtgtatagcc 4980 ggcgggcagg ttttggccag ctggtttagg atggtggtgg atggcgccat gtttaatcag 5040 aggtttatat ggtaccggga ggtggtgaat tacaacatgc caaaagaggt aatgtttatg 5100 tccagcgtgt ttatgagggg tcgccactta atctacctgc gcttgtggta tgatggccac 5160 gtgggttctg tggtccccgc catgagcttt ggatacagcg ccttgcactg tgggattttg 5220 aacaatattg tggtgctgtg ctgcagttac tgtgctgatt taagtgagat cagggtgcgc 5280 tgctgtgccc ggaggacaag gcgccttatg ctgcgggcgg tgcgaatcat cgctgaggag 5340 accactgcca tgttgtattc ctgcaggacg gagcggcggc ggcagcagtt tattcgcgcg 5400 ctgctgcagc accaccgccc tatcctgatg cacgattatg actctacccc catgtaggcg 5460 gccgctcgag tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag 5520 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 5580 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 5640 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 5700 caggcatgct ggggatgcgg tgggctctat ggcttctgag gcggaaagaa ccagctgggg 5760 ctctaggggg tatccccggg gttggggttg cgccttttcc aaggcatcca gcacagtggc 5820 ggccgcaata tttgcatgtc gctatgtgtt ctgggaaatc accataaacg tgaaatccct 5880 atcagtgata gagacttata agttccctat cagtgataga gaaccggtgg gcactcttcc 5940 gtggtctggt ggataaattc gcaagggtat catggcggac gaccggggtt cgagccccgt 6000 atccggccgt ccgccgtgat ccatgcggtt accgcccgcg tgtcgaaccc aggtgtgcga 6060 cgtcagacaa cgggggagtg ctcctttttg aattccactt tggccgcggc tcgagggggt 6120 tggggttgcg ccttttccaa ggcagccctg ggtttgcgca gggacgcggc tgctctgggc 6180 gtggttccgg gaaacgcagc ggcgccgacc ctgggtctcg cacattcttc acgtccgttc 6240 gcagcgtcac ccggatcttc gccgctaccc ttgtgggccc cccggcgacg cttcctgctc 6300 cgcccctaag tcgggaaggt tccttgcggt tcgcggcgtg ccggacgtga caaacggaag 6360 ccgcacgtct cactagtacc ctcgcagacg gacagcgcca gggagcaatg gcagcgcgcc 6420 gaccgcgatg ggctgtggcc aatagcggct gctcagcagg gcgcgccgag agcagcggcc 6480 gggaaggggc ggtgcgggag gcggggtgtg gggcggtagt gtgggccctg ttcctgcccg 6540 cgcggtgttc cgcattctgc aagcctccgg agcgcacgtc ggcagtcggc tccctcgttg 6600 accgaatcac cgacctctct ccccaggggg atctgtgagt ttggggaccc ttgattgttc 6660 tttctttttc gctattgtaa aattcatgtt atatggaggg ggcaaagttt tcagggtgtt 6720 gtttagaatg ggaagatgtc ccttgtatca ccatggaccc tcatgataat tttgtttctt 6780 tcactttcta ctctgttgac aaccattgtc tcctcttatt ttcttttcat tttctgtaac 6840 tttttcgtta aactttagct tgcatttgta acgaattttt aaattcactt ttgtttattt 6900 gtcagattgt aagtactttc tctaatcact tttttttcaa ggcaatcagg gtatattata 6960 ttgtacttca gcacagtttt agagaacaat tgttataatt aaatgataag gtagaatatt 7020 tctgcatata aattctggct ggcgtggaaa tattcttatt ggtagaaaca actacatcct 7080 ggtcatcatc ctgcctttct ctttatggtt acaatgatat acactgtttg agatgaggat 7140 aaaatactct gagtccaaac cgggcccctc tgctaaccat gttcatgcct tcttcttttt 7200 cctacagctc ctgggcaacg tgctggttat tgtgctgtct catcattttg gcaaagaatt 7260 gtaatacgac tcactatagg gcgagccacc atggctagat tagataaaag taaagtgatt 7320 aacagcgcat tagagctgct taatgaggtc ggaatcgaag gtttaacaac ccgtaaactc 7380 gcccagaagc taggtgtaga gcagcctaca ttgtattggc atgtaaaaaa taagcgggct 7440 ttgctcgacg ccttagccat tgagatgtta gataggcacc atactcactt ttgcccttta 7500 gaaggggaaa gctggcaaga ttttttacgt aataacgcta aaagttttag atgtgcttta 7560 ctaagtcatc gcgatggagc aaaagtacat ttaggtacac ggcctacaga aaaacagtat 7620 gaaactctcg aaaatcaatt agccttttta tgccaacaag gtttttcact agagaatgcc 7680 ttatatgcac tcagcgccgt ggggcatttt actttaggtt gcgtattgga agatcaagag 7740 catcaagtcg ctaaagaaga aagggaaaca cctactactg atagtatgcc gccattatta 7800 cgacaagcta tcgaattatt tgatcaccaa ggtgcagagc cagccttctt attcggcctt 7860 gaattgatca tatgcggatt agaaaaacaa cttaaatgtg aaagtgggtc cccaaaaaag 7920 aagagaaagg tcgacggcgg tggtgctttg tctcctcagc actctgctgt cactcaagga 7980 agtatcatca agaacaagga gggcatggat gctaagtcac taactgcctg gtcccggaca 8040 ctggtgacct tcaaggatgt atttgtggac ttcaccaggg aggagtggaa gctgctggac 8100 actgctcagc agatcgtgta cagaaatgtg atgctggaga actataagaa cctggtttcc 8160 ttgggttatc agcttactaa gccagatgtg atcctccggt tggagaaggg agaagagccc 8220 tggctggtgg agagagaaat tcaccaagag acccatcctg attcagagac tgcatttgaa 8280 atcaaatcat cagtttaagc gtacagcggc tcccgggagt tctagggatc tgcccctctc 8340 cctccccccc ccctaacgtt actggccgaa gccgcttgga ataaggccgg tgtgcgtttg 8400 tctatatgtt attttccacc atattgccgt cttttggcaa tgtgagggcc cggaaacctg 8460 gccctgtctt cttgacgagc attcctaggg gtctttcccc tctcgccaaa ggaatgcaag 8520 gtctgttgaa tgtcgtgaag gaagcagttc ctctggaagc ttcttgaaga caaacaacgt 8580 ctgtagcgac cctttgcagg cagcggaacc ccccacctgg cgacaggtgc ctctgcggcc 8640 aaaagccacg tgtataagat acacctgcaa aggcggcaca accccagtgc cacgttgtga 8700 gttggatagt tgtggaaaga gtcaaatggc tctcctcaag cgtattcaac aaggggctga 8760 aggatgccca gaaggtaccc cattgtatgg gatctgatct ggggcctcgg tgcacatgct 8820 ttacatgtgt ttagtcgagg ttaaaaaaac gtctaggccc cccgaaccac ggggacgtgg 8880 ttttcctttg aaaaacacga tgataaggat ccaccggagg ccaccatgac cgagtacaag 8940 cccacggtgc gcctcgccac ccgcgacgac gtccccaggg ccgtacgcac cctcgccgcc 9000 gcgttcgccg actaccccgc cacgcgccac accgtcgatc cggaccgcca catcgagcgg 9060 gtcaccgagc tgcaagaact cttcctcacg cgcgtcgggc tcgacatcgg caaggtgtgg 9120 gtcgcggacg acggcgccgc ggtggcggtc tggaccacgc cggagagcgt cgaagcgggg 9180 gcggtgttcg ccgagatcgg cccgcgcatg gccgagttga gcggttcccg gctggccgcg 9240 cagcaacaga tggaaggcct cctggcgccg caccggccca aggagcccgc gtggttcctg 9300 gccaccgtcg gcgtctcgcc cgaccaccag ggcaagggtc tgggcagcgc cgtcgtgctc 9360 cccggagtgg aggcggccga gcgcgccggg gtgcccgcct tcctggagac ctccgcgccc 9420 cgcaacctcc ccttctacga gcggctcggc ttcaccgtca ccgccgacgt cgaggtgccc 9480 gaaggaccgc gcacctggtg catgacccgc aagcccggtg cctgaccgcg tctggaacaa 9540 tcaacctctg gattacaaaa tttgtgaaag attgactggt attcttaact atgttgctcc 9600 ttttacgcta tgtggatacg ctgctttaat gcctttgtat catgctattg cttcccgtat 9660 ggctttcatt ttctcctcct tgtataaatc ctggttgctg tctctttatg aggagttgtg 9720 gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt gctgacgcaa cccccactgg 9780 ttggggcatt gccaccacct gtcagctcct ttccgggact ttcgctttcc ccctccctat 9840 tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc tggacagggg ctcggctgtt 9900 gggcactgac aattccgtgg tgttgtcggg gaagctgacg tcctttccat ggctgctcgc 9960 ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt cggccctcaa 10020 tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc cgcgtcttcg 10080 ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgcaaa atgaccgacc 10140 aagcgacgcc caacctgcca tcacgagatt tcgattccac cgccgccttc tatgaaaggt 10200 tgggcttcgg aatcgttttc cgggacgccg gctggatgat cctccagcgc ggggatctca 10260 tgctggagtt cttcgcccac cccaacttgt ttattgcagc ttataatggt tacaaataaa 10320 gcaatagcat cacaaatttc acaaataaag catttttttc actgcattct agttgtggtt 10380 tgtccaaact catcaatgta tcttatcatg tctgtagctg atcaattggc gcgccgaatt 10440 cgttatctgc agaattcggc ttggcggctg cgcgttcaaa cctcccgctt caaaatggag 10500 accctgcgtg ctcactcggg cttaaatacc cagcgtgacc acatggtgtc gcaaaatgtc 10560 gcaaaacact cacgtgacct ctaatacagg acctctagag catggaaact agataagaaa 10620 gaaatacgca gagaccaaag ttcaactgaa acgaattaaa cggtttattg attaacaagc 10680 aaactagttt acagattacg ggtgaggtaa cgggtgccga tggggcgagg ctcagaataa 10740 acgccatttg tgtcaacagc aaagtccaca tttgtagatt tgttgtagtt ggaagtgtat 10800 tgaatctctg ggttccagcg tttgctgttt tctttctgca gctcccattc aatttccacg 10860 ctgacctgtc cggtgctgta ctgcgtgatg aacgacgcaa acttagctgg actgaaggta 10920 gttggaggat tcgcgggaac aggtgtattc ttaatcagga tctgaggagg cgggtgtttc 10980 agtccaaagc ctcccatcag cggcgaggga tgaaagtgtc cgtccgtgtg aggaatcttg 11040 gcccagatag gaccctgcag gtacacgtcc cggtcctgcc agaccatgcc aggtaaggct 11100 ccttgactgt tgacggtccc tgtagcagga gcggtgttgg ccgattgcag gttagtggcc 11160 accgtgccgt actcttctgt ggccactggg ttggtggttt taatttcttc ctcgttggtt 11220 atcataacgt tgtcaaggtc cacgttgcta tttccagctc cctgtttccc aaatattaag 11280 actccgctca tcggaaaaaa tttgtcttcg tcgtccttgt gggttgccat agcgggaccg 11340 ggatttacca gagagtctct gccattcaga tgatacttgg tggcaccggt ccaggcaaag 11400 ttgctgttgt tattttgatt ggttgtcttg gagacgcgtt gctgccggta gcagggcccg 11460 ggtagccagt ttttggcctg attcgccatg ctactaggcc cggcctgaga aaattgcaac 11520 gtccgatttc ctgcggtacc actcgtggtc tgagtccgag acaggtagta caggtactgg 11580 tcgatgaggg ggttcatcag ccggtccagg ctttggctgt gcgcgtagct gctgtgaaaa 11640 ggcacgtcct caaacgtgta gctgaactga aagttgttgc ccgttctcag catttgagaa 11700 ggaaagtatt ccaggcagta gaaggaggaa cggcccacgg cctgactgcc attgttcaga 11760 gtcaggtacc cgtactgagg aatcatgaag acgtccgccg ggaacggagg caggcagccc 11820 tggtgcgcag agccgaggac gtacgggagc tggtattccg agtccgtaaa gacctgaacc 11880 gtgctggtaa ggttattggc gatggtcgtg gtgccatcat tcgtcgtgac ctccttgacc 11940 tggatgttga agagcttgaa gttgagcttc ttgggccgga atccccagtt gttgttgatg 12000 agtcgctgcc agtcacgtgg tgagaagtgg cagtggaatc tgttaaagtc aaaatacccc 12060 cagggggtgc tgtagccgaa gtaggtgttg tcgttggtgc tgcctcccga ttggctggag 12120 atttgcttgt agaggtggtt gttgtaggtg gggagggccc aggttcgggt gctggtggtg 12180 atgactctgt cgcccagcca tgtggaatcg caatgccaat ttcctgaggc gttacccact 12240 ccgtcggcgc cttcgttatt gtctgccatt ggagcgccac cgcctgcagc cattgtatta 12300 gatcccacac cagagggggc tgcggggggt tctccgagtg gttgagggtc gggcactgac 12360 tctgagtcgc cagtctgccc aaagttgagt ctctttctcg cgggctgctg gcctttcttg 12420 ccgatgcccg aagaggagtc tggttcctgg ggtgattgct ctaccggtct cttctttcca 12480 ggagccgtct tagcgccttc ctcaaccaga ccgagaggtt cgagaacccg cttcttggcc 12540 tggaagactg ctcgcccgag gttgccccca aaagacgtat cttcttgcag acgctcctga 12600 aactcggcgt cggcgtggtt ataccgcagg tacggattgt cacccgcttt gagctgctgg 12660 tcgtaggcct tgtcgtgctc gagggccgct gcgtccgccg cgttgacggg ctcccccttg 12720 tcgagtccgt tgaagggtcc gaggtacttg tagccaggaa gcaccagacc ccggccgtcg 12780 tcctgctttt gctggttggc tttgggtttc ggggctccag gtttcaagtc ccaccactcg 12840 cgaatgccct cagagaggtt gtcctcgagc caatctggaa gataaccatc ggcagccata 12900 cctgatttaa atcatttatt gttcaaagat gcagtcatcc aaatccacat tgaccagatc 12960 gcaggcagtg caagcgtctg gcacctttcc catgatatga tgaatgtagc acagtttctg 13020 atacgccttt ttgacgacag aaacgggttg agattctgac acgggaaagc actctaaaca 13080 gtctttctgt ccgtgagtga agcagatatt tgaattctga ttcattctct cgcattgtct 13140 gcagggaaac agcatcagat tcatgcccac gtgacgagaa catttgtttt ggtacctgtc 13200 tgcgtagttg atcgaagctt ccgcgtctga cgtcgatggc tgcgcaactg actcgcgcac 13260 ccgtttgggc tcacttatat ctgcgtcact gggggcgggt cttttcttgg ctccaccctt 13320 tttgacgtag aattcatgct ccacctcaac cacgtgatcc tttgcccacc ggaaaaagtc 13380 tttgacttcc tgcttggtga ccttcccaaa gtcatgatcc agacggcggg tgagttcaaa 13440 tttgaacatc cggtcttgca acggctgctg gtgttcgaag gtcgttgagt tcccgtcaat 13500 cacggcgcac atgttggtgt tggaggtgac gatcacggga gtcgggtcta tctgggccga 13560 ggacttgcat ttctggtcca cgcgcacctt gcttcctccg agaatggctt tggccgactc 13620 cacgaccttg gcggtcatct tcccctcctc ccaccagatc accatcttgt cgacacagtc 13680 gttgaaggga aagttctcat tggtccagtt tacgcacccg tagaagggca cagtgtgggc 13740 tatggcctcc gcgatgttgg tcttcccggt agttgcaggc ccaaacagcc agatggtgtt 13800 cctcttgccg aactttttcg tggcccatcc cagaaagacg gaagccgcat attggggatc 13860 gtacccgttt agttccaaaa ttttataaat ccgattgctg gaaatgtcct ccacgggctg 13920 ctggcccacc aggtagtcgg gggcggtttt agtcaggctc ataatctttc ccgcattgtc 13980 caaggcagcc ttgatttggg accgcgagtt ggaggccgca ttgaaggaga tgtatgaggc 14040 ctggtcctcc tggatccact gcttctccga ggtaatcccc ttgtccacga gccacccgac 14100 cagctccatg tacctggctg aagtttttga tctgatcacc ggcgcatcag aattgggatt 14160 ctgattctct ttgttctgct cctgcgtctg cgacacgtgc gtcagatgct gcgccaccaa 14220 ccgtttacgc tccgtgagat tcaaacaggc gctgtggaga gaaaggcaaa gtggatgtca 14280 gtatctctat cactgatagg gagatctcta tcactgatag ggaacttacc ttaaatactg 14340 ttccatatta gtccacgccc actggagctc aggctgggtt ttggggagca agtaattggg 14400 gatgtagcac tcatccacca ccttgttccc gcctccggcg ccatttctgg tctttgtgac 14460 cgcgaaccag tttggcaaag tcggctcgat cccgcggtaa attctctgaa tcagtttttc 14520 gcgaatctga ctcaggaaac gtcccaaaac catggatttc accccggtgg tttccacgag 14580 cacgtgcatg tggaagtagc tctctccctt ctcaaattgc acaaagaaaa gagcctccgg 14640 ggccttactc acacggcgcc attccgtcag aaagtcgcgc tgcagcttct cggccacggt 14700 caggggtgcc tgctcaatca gattcagatc catgtcagaa tctggcggca actcccattc 14760 cttctcggcc acccagttca caaagctgtc agaaatgccg ggcagatgct cgtcaaggtc 14820 gctggggacc ttaatcacaa tctcgtaaaa ccccggcatg gcggctgcgc gttcaaacct 14880 cccgcttcaa aatggagacc ctgcgtgctc actcgggcga tctctatcac tgatagggag 14940 atctctatca ctgataggga gattaaatag aatggctagg atccggccgg cctgcaggtg 15000 tcctcacagg aacgaagtcc ctaaagaaac agtggcagcc aggtttagcc ccggaattga 15060 ctggattcct tttttagggc ccattggtat ggctttttcc ccgtatcccc ccaggtgtct 15120 gcaggctcaa agagcagcga gaagcgttca gaggaaagcg atcccgtgcc accttccccg 15180 tgcccgggct gtccccgcac gctgccggct cggggatgcg gggggagcgc cggaccggag 15240 cggagccccg ggcggctcgc tgctgccccc tagcggggga gggacgtaat tacatccctg 15300 ggggctttgg gggggggctg tccctctaga gcggccgcca ccgcggtgga gctccagctt 15360 ttgttccctt tagtgagggt taattagatc ttaatacgac tcactatagg gcgaattggg 15420 taccgggccc cccctcgagg tcgacggtat cgcctccaag gccagcttcc cacaataagt 15480 tgggtgaatt ttggctcatt cctcctttct ataggattga ggtcagagct ttgtgatggg 15540 aattctgtgg aatgtgtgtc agttagggtg tggaaagtcc cgcgatcgct agcaaacgcc 15600 agcaacgcgg cctttttacg gttcctggcc ttttgctggc cttttgctca catgtcctgc 15660 aggcagctgc gcgctcgctc gctcactgag gccgcccggg caaagcccgg gcgtcgggcg 15720 acctttggtc gcccggcctc agtgagcgag cgagcgcgca gagagggagt ggccaactcc 15780 atcactaggg gttcctgcgg ccgcacgcgt ggagctagtt attaatagta atcaattacg 15840 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 15900 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 15960 atagtaacgt caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 16020 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 16080 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 16140 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 16200 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 16260 gtcaatggga gtttgttttg caccaaaatc aacgggactt tccaaaatgt cgtaacaact 16320 ccgccccatt gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag 16380 ctcgtttagt gaaccgtcag atcgcctgga gacgccatcc acgctgtttt gacctccata 16440 gaagacaccg ggaccgatcc agcctccgcg gattcgaatc ccggccggga acggtgcatt 16500 ggaacgcgga ttccccgtgc caagagtgac gtaagtaccg cctatagagt ctataggccc 16560 acaaaaaatg ctttcttctt ttaatatact tttttgttta tcttatttct aatactttcc 16620 ctaatctctt tctttcaggg caataatgat acaatgtatc atgcctcttt gcaccattct 16680 aaagaataac agtgataatt tctgggttaa ggcaatagca atatttctgc atataaatat 16740 ttctgcatat aaattgtaac tgatgtaaga ggtttcatat tgctaatagc agctacaatc 16800 cagctaccat tctgctttta ttttatggtt gggataaggc tggattattc tgagtccaag 16860 ctaggccctt ttgctaatca tgttcatacc tcttatcttc ctcccacagc tcctgggcaa 16920 cgtgctggtc tgtgtgctgg cccatcactt tggcaaagaa ttgggattcg aacatcgatt 16980 gaattctgaa tggtgagcaa gggcgaggag ctgttcaccg gggtggtgcc catcctggtc 17040 gagctggacg gcgacgtaaa cggccacaag ttcagcgtgt ccggcgaggg cgagggcgat 17100 gccacctacg gcaagctgac cctgaagttc atctgcacca ccggcaagct gcccgtgccc 17160 tggcccaccc tcgtgaccac cctgacctac ggcgtgcagt gcttcagccg ctaccccgac 17220 cacatgaagc agcacgactt cttcaagtcc gccatgcccg aaggctacgt ccaggagcgc 17280 accatcttct tcaaggacga cggcaactac aagacccgcg ccgaggtgaa gttcgagggc 17340 gacaccctgg tgaaccgcat cgagctgaag ggcatcgact tcaaggagga cggcaacatc 17400 ctggggcaca agctggagta caactacaac agccacaacg tctatatcat ggccgacaag 17460 cagaagaacg gcatcaaggt gaacttcaag atccgccaca acatcgagga cggcagcgtg 17520 cagctcgccg accactacca gcagaacacc cccatcggcg acggccccgt gctgctgccc 17580 gacaaccact acctgagcac ccagtccgcc ctgagcaaag accccaacga gaagcgcgat 17640 cacatggtcc tgctggagtt cgtgaccgcc gccgggatca ctctcggcat ggacgagctg 17700 tacaagtact cagatctcga gctcaagtag ggatcctcta gagtcgacct gcagaagctt 17760 gcctcgagca gcgctgctcg agagatctac gggtggcatc cctgtgaccc ctccccagtg 17820 cctctcctgg ccctggaagt tgccactcca gtgcccacca gccttgtcct aataaaatta 17880 agttgcatca ttttgtctga ctaggtgtcc ttctataata ttatggggtg gaggggggtg 17940 gtatggagca aggggcaagt tgggaagaca acctgtaggg cctgcggggt ctattgggaa 18000 ccaagctgga gtgcagtggc acaatcttgg ctcactgcaa tctccgcctc ctgggttcaa 18060 gcgattctcc tgcctcagcc tcccgagttg ttgggattcc aggcatgcat gaccaggctc 18120 agctaatttt tgtttttttg gtagagacgg ggtttcacca tattggccag gctggtctcc 18180 aactcctaat ctcaggtgat ctacccacct tggcctccca aattgctggg attacaggcg 18240 tgaaccactg ctcccttccc tgtccttctg attttgtagg taaccacgtg cggaccgagc 18300 ggccgcagga acccctagtg atggagttgg ccactccctc tctgcgcgct cgctcgctca 18360 ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt tgcccgggcg gcctcagtga 18420 gcgagcgagc gcgcagctgc ctgcaggggc gcctgatgcg gtattttctc cttacgcatc 18480 tgtgcggtat ttcacaccgc atacgtcgta gctgatcaat tggcgcgccg aattcgttaa 18540 caagctttaa ttaacgcgta cgataagctt gatatctata acaagaaaat atatatataa 18600 taagttatca cgtaagtaga acatgaaata acaatataat tatcgtatga gttaaatctt 18660 aaaagtcacg taaaagataa tcatgcgtca ttttgactca cgcggtcgtt atagttcaaa 18720 atcagtgaca cttaccgcat tgacaagcac gcctcacggg agctccaagc ggcgactgag 18780 atgtcctaaa tgcacagcga cggattcgcg ctatttagaa agagagagca atatttcaag 18840 aatgcatgcg tcaattttac gcagactatc tttctagggt taatctagct gcatcaggat 18900 catatcgtcg ggtctttttt ccggctcagt catcgcccaa gctggcgcta tctgggcatc 18960 ggggaggaag aagcccgtgc cttttcccgc gaggttgaag cggcatggaa agagtttgcc 19020 gaggatgact gctgctgcat tgacgttgag cgaaaacgca cgtttaccat gatgattcgg 19080 gaaggtgtgg ccatgcacgc ctttaacggt gaactgttcg ttcaggccac ctgggatacc 19140 agttcgtcgc ggcttttccg gacacagttc cggatggtca gcccgaagcg catcagcaac 19200 ccgaacaata ccggcgacag ccggaactgc cgtgccggtg tgcagattaa tgacagcggt 19260 gcggcgctgg gatattacgt cagcgaggac gggtatcctg gctggatgcc gcagaaatgg 19320 acatggatac cccgtgagtt acccggcggg cgcgcttggc gtaatcatgg tcatagctgt 19380 ttcctgtgtg aaattgttat ccgctcacaa ttccacacaa catacgagcc ggaagcataa 19440 agtgtaaagc ctggggtgcc taatgagtga gctaactcac attaattgcg ttgcgctcac 19500 tgcccgcttt ccagtcggga aacctgtcgt gccagctgca ttaatgaatc ggccaacgcg 19560 cggggagagg cggtttgcgt attgggcgct cttccgcttc ctcgctcact gactcgctgc 19620 gctcggtcgt tcggctgcgg cgagcggtat cagctcactc aaaggcggta atacggttat 19680 ccacagaatc aggggataac gcaggaaaga acatgtgagc aaaaggccag caaaaggcca 19740 ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag gctccgcccc cctgacgagc 19800 atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc gacaggacta taaagatacc 19860 aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt tccgaccctg ccgcttaccg 19920 gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct ttctcatagc tcacgctgta 19980 ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg ctgtgtgcac gaaccccccg 20040 ttcagcccga ccgctgcgcc ttatccggta actatcgtct tgagtccaac ccggtaagac 20100 acgacttatc gccactggca gcagccactg gtaacaggat tagcagagcg aggtatgtag 20160 gcggtgctac agagttcttg aagtggtggc ctaactacgg ctacactaga aggacagtat 20220 ttggtatctg cgctctgctg aagccagtta ccttcggaaa aagagttggt agctcttgat 20280 ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt ttgcaagcag cagattacgc 20340 gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc tacggggtct gacgctcagt 20400 ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt atcaaaaagg atcttcacct 20460 agatcctttt aaattaaaaa tgaagtttta aatcaatcta aagtatatat gagtaaactt 20520 ggtctgacag ttaccaatgc ttaatcagtg aggcacctat ctcagcgatc tgtctatttc 20580 gttcatccat agttgcctga ctccccgtcg tgtagataac tacgatacgg gagggcttac 20640 catctggccc cagtgctgca atgataccgc gagacccacg ctcaccggct ccagatttat 20700 cagcaataaa ccagccagcc ggaagggccg agcgcagaag tggtcctgca actttatccg 20760 cctccatcca gtctattaat tgttgccggg aagctagagt aagtagttcg ccagttaata 20820 gtttgcgcaa cgttgttgcc attgctacag gcatcgtggt gtcacgctcg tcgtttggta 20880 tggcttcatt cagctccggt tcccaacgat caaggcgagt tacatgatcc cccatgttgt 20940 gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt cagaagtaag ttggccgcag 21000 tgttatcact catggttatg gcagcactgc ataattctct tactgtcatg ccatccgtaa 21060 gatgcttttc tgtgactggt gagtactcaa ccaagtcatt ctgagaatag tgtatgcggc 21120 gaccgagttg ctcttgcccg gcgtcaatac gggataatac cgcgccacat agcagaactt 21180 taaaagtgct catcattgga aaacgttctt cggggcgaaa actctcaagg atcttaccgc 21240 tgttgagatc cagttcgatg taacccactc gtgcacccaa ctgatcttca gcatctttta 21300 ctttcaccag cgtttctggg tgagcaaaaa caggaaggca aaatgccgca aaaaagggaa 21360 taagggcgac acggaaatgt tgaatactca t 21391 <210> 14 <211> 21046 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 14 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcgtttaaac ttaagcttgg taccgagctc ggatccacta 1560 gtccagtgtg gtggaattcc tgcttcgcga tgtacgggcc agatatacgc gttgacattg 1620 attattgact agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat 1680 ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc 1740 ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca 1800 ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta 1860 tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 1920 tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 1980 cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 2040 ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggaacca 2100 aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 2160 taggcgtgta cggtgggagg tctatataag cagagctctc cctatcagtg atagagatct 2220 ccctatcagt gatagagatc gtcgacgagc tcgtttagtg aaccgtcaga tcgcctggag 2280 acgccatcca cgctgttttg acctccatag aagacaccgg gaccgatcca gcctccggac 2340 tctagcgttt aaacttaagc ttgccaccat ggccagtcgg gaagaggagc agcgcgaaac 2400 cacccccgag cgcggacgcg gtgcggcgcg acgtccccca accatggagg acgtgtcgtc 2460 cccgtccccg tcgccgccgc ctccccgggc gcccccaaaa aagcggatga ggcggcgtat 2520 cgagtccgag gacgaggaag actcatcaca agacgcgctg gtgccgcgca cacccagccc 2580 gcggccatcg acctcggcgg cggatttggc cattgcgccc aagaagaaaa agaagcgccc 2640 ttctcccaag cccgagcgcc cgccatcacc agaggtaatc gtggacagcg aggaagaaag 2700 agaagatgtg gcgctacaaa tggtgggttt cagcaaccca ccggtgctaa tcaagcatgg 2760 caaaggaggt aagcgcacag tgcggcggct gaatgaagac gacccagtgg cgcgtggtat 2820 gcggacgcaa gaggaagagg aagagcccag cgaagcggaa agtgaaatta cggtgatgaa 2880 cccgctgagt gtgccgatcg tgtctgcgtg ggagaagggc atggaggctg cgcgcgcgct 2940 gatggacaag taccacgtgg ataacgatct aaaggcgaac ttcaaactac tgcctgacca 3000 agtggaagct ctggcggccg tatgcaagac ctggctgaac gaggagcacc gcgggttgca 3060 gctgaccttc accagcaaca agacctttgt gacgatgatg gggcgattcc tgcaggcgta 3120 cctgcagtcg tttgcagagg tgacctacaa gcatcacgag cccacgggct gcgcgttgtg 3180 gctgcaccgc tgcgctgaga tcgaaggcga gcttaagtgt ctacacggaa gcattatgat 3240 aaataaggag cacgtgattg aaatggatgt gacgagcgaa aacgggcagc gcgcgctgaa 3300 ggagcagtct agcaaggcca agatcgtgaa gaaccggtgg ggccgaaatg tggtgcagat 3360 ctccaacacc gacgcaaggt gctgcgtgca cgacgcggcc tgtccggcca atcagttttc 3420 cggcaagtct tgcggcatgt tcttctctga aggcgcaaag gctcaggtgg cttttaagca 3480 gatcaaggct tttatgcagg cgctgtatcc taacgcccag accgggcacg gtcacctttt 3540 gatgccacta cggtgcgagt gcaactcaaa gcctgggcac gcgccctttt tgggaaggca 3600 gctaccaaag ttgactccgt tcgccctgag caacgcggag gacctggacg cggatctgat 3660 ctccgacaag agcgtgctgg ccagcgtgca ccacccggcg ctgatagtgt tccagtgctg 3720 caaccctgtg tatcgcaact cgcgcgcgca gggcggaggc cccaactgcg acttcaagat 3780 atcggcgccc gacctgctaa acgcgttggt gatggtgcgc agcctgtgga gtgaaaactt 3840 caccgagctg ccgcggatgg ttgtgcctga gtttaagtgg agcactaaac accagtatcg 3900 caacgtgtcc ctgccagtgg cgcatagcga tgcgcggcag aacccctttg atttttaacc 3960 cgggagttct agggatctgc ccctctccct cccccccccc taacgttact ggccgaagcc 4020 gcttggaata aggccggtgt gcgtttgtct atatgttatt ttccaccata ttgccgtctt 4080 ttggcaatgt gagggcccgg aaacctggcc ctgtcttctt gacgagcatt cctaggggtc 4140 tttcccctct cgccaaagga atgcaaggtc tgttgaatgt cgtgaaggaa gcagttcctc 4200 tggaagcttc ttgaagacaa acaacgtctg tagcgaccct ttgcaggcag cggaaccccc 4260 cacctggcga caggtgcctc tgcggccaaa agccacgtgt ataagataca cctgcaaagg 4320 cggcacaacc ccagtgccac gttgtgagtt ggatagttgt ggaaagagtc aaatggctct 4380 cctcaagcgt attcaacaag gggctgaagg atgcccagaa ggtaccccat tgtatgggat 4440 ctgatctggg gcctcggtgc acatgcttta catgtgttta gtcgaggtta aaaaaacgtc 4500 taggcccccc gaaccacggg gacgtggttt tcctttgaaa aacacgatga taaggatcca 4560 ccggaggcca ccatgactac gtccggcgtt ccatttggca tgacactacg accaacacga 4620 tctcggttgt ctcggcgcac tccgtacagt agggatcgtc tacctccttt tgagacagaa 4680 acccgcgcta ccatactgga ggatcatccg ctgctgcccg aatgtaacac tttgacaatg 4740 cacaacgtga gttacgtgcg aggtcttccc tgcagtgtgg gatttacgct gattcaggaa 4800 tgggttgttc cctgggatat ggttctaacg cgggaggagc ttgtaatcct gaggaagtgt 4860 atgcacgtgt gcctgtgttg tgccaacatt gatatcatga cgagcatgat gatccatggt 4920 tacgagtcct gggctctcca ctgtcattgt tccagtcccg gttccctgca gtgtatagcc 4980 ggcgggcagg ttttggccag ctggtttagg atggtggtgg atggcgccat gtttaatcag 5040 aggtttatat ggtaccggga ggtggtgaat tacaacatgc caaaagaggt aatgtttatg 5100 tccagcgtgt ttatgagggg tcgccactta atctacctgc gcttgtggta tgatggccac 5160 gtgggttctg tggtccccgc catgagcttt ggatacagcg ccttgcactg tgggattttg 5220 aacaatattg tggtgctgtg ctgcagttac tgtgctgatt taagtgagat cagggtgcgc 5280 tgctgtgccc ggaggacaag gcgccttatg ctgcgggcgg tgcgaatcat cgctgaggag 5340 accactgcca tgttgtattc ctgcaggacg gagcggcggc ggcagcagtt tattcgcgcg 5400 ctgctgcagc accaccgccc tatcctgatg cacgattatg actctacccc catgtaggcg 5460 gccgctcgag tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag 5520 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 5580 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 5640 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 5700 caggcatgct ggggatgcgg tgggctctat ggcttctgag gcggaaagaa ccagctgggg 5760 ctctaggggg tatccccggg gttggggttg cgccttttcc aaggcatcca gcacagtggc 5820 ggccgcaata tttgcatgtc gctatgtgtt ctgggaaatc accataaacg tgaaatccct 5880 atcagtgata gagacttata agttccctat cagtgataga gaaccggtgg gcactcttcc 5940 gtggtctggt ggataaattc gcaagggtat catggcggac gaccggggtt cgagccccgt 6000 atccggccgt ccgccgtgat ccatgcggtt accgcccgcg tgtcgaaccc aggtgtgcga 6060 cgtcagacaa cgggggagtg ctcctttttg aattccactt tggccgcggc tcgagggggt 6120 tggggttgcg ccttttccaa ggcagccctg ggtttgcgca gggacgcggc tgctctgggc 6180 gtggttccgg gaaacgcagc ggcgccgacc ctgggtctcg cacattcttc acgtccgttc 6240 gcagcgtcac ccggatcttc gccgctaccc ttgtgggccc cccggcgacg cttcctgctc 6300 cgcccctaag tcgggaaggt tccttgcggt tcgcggcgtg ccggacgtga caaacggaag 6360 ccgcacgtct cactagtacc ctcgcagacg gacagcgcca gggagcaatg gcagcgcgcc 6420 gaccgcgatg ggctgtggcc aatagcggct gctcagcagg gcgcgccgag agcagcggcc 6480 gggaaggggc ggtgcgggag gcggggtgtg gggcggtagt gtgggccctg ttcctgcccg 6540 cgcggtgttc cgcattctgc aagcctccgg agcgcacgtc ggcagtcggc tccctcgttg 6600 accgaatcac cgacctctct ccccaggggg atctgtgagt ttggggaccc ttgattgttc 6660 tttctttttc gctattgtaa aattcatgtt atatggaggg ggcaaagttt tcagggtgtt 6720 gtttagaatg ggaagatgtc ccttgtatca ccatggaccc tcatgataat tttgtttctt 6780 tcactttcta ctctgttgac aaccattgtc tcctcttatt ttcttttcat tttctgtaac 6840 tttttcgtta aactttagct tgcatttgta acgaattttt aaattcactt ttgtttattt 6900 gtcagattgt aagtactttc tctaatcact tttttttcaa ggcaatcagg gtatattata 6960 ttgtacttca gcacagtttt agagaacaat tgttataatt aaatgataag gtagaatatt 7020 tctgcatata aattctggct ggcgtggaaa tattcttatt ggtagaaaca actacatcct 7080 ggtcatcatc ctgcctttct ctttatggtt acaatgatat acactgtttg agatgaggat 7140 aaaatactct gagtccaaac cgggcccctc tgctaaccat gttcatgcct tcttcttttt 7200 cctacagctc ctgggcaacg tgctggttat tgtgctgtct catcattttg gcaaagaatt 7260 gtaatacgac tcactatagg gcgagccacc atggctagat tagataaaag taaagtgatt 7320 aacagcgcat tagagctgct taatgaggtc ggaatcgaag gtttaacaac ccgtaaactc 7380 gcccagaagc taggtgtaga gcagcctaca ttgtattggc atgtaaaaaa taagcgggct 7440 ttgctcgacg ccttagccat tgagatgtta gataggcacc atactcactt ttgcccttta 7500 gaaggggaaa gctggcaaga ttttttacgt aataacgcta aaagttttag atgtgcttta 7560 ctaagtcatc gcgatggagc aaaagtacat ttaggtacac ggcctacaga aaaacagtat 7620 gaaactctcg aaaatcaatt agccttttta tgccaacaag gtttttcact agagaatgcc 7680 ttatatgcac tcagcgccgt ggggcatttt actttaggtt gcgtattgga agatcaagag 7740 catcaagtcg ctaaagaaga aagggaaaca cctactactg atagtatgcc gccattatta 7800 cgacaagcta tcgaattatt tgatcaccaa ggtgcagagc cagccttctt attcggcctt 7860 gaattgatca tatgcggatt agaaaaacaa cttaaatgtg aaagtgggtc cccaaaaaag 7920 aagagaaagg tcgacggcgg tggttcagtt taagcgtaca gcggctcccg ggagttctag 7980 ggatctgccc ctctccctcc ccccccccta acgttactgg ccgaagccgc ttggaataag 8040 gccggtgtgc gtttgtctat atgttatttt ccaccatatt gccgtctttt ggcaatgtga 8100 gggcccggaa acctggccct gtcttcttga cgagcattcc taggggtctt tcccctctcg 8160 ccaaaggaat gcaaggtctg ttgaatgtcg tgaaggaagc agttcctctg gaagcttctt 8220 gaagacaaac aacgtctgta gcgacccttt gcaggcagcg gaacccccca cctggcgaca 8280 ggtgcctctg cggccaaaag ccacgtgtat aagatacacc tgcaaaggcg gcacaacccc 8340 agtgccacgt tgtgagttgg atagttgtgg aaagagtcaa atggctctcc tcaagcgtat 8400 tcaacaaggg gctgaaggat gcccagaagg taccccattg tatgggatct gatctggggc 8460 ctcggtgcac atgctttaca tgtgtttagt cgaggttaaa aaaacgtcta ggccccccga 8520 accacgggga cgtggttttc ctttgaaaaa cacgatgata aggatccacc ggaggccacc 8580 atgaccgagt acaagcccac ggtgcgcctc gccacccgcg acgacgtccc cagggccgta 8640 cgcaccctcg ccgccgcgtt cgccgactac cccgccacgc gccacaccgt cgatccggac 8700 cgccacatcg agcgggtcac cgagctgcaa gaactcttcc tcacgcgcgt cgggctcgac 8760 atcggcaagg tgtgggtcgc ggacgacggc gccgcggtgg cggtctggac cacgccggag 8820 agcgtcgaag cgggggcggt gttcgccgag atcggcccgc gcatggccga gttgagcggt 8880 tcccggctgg ccgcgcagca acagatggaa ggcctcctgg cgccgcaccg gcccaaggag 8940 cccgcgtggt tcctggccac cgtcggcgtc tcgcccgacc accagggcaa gggtctgggc 9000 agcgccgtcg tgctccccgg agtggaggcg gccgagcgcg ccggggtgcc cgccttcctg 9060 gagacctccg cgccccgcaa cctccccttc tacgagcggc tcggcttcac cgtcaccgcc 9120 gacgtcgagg tgcccgaagg accgcgcacc tggtgcatga cccgcaagcc cggtgcctga 9180 ccgcgtctgg aacaatcaac ctctggatta caaaatttgt gaaagattga ctggtattct 9240 taactatgtt gctcctttta cgctatgtgg atacgctgct ttaatgcctt tgtatcatgc 9300 tattgcttcc cgtatggctt tcattttctc ctccttgtat aaatcctggt tgctgtctct 9360 ttatgaggag ttgtggcccg ttgtcaggca acgtggcgtg gtgtgcactg tgtttgctga 9420 cgcaaccccc actggttggg gcattgccac cacctgtcag ctcctttccg ggactttcgc 9480 tttccccctc cctattgcca cggcggaact catcgccgcc tgccttgccc gctgctggac 9540 aggggctcgg ctgttgggca ctgacaattc cgtggtgttg tcggggaagc tgacgtcctt 9600 tccatggctg ctcgcctgtg ttgccacctg gattctgcgc gggacgtcct tctgctacgt 9660 cccttcggcc ctcaatccag cggaccttcc ttcccgcggc ctgctgccgg ctctgcggcc 9720 tcttccgcgt cttcgccttc gccctcagac gagtcggatc tccctttggg ccgcctcccc 9780 gcaaaatgac cgaccaagcg acgcccaacc tgccatcacg agatttcgat tccaccgccg 9840 ccttctatga aaggttgggc ttcggaatcg ttttccggga cgccggctgg atgatcctcc 9900 agcgcgggga tctcatgctg gagttcttcg cccaccccaa cttgtttatt gcagcttata 9960 atggttacaa ataaagcaat agcatcacaa atttcacaaa taaagcattt ttttcactgc 10020 attctagttg tggtttgtcc aaactcatca atgtatctta tcatgtctgt agctgatcaa 10080 ttggcgcgcc gaattcgtta tctgcagaat tcggcttggc ggctgcgcgt tcaaacctcc 10140 cgcttcaaaa tggagaccct gcgtgctcac tcgggcttaa atacccagcg tgaccacatg 10200 gtgtcgcaaa atgtcgcaaa acactcacgt gacctctaat acaggacctc tagagcatgg 10260 aaactagata agaaagaaat acgcagagac caaagttcaa ctgaaacgaa ttaaacggtt 10320 tattgattaa caagcaaact agtttacaga ttacgggtga ggtaacgggt gccgatgggg 10380 cgaggctcag aataaacgcc atttgtgtca acagcaaagt ccacatttgt agatttgttg 10440 tagttggaag tgtattgaat ctctgggttc cagcgtttgc tgttttcttt ctgcagctcc 10500 cattcaattt ccacgctgac ctgtccggtg ctgtactgcg tgatgaacga cgcaaactta 10560 gctggactga aggtagttgg aggattcgcg ggaacaggtg tattcttaat caggatctga 10620 ggaggcgggt gtttcagtcc aaagcctccc atcagcggcg agggatgaaa gtgtccgtcc 10680 gtgtgaggaa tcttggccca gataggaccc tgcaggtaca cgtcccggtc ctgccagacc 10740 atgccaggta aggctccttg actgttgacg gtccctgtag caggagcggt gttggccgat 10800 tgcaggttag tggccaccgt gccgtactct tctgtggcca ctgggttggt ggttttaatt 10860 tcttcctcgt tggttatcat aacgttgtca aggtccacgt tgctatttcc agctccctgt 10920 ttcccaaata ttaagactcc gctcatcgga aaaaatttgt cttcgtcgtc cttgtgggtt 10980 gccatagcgg gaccgggatt taccagagag tctctgccat tcagatgata cttggtggca 11040 ccggtccagg caaagttgct gttgttattt tgattggttg tcttggagac gcgttgctgc 11100 cggtagcagg gcccgggtag ccagtttttg gcctgattcg ccatgctact aggcccggcc 11160 tgagaaaatt gcaacgtccg atttcctgcg gtaccactcg tggtctgagt ccgagacagg 11220 tagtacaggt actggtcgat gagggggttc atcagccggt ccaggctttg gctgtgcgcg 11280 tagctgctgt gaaaaggcac gtcctcaaac gtgtagctga actgaaagtt gttgcccgtt 11340 ctcagcattt gagaaggaaa gtattccagg cagtagaagg aggaacggcc cacggcctga 11400 ctgccattgt tcagagtcag gtacccgtac tgaggaatca tgaagacgtc cgccgggaac 11460 ggaggcaggc agccctggtg cgcagagccg aggacgtacg ggagctggta ttccgagtcc 11520 gtaaagacct gaaccgtgct ggtaaggtta ttggcgatgg tcgtggtgcc atcattcgtc 11580 gtgacctcct tgacctggat gttgaagagc ttgaagttga gcttcttggg ccggaatccc 11640 cagttgttgt tgatgagtcg ctgccagtca cgtggtgaga agtggcagtg gaatctgtta 11700 aagtcaaaat acccccaggg ggtgctgtag ccgaagtagg tgttgtcgtt ggtgctgcct 11760 cccgattggc tggagatttg cttgtagagg tggttgttgt aggtggggag ggcccaggtt 11820 cgggtgctgg tggtgatgac tctgtcgccc agccatgtgg aatcgcaatg ccaatttcct 11880 gaggcgttac ccactccgtc ggcgccttcg ttattgtctg ccattggagc gccaccgcct 11940 gcagccattg tattagatcc cacaccagag ggggctgcgg ggggttctcc gagtggttga 12000 gggtcgggca ctgactctga gtcgccagtc tgcccaaagt tgagtctctt tctcgcgggc 12060 tgctggcctt tcttgccgat gcccgaagag gagtctggtt cctggggtga ttgctctacc 12120 ggtctcttct ttccaggagc cgtcttagcg ccttcctcaa ccagaccgag aggttcgaga 12180 acccgcttct tggcctggaa gactgctcgc ccgaggttgc ccccaaaaga cgtatcttct 12240 tgcagacgct cctgaaactc ggcgtcggcg tggttatacc gcaggtacgg attgtcaccc 12300 gctttgagct gctggtcgta ggccttgtcg tgctcgaggg ccgctgcgtc cgccgcgttg 12360 acgggctccc ccttgtcgag tccgttgaag ggtccgaggt acttgtagcc aggaagcacc 12420 agaccccggc cgtcgtcctg cttttgctgg ttggctttgg gtttcggggc tccaggtttc 12480 aagtcccacc actcgcgaat gccctcagag aggttgtcct cgagccaatc tggaagataa 12540 ccatcggcag ccatacctga tttaaatcat ttattgttca aagatgcagt catccaaatc 12600 cacattgacc agatcgcagg cagtgcaagc gtctggcacc tttcccatga tatgatgaat 12660 gtagcacagt ttctgatacg cctttttgac gacagaaacg ggttgagatt ctgacacggg 12720 aaagcactct aaacagtctt tctgtccgtg agtgaagcag atatttgaat tctgattcat 12780 tctctcgcat tgtctgcagg gaaacagcat cagattcatg cccacgtgac gagaacattt 12840 gttttggtac ctgtctgcgt agttgatcga agcttccgcg tctgacgtcg atggctgcgc 12900 aactgactcg cgcacccgtt tgggctcact tatatctgcg tcactggggg cgggtctttt 12960 cttggctcca ccctttttga cgtagaattc atgctccacc tcaaccacgt gatcctttgc 13020 ccaccggaaa aagtctttga cttcctgctt ggtgaccttc ccaaagtcat gatccagacg 13080 gcgggtgagt tcaaatttga acatccggtc ttgcaacggc tgctggtgtt cgaaggtcgt 13140 tgagttcccg tcaatcacgg cgcacatgtt ggtgttggag gtgacgatca cgggagtcgg 13200 gtctatctgg gccgaggact tgcatttctg gtccacgcgc accttgcttc ctccgagaat 13260 ggctttggcc gactccacga ccttggcggt catcttcccc tcctcccacc agatcaccat 13320 cttgtcgaca cagtcgttga agggaaagtt ctcattggtc cagtttacgc acccgtagaa 13380 gggcacagtg tgggctatgg cctccgcgat gttggtcttc ccggtagttg caggcccaaa 13440 cagccagatg gtgttcctct tgccgaactt tttcgtggcc catcccagaa agacggaagc 13500 cgcatattgg ggatcgtacc cgtttagttc caaaatttta taaatccgat tgctggaaat 13560 gtcctccacg ggctgctggc ccaccaggta gtcgggggcg gttttagtca ggctcataat 13620 ctttcccgca ttgtccaagg cagccttgat ttgggaccgc gagttggagg ccgcattgaa 13680 ggagatgtat gaggcctggt cctcctggat ccactgcttc tccgaggtaa tccccttgtc 13740 cacgagccac ccgaccagct ccatgtacct ggctgaagtt tttgatctga tcaccggcgc 13800 atcagaattg ggattctgat tctctttgtt ctgctcctgc gtctgcgaca cgtgcgtcag 13860 atgctgcgcc accaaccgtt tacgctccgt gagattcaaa caggcgctgt ggagagaaag 13920 gcaaagtgga tgtcagtatc tctatcactg atagggagat ctctatcact gatagggaac 13980 ttaccttaaa tactgttcca tattagtcca cgcccactgg agctcaggct gggttttggg 14040 gagcaagtaa ttggggatgt agcactcatc caccaccttg ttcccgcctc cggcgccatt 14100 tctggtcttt gtgaccgcga accagtttgg caaagtcggc tcgatcccgc ggtaaattct 14160 ctgaatcagt ttttcgcgaa tctgactcag gaaacgtccc aaaaccatgg atttcacccc 14220 ggtggtttcc acgagcacgt gcatgtggaa gtagctctct cccttctcaa attgcacaaa 14280 gaaaagagcc tccggggcct tactcacacg gcgccattcc gtcagaaagt cgcgctgcag 14340 cttctcggcc acggtcaggg gtgcctgctc aatcagattc agatccatgt cagaatctgg 14400 cggcaactcc cattccttct cggccaccca gttcacaaag ctgtcagaaa tgccgggcag 14460 atgctcgtca aggtcgctgg ggaccttaat cacaatctcg taaaaccccg gcatggcggc 14520 tgcgcgttca aacctcccgc ttcaaaatgg agaccctgcg tgctcactcg ggcgatctct 14580 atcactgata gggagatctc tatcactgat agggagatta aatagaatgg ctaggatccg 14640 gccggcctgc aggtgtcctc acaggaacga agtccctaaa gaaacagtgg cagccaggtt 14700 tagccccgga attgactgga ttcctttttt agggcccatt ggtatggctt tttccccgta 14760 tccccccagg tgtctgcagg ctcaaagagc agcgagaagc gttcagagga aagcgatccc 14820 gtgccacctt ccccgtgccc gggctgtccc cgcacgctgc cggctcgggg atgcgggggg 14880 agcgccggac cggagcggag ccccgggcgg ctcgctgctg ccccctagcg ggggagggac 14940 gtaattacat ccctgggggc tttggggggg ggctgtccct ctagagcggc cgccaccgcg 15000 gtggagctcc agcttttgtt ccctttagtg agggttaatt agatcttaat acgactcact 15060 atagggcgaa ttgggtaccg ggccccccct cgaggtcgac ggtatcgcct ccaaggccag 15120 cttcccacaa taagttgggt gaattttggc tcattcctcc tttctatagg attgaggtca 15180 gagctttgtg atgggaattc tgtggaatgt gtgtcagtta gggtgtggaa agtcccgcga 15240 tcgctagcaa acgccagcaa cgcggccttt ttacggttcc tggccttttg ctggcctttt 15300 gctcacatgt cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag 15360 cccgggcgtc gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag 15420 ggagtggcca actccatcac taggggttcc tgcggccgca cgcgtggagc tagttattaa 15480 tagtaatcaa ttacggggtc attagttcat agcccatata tggagttccg cgttacataa 15540 cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt gacgtcaata 15600 atgacgtatg ttcccatagt aacgtcaata gggactttcc attgacgtca atgggtggag 15660 tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc aagtacgccc 15720 cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta 15780 tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac catggtgatg 15840 cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg atttccaagt 15900 ctccacccca ttgacgtcaa tgggagtttg ttttgcacca aaatcaacgg gactttccaa 15960 aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg 16020 tctatataag cagagctcgt ttagtgaacc gtcagatcgc ctggagacgc catccacgct 16080 gttttgacct ccatagaaga caccgggacc gatccagcct ccgcggattc gaatcccggc 16140 cgggaacggt gcattggaac gcggattccc cgtgccaaga gtgacgtaag taccgcctat 16200 agagtctata ggcccacaaa aaatgctttc ttcttttaat atactttttt gtttatctta 16260 tttctaatac tttccctaat ctctttcttt cagggcaata atgatacaat gtatcatgcc 16320 tctttgcacc attctaaaga ataacagtga taatttctgg gttaaggcaa tagcaatatt 16380 tctgcatata aatatttctg catataaatt gtaactgatg taagaggttt catattgcta 16440 atagcagcta caatccagct accattctgc ttttatttta tggttgggat aaggctggat 16500 tattctgagt ccaagctagg cccttttgct aatcatgttc atacctctta tcttcctccc 16560 acagctcctg ggcaacgtgc tggtctgtgt gctggcccat cactttggca aagaattggg 16620 attcgaacat cgattgaatt ctgaatggtg agcaagggcg aggagctgtt caccggggtg 16680 gtgcccatcc tggtcgagct ggacggcgac gtaaacggcc acaagttcag cgtgtccggc 16740 gagggcgagg gcgatgccac ctacggcaag ctgaccctga agttcatctg caccaccggc 16800 aagctgcccg tgccctggcc caccctcgtg accaccctga cctacggcgt gcagtgcttc 16860 agccgctacc ccgaccacat gaagcagcac gacttcttca agtccgccat gcccgaaggc 16920 tacgtccagg agcgcaccat cttcttcaag gacgacggca actacaagac ccgcgccgag 16980 gtgaagttcg agggcgacac cctggtgaac cgcatcgagc tgaagggcat cgacttcaag 17040 gaggacggca acatcctggg gcacaagctg gagtacaact acaacagcca caacgtctat 17100 atcatggccg acaagcagaa gaacggcatc aaggtgaact tcaagatccg ccacaacatc 17160 gaggacggca gcgtgcagct cgccgaccac taccagcaga acacccccat cggcgacggc 17220 cccgtgctgc tgcccgacaa ccactacctg agcacccagt ccgccctgag caaagacccc 17280 aacgagaagc gcgatcacat ggtcctgctg gagttcgtga ccgccgccgg gatcactctc 17340 ggcatggacg agctgtacaa gtactcagat ctcgagctca agtagggatc ctctagagtc 17400 gacctgcaga agcttgcctc gagcagcgct gctcgagaga tctacgggtg gcatccctgt 17460 gacccctccc cagtgcctct cctggccctg gaagttgcca ctccagtgcc caccagcctt 17520 gtcctaataa aattaagttg catcattttg tctgactagg tgtccttcta taatattatg 17580 gggtggaggg gggtggtatg gagcaagggg caagttggga agacaacctg tagggcctgc 17640 ggggtctatt gggaaccaag ctggagtgca gtggcacaat cttggctcac tgcaatctcc 17700 gcctcctggg ttcaagcgat tctcctgcct cagcctcccg agttgttggg attccaggca 17760 tgcatgacca ggctcagcta atttttgttt ttttggtaga gacggggttt caccatattg 17820 gccaggctgg tctccaactc ctaatctcag gtgatctacc caccttggcc tcccaaattg 17880 ctgggattac aggcgtgaac cactgctccc ttccctgtcc ttctgatttt gtaggtaacc 17940 acgtgcggac cgagcggccg caggaacccc tagtgatgga gttggccact ccctctctgc 18000 gcgctcgctc gctcactgag gccgggcgac caaaggtcgc ccgacgcccg ggctttgccc 18060 gggcggcctc agtgagcgag cgagcgcgca gctgcctgca ggggcgcctg atgcggtatt 18120 ttctccttac gcatctgtgc ggtatttcac accgcatacg tcgtagctga tcaattggcg 18180 cgccgaattc gttaacaagc tttaattaac gcgtacgata agcttgatat ctataacaag 18240 aaaatatata tataataagt tatcacgtaa gtagaacatg aaataacaat ataattatcg 18300 tatgagttaa atcttaaaag tcacgtaaaa gataatcatg cgtcattttg actcacgcgg 18360 tcgttatagt tcaaaatcag tgacacttac cgcattgaca agcacgcctc acgggagctc 18420 caagcggcga ctgagatgtc ctaaatgcac agcgacggat tcgcgctatt tagaaagaga 18480 gagcaatatt tcaagaatgc atgcgtcaat tttacgcaga ctatctttct agggttaatc 18540 tagctgcatc aggatcatat cgtcgggtct tttttccggc tcagtcatcg cccaagctgg 18600 cgctatctgg gcatcgggga ggaagaagcc cgtgcctttt cccgcgaggt tgaagcggca 18660 tggaaagagt ttgccgagga tgactgctgc tgcattgacg ttgagcgaaa acgcacgttt 18720 accatgatga ttcgggaagg tgtggccatg cacgccttta acggtgaact gttcgttcag 18780 gccacctggg ataccagttc gtcgcggctt ttccggacac agttccggat ggtcagcccg 18840 aagcgcatca gcaacccgaa caataccggc gacagccgga actgccgtgc cggtgtgcag 18900 attaatgaca gcggtgcggc gctgggatat tacgtcagcg aggacgggta tcctggctgg 18960 atgccgcaga aatggacatg gataccccgt gagttacccg gcgggcgcgc ttggcgtaat 19020 catggtcata gctgtttcct gtgtgaaatt gttatccgct cacaattcca cacaacatac 19080 gagccggaag cataaagtgt aaagcctggg gtgcctaatg agtgagctaa ctcacattaa 19140 ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat 19200 gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc 19260 tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg 19320 cggtaatacg gttatccaca gaatcagggg ataacgcagg aaagaacatg tgagcaaaag 19380 gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc 19440 gcccccctga cgagcatcac aaaaatcgac gctcaagtca gaggtggcga aacccgacag 19500 gactataaag ataccaggcg tttccccctg gaagctccct cgtgcgctct cctgttccga 19560 ccctgccgct taccggatac ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc 19620 atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg 19680 tgcacgaacc ccccgttcag cccgaccgct gcgccttatc cggtaactat cgtcttgagt 19740 ccaacccggt aagacacgac ttatcgccac tggcagcagc cactggtaac aggattagca 19800 gagcgaggta tgtaggcggt gctacagagt tcttgaagtg gtggcctaac tacggctaca 19860 ctagaaggac agtatttggt atctgcgctc tgctgaagcc agttaccttc ggaaaaagag 19920 ttggtagctc ttgatccggc aaacaaacca ccgctggtag cggtggtttt tttgtttgca 19980 agcagcagat tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg 20040 ggtctgacgc tcagtggaac gaaaactcac gttaagggat tttggtcatg agattatcaa 20100 aaaggatctt cacctagatc cttttaaatt aaaaatgaag ttttaaatca atctaaagta 20160 tatatgagta aacttggtct gacagttacc aatgcttaat cagtgaggca cctatctcag 20220 cgatctgtct atttcgttca tccatagttg cctgactccc cgtcgtgtag ataactacga 20280 tacgggaggg cttaccatct ggccccagtg ctgcaatgat accgcgagac ccacgctcac 20340 cggctccaga tttatcagca ataaaccagc cagccggaag ggccgagcgc agaagtggtc 20400 ctgcaacttt atccgcctcc atccagtcta ttaattgttg ccgggaagct agagtaagta 20460 gttcgccagt taatagtttg cgcaacgttg ttgccattgc tacaggcatc gtggtgtcac 20520 gctcgtcgtt tggtatggct tcattcagct ccggttccca acgatcaagg cgagttacat 20580 gatcccccat gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc gttgtcagaa 20640 gtaagttggc cgcagtgtta tcactcatgg ttatggcagc actgcataat tctcttactg 20700 tcatgccatc cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag tcattctgag 20760 aatagtgtat gcggcgaccg agttgctctt gcccggcgtc aatacgggat aataccgcgc 20820 cacatagcag aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg cgaaaactct 20880 caaggatctt accgctgttg agatccagtt cgatgtaacc cactcgtgca cccaactgat 20940 cttcagcatc ttttactttc accagcgttt ctgggtgagc aaaaacagga aggcaaaatg 21000 ccgcaaaaaa gggaataagg gcgacacgga aatgttgaat actcat 21046 <210> 15 <211> 10497 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 15 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatct ccctatcagt 60 gatagagatc gcccgagtga gcacgcaggg tctccatttt gaagcgggag gtttgaacgc 120 gcagccgcca tgccggggtt ttacgagatt gtgattaagg tccccagcga ccttgacgag 180 catctgcccg gcatttctga cagctttgtg aactgggtgg ccgagaagga atgggagttg 240 ccgccagatt ctgacatgga tctgaatctg attgagcagg cacccctgac cgtggccgag 300 aagctgcagc gcgactttct gacggaatgg cgccgtgtga gtaaggcccc ggaggctctt 360 ttctttgtgc aatttgagaa gggagagagc tacttccaca tgcacgtgct cgtggaaacc 420 accggggtga aatccatggt tttgggacgt ttcctgagtc agattcgcga aaaactgatt 480 cagagaattt accgcgggat cgagccgact ttgccaaact ggttcgcggt cacaaagacc 540 agaaatggcg ccggaggcgg gaacaaggtg gtggatgagt gctacatccc caattacttg 600 ctccccaaaa cccagcctga gctccaatgg gcatggacca acatggaaca gtacctcagc 660 gcctgtttga atctcacgga gcgtaaacgg ttggtggcgc agcatctgac gcacgtgtcg 720 cagacgcagg agcagaacaa agagaatcag aatcccaatt ctgatgcgcc ggtgatcaga 780 tcaaaaactt cagccaggta catggagctg gtcgggtggc tcgtggacaa ggggattacc 840 tcggagaagc agtggatcca ggaggaccag gcctcataca tctccttcaa tgcggcctcc 900 aactcgcggt cccaaatcaa ggctgccttg gacaatgcgg gaaagattat gagcctgact 960 aaaaccgccc ccgactacct ggtgggccag cagcccgtgg aggacatttc cagcaatcgg 1020 atttataaaa ttttggaact aaacgggtac gatccccaat atgcggcttc cgtctttctg 1080 ggatgggcca cgaaaaagtt cggcaagagg aacaccatct ggctgtttgg gcctgcaact 1140 accgggaaga ccaacatcgc ggaggccata gcccacactg tgcccttcta cgggtgcgta 1200 aactggacca atgagaactt tcccttcaac gactgtgtcg acaagatggt gatctggtgg 1260 gaggagggga agatgaccgc caaggtcgtg gagtcggcca aagccattct cggaggaagc 1320 aaggtgcgcg tggaccagaa atgcaagtcc tcggcccaga tagacccgac tcccgtgatc 1380 gtcacctcca acaccaacat gtgcgccgtg attgacggga actcaacgac cttcgaacac 1440 cagcagccgt tgcaagaccg gatgttcaaa tttgaactca cccgccgtct ggatcatgac 1500 tttgggaagg tcaccaagca ggaagtcaaa gactttttcc ggtgggcaaa ggatcacgtg 1560 gttgaggtgg agcatgaatt ctacgtcaaa aagggtggag ccaagaaaag acccgccccc 1620 agtgacgcag atataagtga gcccaaacgg gtgcgcgagt cagttgcgca gccatcgacg 1680 tcagacgcgg aagcttcgat caactacgca gacaggtacc aaaacaaatg ttctcgtcac 1740 gtgggcatga atctgatgct gtttccctgc agacaatgcg agagaatgaa tcagaattca 1800 aatatctgct tcactcacgg acagaaagac tgtttagagt gctttcccgt gtcagaatct 1860 caacccgttt ctgtcgtcaa aaaggcgtat cagaaactgt gctacattca tcatatcatg 1920 ggaaaggtgc cagacgcttg cactgcctgc gatctggtca atgtggattt ggatgactgc 1980 atctttgaac aataaatgat ttaaatcagg tatggctgcc gatggttatc ttccagattg 2040 gctcgaggac aacctctctg agggcattcg cgagtggtgg gacttgaaac ctggagcccc 2100 gaaacccaaa gccaaccagc aaaagcagga cgacggccgg ggtctggtgc ttcctggcta 2160 caagtacctc ggacccttca acggactcga caagggggag cccgtcaacg cggcggacgc 2220 agcggccctc gagcacgaca aggcctacga ccagcagctc aaagcgggtg acaatccgta 2280 cctgcggtat aaccacgccg acgccgagtt tcaggagcgt ctgcaagaag atacgtcttt 2340 tgggggcaac ctcgggcgag cagtcttcca ggccaagaag cgggttctcg aacctctcgg 2400 tctggttgag gaaggcgcta agacggctcc tggaaagaag agaccggtag agcaatcacc 2460 ccaggaacca gactcctctt cgggcatcgg caagaaaggc cagcagcccg cgagaaagag 2520 actcaacttt gggcagactg gcgactcaga gtcagtgccc gaccctcaac cactcggaga 2580 accccccgca gccccctctg gtgtgggatc taatacaatg gctgcaggcg gtggcgctcc 2640 aatggcagac aataacgaag gcgccgacgg agtgggtaac gcctcaggaa attggcattg 2700 cgattccaca tggctgggcg acagagtcat caccaccagc acccgaacct gggccctccc 2760 cacctacaac aaccacctct acaagcaaat ctccagccaa tcgggaggca gcaccaacga 2820 caacacctac ttcggctaca gcaccccctg ggggtatttt gactttaaca gattccactg 2880 ccacttctca ccacgtgact ggcagcgact catcaacaac aactggggat tccggcccaa 2940 gaagctcaac ttcaagctct tcaacatcca ggtcaaggag gtcacgacga atgatggcac 3000 cacgaccatc gccaataacc ttaccagcac ggttcaggtc tttacggact cggaatacca 3060 gctcccgtac gtcctcggct ctgcgcacca gggctgcctg cctccgttcc cggcggacgt 3120 cttcatgatt cctcagtacg ggtacctgac tctgaacaat ggcagtcagg ccgtgggccg 3180 ttcctccttc tactgcctgg aatactttcc ttctcaaatg ctgagaacgg gcaacaactt 3240 tcagttcagc tacacgtttg aggacgtgcc ttttcacagc agctacgcgc acagccaaag 3300 cctggaccgg ctgatgaacc ccctcatcga ccagtacctg tactacctgt ctcggactca 3360 gaccacgagt ggtaccgcag gaaatcggac gttgcaattt tctcaggccg ggcctagtag 3420 catggcgaat caggccaaaa actggctacc cgggccctgc taccggcagc aacgcgtctc 3480 caagacaacc aatcaaaata acaacagcaa ctttgcctgg accggtgcca ccaagtatca 3540 tctgaatggc agagactctc tggtaaatcc cggtcccgct atggcaaccc acaaggacga 3600 cgaagacaaa ttttttccga tgagcggagt cttaatattt gggaaacagg gagctggaaa 3660 tagcaacgtg gaccttgaca acgttatgat aaccaacgag gaagaaatta aaaccaccaa 3720 cccagtggcc acagaagagt acggcacggt ggccactaac ctgcaatcgg ccaacaccgc 3780 tcctgctaca gggaccgtca acagtcaagg agccttacct ggcatggtct ggcaggaccg 3840 ggacgtgtac ctgcagggtc ctatctgggc caagattcct cacacggacg gacactttca 3900 tccctcgccg ctgatgggag gctttggact gaaacacccg cctcctcaga tcctgattaa 3960 gaatacacct gttcccgcga atcctccaac taccttcagt ccagctaagt ttgcgtcgtt 4020 catcacgcag tacagcaccg gacaggtcag cgtggaaatt gaatgggagc tgcagaaaga 4080 aaacagcaaa cgctggaacc cagagattca atacacttcc aactacaaca aatctacaaa 4140 tgtggacttt gctgttgaca caaatggcgt ttattctgag cctcgcccca tcggcacccg 4200 ttacctcacc cgtaatctgt aaactagttt gcttgttaat caataaaccg tttaattcgt 4260 ttcagttgaa ctttggtctc tgcgtatttc tttcttatct agtttccatg ctctagaggt 4320 cctgtattag aggtcacgtg agtgttttgc gacattttgc gacaccatgt ggtcacgctg 4380 ggtatttaag cccgagtgag cacgcagggt ctccattttg aagcgggagg tttgaacgcg 4440 cagccgccaa gccgaattct gcagatatcg gggttggggt tgcgcctttt ccaaggcagc 4500 cctgggtttg cgcagggacg cggctgctct gggcgtggtt ccgggaaacg cagcggcgcc 4560 gaccctgggt ctcgcacatt cttcacgtcc gttcgcagcg tcacccggat cttcgccgct 4620 acccttgtgg gccccccggc gacgcttcct gctccgcccc taagtcggga aggttccttg 4680 cggttcgcgg cgtgccggac gtgacaaacg gaagccgcac gtctcactag taccctcgca 4740 gacggacagc gccagggagc aatggcagcg cgccgaccgc gatgggctgt ggccaatagc 4800 ggctgctcag cagggcgcgc cgagagcagc ggccgggaag gggcggtgcg ggaggcgggg 4860 tgtggggcgg tagtgtgggc cctgttcctg cccgcgcggt gttccgcatt ctgcaagcct 4920 ccggagcgca cgtcggcagt cggctccctc gttgaccgaa tcaccgacct ctctccccag 4980 aagctcccgg gagcttgtat atccattttc ggatctgatc agcacgtgtt gacaattaat 5040 catcggcata gtatatcggc atagtataat acgacaaggt gaggaacgcc accatggcca 5100 agcctttgtc tcaagaagaa tccaccctca ttgaaagagc aacggctaca atcaacagca 5160 tccccatctc tgaagactac agcgtcgcca gcgcagctct ctctagcgac ggccgcatct 5220 tcactggtgt caatgtatat cattttactg ggggaccttg tgcagaactc gtggtgctgg 5280 gcactgctgc tgctgcggca gctggcaacc tgacttgtat cgtcgcgatc ggaaatgaga 5340 acaggggcat cttgagcccc tgcggacggt gccgacaggt gcttctcgat ctgcatcctg 5400 ggatcaaagc catagtgaag gacagtgatg gacagccgac ggcagttggg attcgtgaat 5460 tgctgccctc tggttatgtg tgggagggct aagcacttcg tggccgagga gcaggactga 5520 cacgtgctac gagatttcga ttccaccgcc gccttctatg aaaggttggg cttcggaatc 5580 gttttccggg acgccggctg gatgatcctc cagcgcgggg atctcatgct ggagttcttc 5640 gcccacccca acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 5700 aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 5760 aatgtatctt agcgctcact gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat 5820 taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc tcctaggcca 5880 gaaatggcgc cggaggcggg aacaaggtgg tggatgagtg ctacatcccc aattacttgc 5940 tccccaaaac ccagcctgag ctccagtggg cgtggactaa tatggaacag tatttaagcg 6000 cctgtcccta tcagtgatag agatctccct atcagtgata gagatttgaa tctcacggag 6060 cgtaaacggt tggtggcgca gcatctgttt aaacgcagac gcaggagcag aacaaagaga 6120 atcagaatcc caattctgat gcgccggtga tcagatcaaa aacttcagcc aggtacatgg 6180 agctggtcgg gtggctcgtg gacaagggga ttacctcgga gaagcagtgg attcaggagg 6240 accaggcctc atacatctcc ttcaatgcgg cctccaactc gcggtcccaa atcaaggctg 6300 ccttggacaa tgcgggaaag attatgagcc tgactaaaac cgcccccgac tacctggtgg 6360 gccagcagcc cgtggaggac atttccagca atcggattta taaaattttg gaactaaacg 6420 ggtacgatcc ccaatatgcg gcttccgtct ttctgggatg ggccacgaaa aagttcggca 6480 agaggaacac catctggctg tttgggcctg caactaccgg gaagaccaac atcgcggagg 6540 ccatagccca cactgtgccc ttctacgggt gcgtaaactg gaccaatgag aactttccct 6600 tcaacgactg tgtcgacaag atggtgatct ggtgggagga ggggaagatg accgccaagg 6660 tcgtggagtc ggccaaagcc attctcggag gaagcaaggt gcgcgtggac cagaaatgca 6720 agtcctcggc ccagatagac ccgactcccg tgatcgtcac ctccaacacc aacatgtgcg 6780 ccgtgattga cgggaactca acgaccttcg aacaccagca gccgttgcaa gaccggatgt 6840 tcaaatttga actcacccgc cgtctggatc atgactttgg gaaggtcacc aagcaggaag 6900 tcaaagactt tttccggtgg gcaaaggatc acgtggttga ggtggagcat gaattctacg 6960 tcaaaaaggg tggagccaag aaaagacccg cccccagtga cgcagatata agtgagccca 7020 aacgggtgcg cgagtcagtt gcgcagccat cgacgtcaga cgcggaagct tcgatcaact 7080 acgcagacag gtaccaaaac aaatgttctc gtcacgtggg catgaatctg atgctgtttc 7140 cctgcagaca atgcgagaga atgaatcaga attcaaatat ctgcttcact cacggacaga 7200 aagactgttt agagtgcttt cccgtgtcag aatctcaacc cgtttctgtc gtcaaaaagg 7260 cgtatcagaa actgtgctac attcatcata tcatgggaaa ggtgccagac gcttgcactg 7320 cctgcgatct ggtcaatgtg gatttggatg actgcatctt tgaacaataa actagtttgc 7380 ttgttaatca ataaaccgtt taattcgttt cagttgaact ttggtctctg cgtatttctt 7440 tcttatctag tttccatgct ctagagtata cgatatccat cacactggcg gccgctcgac 7500 tagagcggcc gccaccgcgg tggagctcca gcttttgttc gcgcgcttgg cgtaatcatg 7560 gtcatagctg tttcctgtgt gaaattccac agcctggggt gcctaattgc gttgcgctca 7620 ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc 7680 gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac tgactcgctg 7740 cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta 7800 tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc 7860 aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc ccctgacgag 7920 catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact ataaagatac 7980 caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct gccgcttacc 8040 ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcatag ctcacgctgt 8100 aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc 8160 gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa cccggtaaga 8220 cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc gaggtatgta 8280 ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag aagaacagta 8340 tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg tagctcttga 8400 tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca gcagattacg 8460 cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc tgacgctcag 8520 tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag gatcttcacc 8580 tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata tgagtaaact 8640 tggtctgaca gaaataataa aaaagccgga ttaataatct ggctttttat attctctctc 8700 tagtatataa acgcagaaag gcccacccga aggtgagcca gtgtgactct agtattatta 8760 gaaaaactca tcgagcatca aatgaaactg caatttattc atatcaggat tatcaatacc 8820 atatttttga aaaagccgtt tctgtaatga aggagaaaac tcaccgaggc agttccaaag 8880 aatggcaagg tcctggtaac ggtctgcgat tccgacccgt ccaacatcaa tacaacctat 8940 taatttcccc tcgtcaaaaa taaggttatc aagtgagaaa tcaccatgag tgacgactga 9000 atccggtgag aatggcaaga gcttgtgcat ttctttccag acttgttcaa caggccagcc 9060 attacgctcg tcatcaaaat cactcgcatc aaccaaaccg ttattcatgc gtgattgcgc 9120 ctgagcaaga cgaaatacac gatcgctgtt aaaaggacaa ttacaaacag gaatcgaatg 9180 taaccggcgc aggaacacgg ccagcgcatc aacaatattt tcacctgaat caggatattc 9240 ttctaatacc tggaaggctg ttttcccagg aatcgcggtg gtgagtaacc acgcatcatc 9300 aggagtacgg ataaaatgct tgatggtcgg gagaggcata aactccgtca gccagttgag 9360 acggaccatc tcatctgtaa catcattggc aacgctacct ttgccatgtt tcagaaacaa 9420 ctctggcgca tcgggcttcc catacaagcg atagattgtc gcacctgatt gcccgacatt 9480 atcgcgagcc catttatacc catataaatc agcgtccatg ttggagttta agcgcggacg 9540 ggagcaagac gtttcccgtt gaatatggct cataacaccc cttgtattac tgtttatgta 9600 agcagacagt tttattgttc atgatgatat atttttatct tgtgcaatgt aacatcagag 9660 attttgagac acaacgtggc tttgttgaat aaatcgaact tttgctgagt tgaaggatca 9720 gctctagtaa aataataaaa aagccggatt aataatctgg ctttttatat tctctctcta 9780 gtatataaac gcagaaaggc ccacccgaag gtgagccagt gtgacggcac atttccccga 9840 aaagtgccac ctaaattgta agcgttaata ttttgttaaa attcgcgtta aatttttgtt 9900 aaatcagctc attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag 9960 aatagaccga gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga 10020 acgtggactc caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg 10080 aaccatcacc ctaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc 10140 ctaaagggag cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg 10200 aagggaagaa agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc 10260 gcgtaaccac cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc cattcgccat 10320 tcaggctgcg caactgttgg gaagggcgat cggtgcgggc ctcttcgcta ttacgccagc 10380 tggcgaaagg gggatgtgct gcaaggcgat taagttgggt aacgccaggg ttttcccagt 10440 cacgacgttg taaaacgacg gccagtgagc gcgcggcgaa ttgggtaccg ggccccc 10497 <210> 16 <211> 10495 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 16 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatcg cccgagtgag 60 cacgcagggt ctccattttg atccctatca gtgatagaga agcgggaggt ttgaacgcgc 120 agccgccatg ccggggtttt acgagattgt gattaaggtc cccagcgacc ttgacgagca 180 tctgcccggc atttctgaca gctttgtgaa ctgggtggcc gagaaggaat gggagttgcc 240 gccagattct gacatggatc tgaatctgat tgagcaggca cccctgaccg tggccgagaa 300 gctgcagcgc gactttctga cggaatggcg ccgtgtgagt aaggccccgg aggctctttt 360 ctttgtgcaa tttgagaagg gagagagcta cttccacatg cacgtgctcg tggaaaccac 420 cggggtgaaa tccatggttt tgggacgttt cctgagtcag attcgcgaaa aactgattca 480 gagaatttac cgcgggatcg agccgacttt gccaaactgg ttcgcggtca caaagaccag 540 aaatggcgcc ggaggcggga acaaggtggt ggatgagtgc tacatcccca attacttgct 600 ccccaaaacc cagcctgagc tccaatgggc atggaccaac atggaacagt acctcagcgc 660 ctgtttgaat ctcacggagc gtaaacggtt ggtggcgcag catctgacgc acgtgtcgca 720 gacgcaggag cagaacaaag agaatcagaa tcccaattct gatgcgccgg tgatcagatc 780 aaaaacttca gccaggtaca tggagctggt cgggtggctc gtggacaagg ggattacctc 840 ggagaagcag tggatccagg aggaccaggc ctcatacatc tccttcaatg cggcctccaa 900 ctcgcggtcc caaatcaagg ctgccttgga caatgcggga aagattatga gcctgactaa 960 aaccgccccc gactacctgg tgggccagca gcccgtggag gacatttcca gcaatcggat 1020 ttataaaatt ttggaactaa acgggtacga tccccaatat gcggcttccg tctttctggg 1080 atgggccacg aaaaagttcg gcaagaggaa caccatctgg ctgtttgggc ctgcaactac 1140 cgggaagacc aacatcgcgg aggccatagc ccacactgtg cccttctacg ggtgcgtaaa 1200 ctggaccaat gagaactttc ccttcaacga ctgtgtcgac aagatggtga tctggtggga 1260 ggaggggaag atgaccgcca aggtcgtgga gtcggccaaa gccattctcg gaggaagcaa 1320 ggtgcgcgtg gaccagaaat gcaagtcctc ggcccagata gacccgactc ccgtgatcgt 1380 cacctccaac accaacatgt gcgccgtgat tgacgggaac tcaacgacct tcgaacacca 1440 gcagccgttg caagaccgga tgttcaaatt tgaactcacc cgccgtctgg atcatgactt 1500 tgggaaggtc accaagcagg aagtcaaaga ctttttccgg tgggcaaagg atcacgtggt 1560 tgaggtggag catgaattct acgtcaaaaa gggtggagcc aagaaaagac ccgcccccag 1620 tgacgcagat ataagtgagc ccaaacgggt gcgcgagtca gttgcgcagc catcgacgtc 1680 agacgcggaa gcttcgatca actacgcaga caggtaccaa aacaaatgtt ctcgtcacgt 1740 gggcatgaat ctgatgctgt ttccctgcag acaatgcgag agaatgaatc agaattcaaa 1800 tatctgcttc actcacggac agaaagactg tttagagtgc tttcccgtgt cagaatctca 1860 acccgtttct gtcgtcaaaa aggcgtatca gaaactgtgc tacattcatc atatcatggg 1920 aaaggtgcca gacgcttgca ctgcctgcga tctggtcaat gtggatttgg atgactgcat 1980 ctttgaacaa taaatgattt aaatcaggta tggctgccga tggttatctt ccagattggc 2040 tcgaggacaa cctctctgag ggcattcgcg agtggtggga cttgaaacct ggagccccga 2100 aacccaaagc caaccagcaa aagcaggacg acggccgggg tctggtgctt cctggctaca 2160 agtacctcgg acccttcaac ggactcgaca agggggagcc cgtcaacgcg gcggacgcag 2220 cggccctcga gcacgacaag gcctacgacc agcagctcaa agcgggtgac aatccgtacc 2280 tgcggtataa ccacgccgac gccgagtttc aggagcgtct gcaagaagat acgtcttttg 2340 ggggcaacct cgggcgagca gtcttccagg ccaagaagcg ggttctcgaa cctctcggtc 2400 tggttgagga aggcgctaag acggctcctg gaaagaagag accggtagag caatcacccc 2460 aggaaccaga ctcctcttcg ggcatcggca agaaaggcca gcagcccgcg agaaagagac 2520 tcaactttgg gcagactggc gactcagagt cagtgcccga ccctcaacca ctcggagaac 2580 cccccgcagc cccctctggt gtgggatcta atacaatggc tgcaggcggt ggcgctccaa 2640 tggcagacaa taacgaaggc gccgacggag tgggtaacgc ctcaggaaat tggcattgcg 2700 attccacatg gctgggcgac agagtcatca ccaccagcac ccgaacctgg gccctcccca 2760 cctacaacaa ccacctctac aagcaaatct ccagccaatc gggaggcagc accaacgaca 2820 acacctactt cggctacagc accccctggg ggtattttga ctttaacaga ttccactgcc 2880 acttctcacc acgtgactgg cagcgactca tcaacaacaa ctggggattc cggcccaaga 2940 agctcaactt caagctcttc aacatccagg tcaaggaggt cacgacgaat gatggcacca 3000 cgaccatcgc caataacctt accagcacgg ttcaggtctt tacggactcg gaataccagc 3060 tcccgtacgt cctcggctct gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct 3120 tcatgattcc tcagtacggg tacctgactc tgaacaatgg cagtcaggcc gtgggccgtt 3180 cctccttcta ctgcctggaa tactttcctt ctcaaatgct gagaacgggc aacaactttc 3240 agttcagcta cacgtttgag gacgtgcctt ttcacagcag ctacgcgcac agccaaagcc 3300 tggaccggct gatgaacccc ctcatcgacc agtacctgta ctacctgtct cggactcaga 3360 ccacgagtgg taccgcagga aatcggacgt tgcaattttc tcaggccggg cctagtagca 3420 tggcgaatca ggccaaaaac tggctacccg ggccctgcta ccggcagcaa cgcgtctcca 3480 agacaaccaa tcaaaataac aacagcaact ttgcctggac cggtgccacc aagtatcatc 3540 tgaatggcag agactctctg gtaaatcccg gtcccgctat ggcaacccac aaggacgacg 3600 aagacaaatt ttttccgatg agcggagtct taatatttgg gaaacaggga gctggaaata 3660 gcaacgtgga ccttgacaac gttatgataa ccaacgagga agaaattaaa accaccaacc 3720 cagtggccac agaagagtac ggcacggtgg ccactaacct gcaatcggcc aacaccgctc 3780 ctgctacagg gaccgtcaac agtcaaggag ccttacctgg catggtctgg caggaccggg 3840 acgtgtacct gcagggtcct atctgggcca agattcctca cacggacgga cactttcatc 3900 cctcgccgct gatgggaggc tttggactga aacacccgcc tcctcagatc ctgattaaga 3960 atacacctgt tcccgcgaat cctccaacta ccttcagtcc agctaagttt gcgtcgttca 4020 tcacgcagta cagcaccgga caggtcagcg tggaaattga atgggagctg cagaaagaaa 4080 acagcaaacg ctggaaccca gagattcaat acacttccaa ctacaacaaa tctacaaatg 4140 tggactttgc tgttgacaca aatggcgttt attctgagcc tcgccccatc ggcacccgtt 4200 acctcacccg taatctgtaa actagtttgc ttgttaatca ataaaccgtt taattcgttt 4260 cagttgaact ttggtctctg cgtatttctt tcttatctag tttccatgct ctagaggtcc 4320 tgtattagag gtcacgtgag tgttttgcga cattttgcga caccatgtgg tcacgctggg 4380 tatttaagcc cgagtgagca cgcagggtct ccattttgaa gcgggaggtt tgaacgcgca 4440 gccgccaagc cgaattctgc agatatcggg gttggggttg cgccttttcc aaggcagccc 4500 tgggtttgcg cagggacgcg gctgctctgg gcgtggttcc gggaaacgca gcggcgccga 4560 ccctgggtct cgcacattct tcacgtccgt tcgcagcgtc acccggatct tcgccgctac 4620 ccttgtgggc cccccggcga cgcttcctgc tccgccccta agtcgggaag gttccttgcg 4680 gttcgcggcg tgccggacgt gacaaacgga agccgcacgt ctcactagta ccctcgcaga 4740 cggacagcgc cagggagcaa tggcagcgcg ccgaccgcga tgggctgtgg ccaatagcgg 4800 ctgctcagca gggcgcgccg agagcagcgg ccgggaaggg gcggtgcggg aggcggggtg 4860 tggggcggta gtgtgggccc tgttcctgcc cgcgcggtgt tccgcattct gcaagcctcc 4920 ggagcgcacg tcggcagtcg gctccctcgt tgaccgaatc accgacctct ctccccagaa 4980 gctcccggga gcttgtatat ccattttcgg atctgatcag cacgtgttga caattaatca 5040 tcggcatagt atatcggcat agtataatac gacaaggtga ggaacgccac catggccaag 5100 cctttgtctc aagaagaatc caccctcatt gaaagagcaa cggctacaat caacagcatc 5160 cccatctctg aagactacag cgtcgccagc gcagctctct ctagcgacgg ccgcatcttc 5220 actggtgtca atgtatatca ttttactggg ggaccttgtg cagaactcgt ggtgctgggc 5280 actgctgctg ctgcggcagc tggcaacctg acttgtatcg tcgcgatcgg aaatgagaac 5340 aggggcatct tgagcccctg cggacggtgc cgacaggtgc ttctcgatct gcatcctggg 5400 atcaaagcca tagtgaagga cagtgatgga cagccgacgg cagttgggat tcgtgaattg 5460 ctgccctctg gttatgtgtg ggagggctaa gcacttcgtg gccgaggagc aggactgaca 5520 cgtgctacga gatttcgatt ccaccgccgc cttctatgaa aggttgggct tcggaatcgt 5580 tttccgggac gccggctgga tgatcctcca gcgcggggat ctcatgctgg agttcttcgc 5640 ccaccccaac ttgtttattg cagcttataa tggttacaaa taaagcaata gcatcacaaa 5700 tttcacaaat aaagcatttt tttcactgca ttctagttgt ggtttgtcca aactcatcaa 5760 tgtatcttag cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta 5820 atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctc ctaggccaga 5880 aatggcgccg gaggcgggaa caaggtggtg gatgagtgct acatccccaa ttacttgctc 5940 cccaaaaccc agcctgagct ccagtgggcg tggactaata tggaacagta tttaagcgcc 6000 tgtccctatc agtgatagag atctccctat cagtgataga gatttgaatc tcacggagcg 6060 taaacggttg gtggcgcagc atctgtttaa acgcagacgc aggagcagaa caaagagaat 6120 cagaatccca attctgatgc gccggtgatc agatcaaaaa cttcagccag gtacatggag 6180 ctggtcgggt ggctcgtgga caaggggatt acctcggaga agcagtggat tcaggaggac 6240 caggcctcat acatctcctt caatgcggcc tccaactcgc ggtcccaaat caaggctgcc 6300 ttggacaatg cgggaaagat tatgagcctg actaaaaccg cccccgacta cctggtgggc 6360 cagcagcccg tggaggacat ttccagcaat cggatttata aaattttgga actaaacggg 6420 tacgatcccc aatatgcggc ttccgtcttt ctgggatggg ccacgaaaaa gttcggcaag 6480 aggaacacca tctggctgtt tgggcctgca actaccggga agaccaacat cgcggaggcc 6540 atagcccaca ctgtgccctt ctacgggtgc gtaaactgga ccaatgagaa ctttcccttc 6600 aacgactgtg tcgacaagat ggtgatctgg tgggaggagg ggaagatgac cgccaaggtc 6660 gtggagtcgg ccaaagccat tctcggagga agcaaggtgc gcgtggacca gaaatgcaag 6720 tcctcggccc agatagaccc gactcccgtg atcgtcacct ccaacaccaa catgtgcgcc 6780 gtgattgacg ggaactcaac gaccttcgaa caccagcagc cgttgcaaga ccggatgttc 6840 aaatttgaac tcacccgccg tctggatcat gactttggga aggtcaccaa gcaggaagtc 6900 aaagactttt tccggtgggc aaaggatcac gtggttgagg tggagcatga attctacgtc 6960 aaaaagggtg gagccaagaa aagacccgcc cccagtgacg cagatataag tgagcccaaa 7020 cgggtgcgcg agtcagttgc gcagccatcg acgtcagacg cggaagcttc gatcaactac 7080 gcagacaggt accaaaacaa atgttctcgt cacgtgggca tgaatctgat gctgtttccc 7140 tgcagacaat gcgagagaat gaatcagaat tcaaatatct gcttcactca cggacagaaa 7200 gactgtttag agtgctttcc cgtgtcagaa tctcaacccg tttctgtcgt caaaaaggcg 7260 tatcagaaac tgtgctacat tcatcatatc atgggaaagg tgccagacgc ttgcactgcc 7320 tgcgatctgg tcaatgtgga tttggatgac tgcatctttg aacaataaac tagtttgctt 7380 gttaatcaat aaaccgttta attcgtttca gttgaacttt ggtctctgcg tatttctttc 7440 ttatctagtt tccatgctct agagtatacg atatccatca cactggcggc cgctcgacta 7500 gagcggccgc caccgcggtg gagctccagc ttttgttcgc gcgcttggcg taatcatggt 7560 catagctgtt tcctgtgtga aattccacag cctggggtgc ctaattgcgt tgcgctcact 7620 gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc 7680 ggggagaggc ggtttgcgta ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg 7740 ctcggtcgtt cggctgcggc gagcggtatc agctcactca aaggcggtaa tacggttatc 7800 cacagaatca ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag 7860 gaaccgtaaa aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca 7920 tcacaaaaat cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca 7980 ggcgtttccc cctggaagct ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg 8040 atacctgtcc gcctttctcc cttcgggaag cgtggcgctt tctcatagct cacgctgtag 8100 gtatctcagt tcggtgtagg tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt 8160 tcagcccgac cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc cggtaagaca 8220 cgacttatcg ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg 8280 cggtgctaca gagttcttga agtggtggcc taactacggc tacactagaa gaacagtatt 8340 tggtatctgc gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc 8400 cggcaaacaa accaccgctg gtagcggtgg tttttttgtt tgcaagcagc agattacgcg 8460 cagaaaaaaa ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg 8520 gaacgaaaac tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta 8580 gatcctttta aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg 8640 gtctgacaga aataataaaa aagccggatt aataatctgg ctttttatat tctctctcta 8700 gtatataaac gcagaaaggc ccacccgaag gtgagccagt gtgactctag tattattaga 8760 aaaactcatc gagcatcaaa tgaaactgca atttattcat atcaggatta tcaataccat 8820 atttttgaaa aagccgtttc tgtaatgaag gagaaaactc accgaggcag ttccaaagaa 8880 tggcaaggtc ctggtaacgg tctgcgattc cgacccgtcc aacatcaata caacctatta 8940 atttcccctc gtcaaaaata aggttatcaa gtgagaaatc accatgagtg acgactgaat 9000 ccggtgagaa tggcaagagc ttgtgcattt ctttccagac ttgttcaaca ggccagccat 9060 tacgctcgtc atcaaaatca ctcgcatcaa ccaaaccgtt attcatgcgt gattgcgcct 9120 gagcaagacg aaatacacga tcgctgttaa aaggacaatt acaaacagga atcgaatgta 9180 accggcgcag gaacacggcc agcgcatcaa caatattttc acctgaatca ggatattctt 9240 ctaatacctg gaaggctgtt ttcccaggaa tcgcggtggt gagtaaccac gcatcatcag 9300 gagtacggat aaaatgcttg atggtcggga gaggcataaa ctccgtcagc cagttgagac 9360 ggaccatctc atctgtaaca tcattggcaa cgctaccttt gccatgtttc agaaacaact 9420 ctggcgcatc gggcttccca tacaagcgat agattgtcgc acctgattgc ccgacattat 9480 cgcgagccca tttataccca tataaatcag cgtccatgtt ggagtttaag cgcggacggg 9540 agcaagacgt ttcccgttga atatggctca taacacccct tgtattactg tttatgtaag 9600 cagacagttt tattgttcat gatgatatat ttttatcttg tgcaatgtaa catcagagat 9660 tttgagacac aacgtggctt tgttgaataa atcgaacttt tgctgagttg aaggatcagc 9720 tctagtaaaa taataaaaaa gccggattaa taatctggct ttttatattc tctctctagt 9780 atataaacgc agaaaggccc acccgaaggt gagccagtgt gacggcacat ttccccgaaa 9840 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 9900 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 9960 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 10020 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 10080 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 10140 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 10200 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 10260 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 10320 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 10380 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 10440 cgacgttgta aaacgacggc cagtgagcgc gcggcgaatt gggtaccggg ccccc 10495 <210> 17 <211> 10493 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 17 cctcgagggc tagccattct ccctatcagt gatagagatc tatttaagcc cgagtgagca 60 cgcagtccct atcagtgata gagaggtctc cattttgaag cgggaggttt gaacgcgcag 120 ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt gacgagcatc 180 tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg gagttgccgc 240 cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg gccgagaagc 300 tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag gctcttttct 360 ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg gaaaccaccg 420 gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa ctgattcaga 480 gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca aagaccagaa 540 atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat tacttgctcc 600 ccaaaaccca gcctgagctc caatgggcat ggaccaacat ggaacagtac ctcagcgcct 660 gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac gtgtcgcaga 720 cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg atcagatcaa 780 aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg attacctcgg 840 agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg gcctccaact 900 cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc ctgactaaaa 960 ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc aatcggattt 1020 ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc tttctgggat 1080 gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct gcaactaccg 1140 ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg tgcgtaaact 1200 ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc tggtgggagg 1260 aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctcgga ggaagcaagg 1320 tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc gtgatcgtca 1380 cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc gaacaccagc 1440 agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat catgactttg 1500 ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat cacgtggttg 1560 aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc gcccccagtg 1620 acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca tcgacgtcag 1680 acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct cgtcacgtgg 1740 gcatgaatct gatgctgttt ccctgcagac aatgcgagag aatgaatcag aattcaaata 1800 tctgcttcac tcacggacag aaagactgtt tagagtgctt tcccgtgtca gaatctcaac 1860 ccgtttctgt cgtcaaaaag gcgtatcaga aactgtgcta cattcatcat atcatgggaa 1920 aggtgccaga cgcttgcact gcctgcgatc tggtcaatgt ggatttggat gactgcatct 1980 ttgaacaata aatgatttaa atcaggtatg gctgccgatg gttatcttcc agattggctc 2040 gaggacaacc tctctgaggg cattcgcgag tggtgggact tgaaacctgg agccccgaaa 2100 cccaaagcca accagcaaaa gcaggacgac ggccggggtc tggtgcttcc tggctacaag 2160 tacctcggac ccttcaacgg actcgacaag ggggagcccg tcaacgcggc ggacgcagcg 2220 gccctcgagc acgacaaggc ctacgaccag cagctcaaag cgggtgacaa tccgtacctg 2280 cggtataacc acgccgacgc cgagtttcag gagcgtctgc aagaagatac gtcttttggg 2340 ggcaacctcg ggcgagcagt cttccaggcc aagaagcggg ttctcgaacc tctcggtctg 2400 gttgaggaag gcgctaagac ggctcctgga aagaagagac cggtagagca atcaccccag 2460 gaaccagact cctcttcggg catcggcaag aaaggccagc agcccgcgag aaagagactc 2520 aactttgggc agactggcga ctcagagtca gtgcccgacc ctcaaccact cggagaaccc 2580 cccgcagccc cctctggtgt gggatctaat acaatggctg caggcggtgg cgctccaatg 2640 gcagacaata acgaaggcgc cgacggagtg ggtaacgcct caggaaattg gcattgcgat 2700 tccacatggc tgggcgacag agtcatcacc accagcaccc gaacctgggc cctccccacc 2760 tacaacaacc acctctacaa gcaaatctcc agccaatcgg gaggcagcac caacgacaac 2820 acctacttcg gctacagcac cccctggggg tattttgact ttaacagatt ccactgccac 2880 ttctcaccac gtgactggca gcgactcatc aacaacaact ggggattccg gcccaagaag 2940 ctcaacttca agctcttcaa catccaggtc aaggaggtca cgacgaatga tggcaccacg 3000 accatcgcca ataaccttac cagcacggtt caggtcttta cggactcgga ataccagctc 3060 ccgtacgtcc tcggctctgc gcaccagggc tgcctgcctc cgttcccggc ggacgtcttc 3120 atgattcctc agtacgggta cctgactctg aacaatggca gtcaggccgt gggccgttcc 3180 tccttctact gcctggaata ctttccttct caaatgctga gaacgggcaa caactttcag 3240 ttcagctaca cgtttgagga cgtgcctttt cacagcagct acgcgcacag ccaaagcctg 3300 gaccggctga tgaaccccct catcgaccag tacctgtact acctgtctcg gactcagacc 3360 acgagtggta ccgcaggaaa tcggacgttg caattttctc aggccgggcc tagtagcatg 3420 gcgaatcagg ccaaaaactg gctacccggg ccctgctacc ggcagcaacg cgtctccaag 3480 acaaccaatc aaaataacaa cagcaacttt gcctggaccg gtgccaccaa gtatcatctg 3540 aatggcagag actctctggt aaatcccggt cccgctatgg caacccacaa ggacgacgaa 3600 gacaaatttt ttccgatgag cggagtctta atatttggga aacagggagc tggaaatagc 3660 aacgtggacc ttgacaacgt tatgataacc aacgaggaag aaattaaaac caccaaccca 3720 gtggccacag aagagtacgg cacggtggcc actaacctgc aatcggccaa caccgctcct 3780 gctacaggga ccgtcaacag tcaaggagcc ttacctggca tggtctggca ggaccgggac 3840 gtgtacctgc agggtcctat ctgggccaag attcctcaca cggacggaca ctttcatccc 3900 tcgccgctga tgggaggctt tggactgaaa cacccgcctc ctcagatcct gattaagaat 3960 acacctgttc ccgcgaatcc tccaactacc ttcagtccag ctaagtttgc gtcgttcatc 4020 acgcagtaca gcaccggaca ggtcagcgtg gaaattgaat gggagctgca gaaagaaaac 4080 agcaaacgct ggaacccaga gattcaatac acttccaact acaacaaatc tacaaatgtg 4140 gactttgctg ttgacacaaa tggcgtttat tctgagcctc gccccatcgg cacccgttac 4200 ctcacccgta atctgtaaac tagtttgctt gttaatcaat aaaccgttta attcgtttca 4260 gttgaacttt ggtctctgcg tatttctttc ttatctagtt tccatgctct agaggtcctg 4320 tattagaggt cacgtgagtg ttttgcgaca ttttgcgaca ccatgtggtc acgctgggta 4380 tttaagcccg agtgagcacg cagggtctcc attttgaagc gggaggtttg aacgcgcagc 4440 cgccaagccg aattctgcag atatcggggt tggggttgcg ccttttccaa ggcagccctg 4500 ggtttgcgca gggacgcggc tgctctgggc gtggttccgg gaaacgcagc ggcgccgacc 4560 ctgggtctcg cacattcttc acgtccgttc gcagcgtcac ccggatcttc gccgctaccc 4620 ttgtgggccc cccggcgacg cttcctgctc cgcccctaag tcgggaaggt tccttgcggt 4680 tcgcggcgtg ccggacgtga caaacggaag ccgcacgtct cactagtacc ctcgcagacg 4740 gacagcgcca gggagcaatg gcagcgcgcc gaccgcgatg ggctgtggcc aatagcggct 4800 gctcagcagg gcgcgccgag agcagcggcc gggaaggggc ggtgcgggag gcggggtgtg 4860 gggcggtagt gtgggccctg ttcctgcccg cgcggtgttc cgcattctgc aagcctccgg 4920 agcgcacgtc ggcagtcggc tccctcgttg accgaatcac cgacctctct ccccagaagc 4980 tcccgggagc ttgtatatcc attttcggat ctgatcagca cgtgttgaca attaatcatc 5040 ggcatagtat atcggcatag tataatacga caaggtgagg aacgccacca tggccaagcc 5100 tttgtctcaa gaagaatcca ccctcattga aagagcaacg gctacaatca acagcatccc 5160 catctctgaa gactacagcg tcgccagcgc agctctctct agcgacggcc gcatcttcac 5220 tggtgtcaat gtatatcatt ttactggggg accttgtgca gaactcgtgg tgctgggcac 5280 tgctgctgct gcggcagctg gcaacctgac ttgtatcgtc gcgatcggaa atgagaacag 5340 gggcatcttg agcccctgcg gacggtgccg acaggtgctt ctcgatctgc atcctgggat 5400 caaagccata gtgaaggaca gtgatggaca gccgacggca gttgggattc gtgaattgct 5460 gccctctggt tatgtgtggg agggctaagc acttcgtggc cgaggagcag gactgacacg 5520 tgctacgaga tttcgattcc accgccgcct tctatgaaag gttgggcttc ggaatcgttt 5580 tccgggacgc cggctggatg atcctccagc gcggggatct catgctggag ttcttcgccc 5640 accccaactt gtttattgca gcttataatg gttacaaata aagcaatagc atcacaaatt 5700 tcacaaataa agcatttttt tcactgcatt ctagttgtgg tttgtccaaa ctcatcaatg 5760 tatcttagcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat 5820 gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctctcct aggccagaaa 5880 tggcgccgga ggcgggaaca aggtggtgga tgagtgctac atccccaatt acttgctccc 5940 caaaacccag cctgagctcc agtgggcgtg gactaatatg gaacagtatt taagcgcctg 6000 tccctatcag tgatagagat ctccctatca gtgatagaga tttgaatctc acggagcgta 6060 aacggttggt ggcgcagcat ctgtttaaac gcagacgcag gagcagaaca aagagaatca 6120 gaatcccaat tctgatgcgc cggtgatcag atcaaaaact tcagccaggt acatggagct 6180 ggtcgggtgg ctcgtggaca aggggattac ctcggagaag cagtggattc aggaggacca 6240 ggcctcatac atctccttca atgcggcctc caactcgcgg tcccaaatca aggctgcctt 6300 ggacaatgcg ggaaagatta tgagcctgac taaaaccgcc cccgactacc tggtgggcca 6360 gcagcccgtg gaggacattt ccagcaatcg gatttataaa attttggaac taaacgggta 6420 cgatccccaa tatgcggctt ccgtctttct gggatgggcc acgaaaaagt tcggcaagag 6480 gaacaccatc tggctgtttg ggcctgcaac taccgggaag accaacatcg cggaggccat 6540 agcccacact gtgcccttct acgggtgcgt aaactggacc aatgagaact ttcccttcaa 6600 cgactgtgtc gacaagatgg tgatctggtg ggaggagggg aagatgaccg ccaaggtcgt 6660 ggagtcggcc aaagccattc tcggaggaag caaggtgcgc gtggaccaga aatgcaagtc 6720 ctcggcccag atagacccga ctcccgtgat cgtcacctcc aacaccaaca tgtgcgccgt 6780 gattgacggg aactcaacga ccttcgaaca ccagcagccg ttgcaagacc ggatgttcaa 6840 atttgaactc acccgccgtc tggatcatga ctttgggaag gtcaccaagc aggaagtcaa 6900 agactttttc cggtgggcaa aggatcacgt ggttgaggtg gagcatgaat tctacgtcaa 6960 aaagggtgga gccaagaaaa gacccgcccc cagtgacgca gatataagtg agcccaaacg 7020 ggtgcgcgag tcagttgcgc agccatcgac gtcagacgcg gaagcttcga tcaactacgc 7080 agacaggtac caaaacaaat gttctcgtca cgtgggcatg aatctgatgc tgtttccctg 7140 cagacaatgc gagagaatga atcagaattc aaatatctgc ttcactcacg gacagaaaga 7200 ctgtttagag tgctttcccg tgtcagaatc tcaacccgtt tctgtcgtca aaaaggcgta 7260 tcagaaactg tgctacattc atcatatcat gggaaaggtg ccagacgctt gcactgcctg 7320 cgatctggtc aatgtggatt tggatgactg catctttgaa caataaacta gtttgcttgt 7380 taatcaataa accgtttaat tcgtttcagt tgaactttgg tctctgcgta tttctttctt 7440 atctagtttc catgctctag agtatacgat atccatcaca ctggcggccg ctcgactaga 7500 gcggccgcca ccgcggtgga gctccagctt ttgttcgcgc gcttggcgta atcatggtca 7560 tagctgtttc ctgtgtgaaa ttccacagcc tggggtgcct aattgcgttg cgctcactgc 7620 ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc caacgcgcgg 7680 ggagaggcgg tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct 7740 cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 7800 cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 7860 accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 7920 acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 7980 cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 8040 acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 8100 atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 8160 agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 8220 acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 8280 gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 8340 gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 8400 gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 8460 gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 8520 acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 8580 tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 8640 ctgacagaaa taataaaaaa gccggattaa taatctggct ttttatattc tctctctagt 8700 atataaacgc agaaaggccc acccgaaggt gagccagtgt gactctagta ttattagaaa 8760 aactcatcga gcatcaaatg aaactgcaat ttattcatat caggattatc aataccatat 8820 ttttgaaaaa gccgtttctg taatgaagga gaaaactcac cgaggcagtt ccaaagaatg 8880 gcaaggtcct ggtaacggtc tgcgattccg acccgtccaa catcaataca acctattaat 8940 ttcccctcgt caaaaataag gttatcaagt gagaaatcac catgagtgac gactgaatcc 9000 ggtgagaatg gcaagagctt gtgcatttct ttccagactt gttcaacagg ccagccatta 9060 cgctcgtcat caaaatcact cgcatcaacc aaaccgttat tcatgcgtga ttgcgcctga 9120 gcaagacgaa atacacgatc gctgttaaaa ggacaattac aaacaggaat cgaatgtaac 9180 cggcgcagga acacggccag cgcatcaaca atattttcac ctgaatcagg atattcttct 9240 aatacctgga aggctgtttt cccaggaatc gcggtggtga gtaaccacgc atcatcagga 9300 gtacggataa aatgcttgat ggtcgggaga ggcataaact ccgtcagcca gttgagacgg 9360 accatctcat ctgtaacatc attggcaacg ctacctttgc catgtttcag aaacaactct 9420 ggcgcatcgg gcttcccata caagcgatag attgtcgcac ctgattgccc gacattatcg 9480 cgagcccatt tatacccata taaatcagcg tccatgttgg agtttaagcg cggacgggag 9540 caagacgttt cccgttgaat atggctcata acaccccttg tattactgtt tatgtaagca 9600 gacagtttta ttgttcatga tgatatattt ttatcttgtg caatgtaaca tcagagattt 9660 tgagacacaa cgtggctttg ttgaataaat cgaacttttg ctgagttgaa ggatcagctc 9720 tagtaaaata ataaaaaagc cggattaata atctggcttt ttatattctc tctctagtat 9780 ataaacgcag aaaggcccac ccgaaggtga gccagtgtga cggcacattt ccccgaaaag 9840 tgccacctaa attgtaagcg ttaatatttt gttaaaattc gcgttaaatt tttgttaaat 9900 cagctcattt tttaaccaat aggccgaaat cggcaaaatc ccttataaat caaaagaata 9960 gaccgagata gggttgagtg ttgttccagt ttggaacaag agtccactat taaagaacgt 10020 ggactccaac gtcaaagggc gaaaaaccgt ctatcagggc gatggcccac tacgtgaacc 10080 atcaccctaa tcaagttttt tggggtcgag gtgccgtaaa gcactaaatc ggaaccctaa 10140 agggagcccc cgatttagag cttgacgggg aaagccggcg aacgtggcga gaaaggaagg 10200 gaagaaagcg aaaggagcgg gcgctagggc gctggcaagt gtagcggtca cgctgcgcgt 10260 aaccaccaca cccgccgcgc ttaatgcgcc gctacagggc gcgtcccatt cgccattcag 10320 gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac gccagctggc 10380 gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt cccagtcacg 10440 acgttgtaaa acgacggcca gtgagcgcgc ggcgaattgg gtaccgggcc ccc 10493 <210> 18 <211> 10495 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 18 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatct ccctatcagt 60 gatagagatc gcccgagtga gcacgcaggg tctccatttt gaagcgggag gtttgaacgc 120 gcagccgcca tgccggggtt ttacgagatt gtgattaagg tccccagcga ccttgacgag 180 catctgcccg gcatttctga cagctttgtg aactgggtgg ccgagaagga atgggagttg 240 ccgccagatt ctgacatgga tctgaatctg attgagcagg cacccctgac cgtggccgag 300 aagctgcagc gcgactttct gacggaatgg cgccgtgtga gtaaggcccc ggaggctctt 360 ttctttgtgc aatttgagaa gggagagagc tacttccaca tgcacgtgct cgtggaaacc 420 accggggtga aatccatggt tttgggacgt ttcctgagtc agattcgcga aaaactgatt 480 cagagaattt accgcgggat cgagccgact ttgccaaact ggttcgcggt cacaaagacc 540 agaaatggcg ccggaggcgg gaacaaggtg gtggatgagt gctacatccc caattacttg 600 ctccccaaaa cccagcctga gctccaatgg gcatggacca acatggaaca gtacctcagc 660 gcctgtttga atctcacgga gcgtaaacgg ttggtggcgc agcatctgac gcacgtgtcg 720 cagacgcagg agcagaacaa agagaatcag aatcccaatt ctgatgcgcc ggtgatcaga 780 tcaaaaactt cagccaggta catggagctg gtcgggtggc tcgtggacaa ggggattacc 840 tcggagaagc agtggatcca ggaggaccag gcctcataca tctccttcaa tgcggcctcc 900 aactcgcggt cccaaatcaa ggctgccttg gacaatgcgg gaaagattat gagcctgact 960 aaaaccgccc ccgactacct ggtgggccag cagcccgtgg aggacatttc cagcaatcgg 1020 atttataaaa ttttggaact aaacgggtac gatccccaat atgcggcttc cgtctttctg 1080 ggatgggcca cgaaaaagtt cggcaagagg aacaccatct ggctgtttgg gcctgcaact 1140 accgggaaga ccaacatcgc ggaggccata gcccacactg tgcccttcta cgggtgcgta 1200 aactggacca atgagaactt tcccttcaac gactgtgtcg acaagatggt gatctggtgg 1260 gaggagggga agatgaccgc caaggtcgtg gagtcggcca aagccattct cggaggaagc 1320 aaggtgcgcg tggaccagaa atgcaagtcc tcggcccaga tagacccgac tcccgtgatc 1380 gtcacctcca acaccaacat gtgcgccgtg attgacggga actcaacgac cttcgaacac 1440 cagcagccgt tgcaagaccg gatgttcaaa tttgaactca cccgccgtct ggatcatgac 1500 tttgggaagg tcaccaagca ggaagtcaaa gactttttcc ggtgggcaaa ggatcacgtg 1560 gttgaggtgg agcatgaatt ctacgtcaaa aagggtggag ccaagaaaag acccgccccc 1620 agtgacgcag atataagtga gcccaaacgg gtgcgcgagt cagttgcgca gccatcgacg 1680 tcagacgcgg aagcttcgat caactacgca gacaggtacc aaaacaaatg ttctcgtcac 1740 gtgggcatga atctgatgct gtttccctgc agacaatgcg agagaatgaa tcagaattca 1800 aatatctgct tcactcacgg acagaaagac tgtttagagt gctttcccgt gtcagaatct 1860 caacccgttt ctgtcgtcaa aaaggcgtat cagaaactgt gctacattca tcatatcatg 1920 ggaaaggtgc cagacgcttg cactgcctgc gatctggtca atgtggattt ggatgactgc 1980 atctttgaac aataaatgat ttaaatcagg tatggctgcc gatggttatc ttccagattg 2040 gctcgaggac aacctctctg agggcattcg cgagtggtgg gacttgaaac ctggagcccc 2100 gaaacccaaa gccaaccagc aaaagcagga cgacggccgg ggtctggtgc ttcctggcta 2160 caagtacctc ggacccttca acggactcga caagggggag cccgtcaacg cggcggacgc 2220 agcggccctc gagcacgaca aggcctacga ccagcagctc aaagcgggtg acaatccgta 2280 cctgcggtat aaccacgccg acgccgagtt tcaggagcgt ctgcaagaag atacgtcttt 2340 tgggggcaac ctcgggcgag cagtcttcca ggccaagaag cgggttctcg aacctctcgg 2400 tctggttgag gaaggcgcta agacggctcc tggaaagaag agaccggtag agcaatcacc 2460 ccaggaacca gactcctctt cgggcatcgg caagaaaggc cagcagcccg cgagaaagag 2520 actcaacttt gggcagactg gcgactcaga gtcagtgccc gaccctcaac cactcggaga 2580 accccccgca gccccctctg gtgtgggatc taatacaatg gctgcaggcg gtggcgctcc 2640 aatggcagac aataacgaag gcgccgacgg agtgggtaac gcctcaggaa attggcattg 2700 cgattccaca tggctgggcg acagagtcat caccaccagc acccgaacct gggccctccc 2760 cacctacaac aaccacctct acaagcaaat ctccagccaa tcgggaggca gcaccaacga 2820 caacacctac ttcggctaca gcaccccctg ggggtatttt gactttaaca gattccactg 2880 ccacttctca ccacgtgact ggcagcgact catcaacaac aactggggat tccggcccaa 2940 gaagctcaac ttcaagctct tcaacatcca ggtcaaggag gtcacgacga atgatggcac 3000 cacgaccatc gccaataacc ttaccagcac ggttcaggtc tttacggact cggaatacca 3060 gctcccgtac gtcctcggct ctgcgcacca gggctgcctg cctccgttcc cggcggacgt 3120 cttcatgatt cctcagtacg ggtacctgac tctgaacaat ggcagtcagg ccgtgggccg 3180 ttcctccttc tactgcctgg aatactttcc ttctcaaatg ctgagaacgg gcaacaactt 3240 tcagttcagc tacacgtttg aggacgtgcc ttttcacagc agctacgcgc acagccaaag 3300 cctggaccgg ctgatgaacc ccctcatcga ccagtacctg tactacctgt ctcggactca 3360 gaccacgagt ggtaccgcag gaaatcggac gttgcaattt tctcaggccg ggcctagtag 3420 catggcgaat caggccaaaa actggctacc cgggccctgc taccggcagc aacgcgtctc 3480 caagacaacc aatcaaaata acaacagcaa ctttgcctgg accggtgcca ccaagtatca 3540 tctgaatggc agagactctc tggtaaatcc cggtcccgct atggcaaccc acaaggacga 3600 cgaagacaaa ttttttccga tgagcggagt cttaatattt gggaaacagg gagctggaaa 3660 tagcaacgtg gaccttgaca acgttatgat aaccaacgag gaagaaatta aaaccaccaa 3720 cccagtggcc acagaagagt acggcacggt ggccactaac ctgcaatcgg ccaacaccgc 3780 tcctgctaca gggaccgtca acagtcaagg agccttacct ggcatggtct ggcaggaccg 3840 ggacgtgtac ctgcagggtc ctatctgggc caagattcct cacacggacg gacactttca 3900 tccctcgccg ctgatgggag gctttggact gaaacacccg cctcctcaga tcctgattaa 3960 gaatacacct gttcccgcga atcctccaac taccttcagt ccagctaagt ttgcgtcgtt 4020 catcacgcag tacagcaccg gacaggtcag cgtggaaatt gaatgggagc tgcagaaaga 4080 aaacagcaaa cgctggaacc cagagattca atacacttcc aactacaaca aatctacaaa 4140 tgtggacttt gctgttgaca caaatggcgt ttattctgag cctcgcccca tcggcacccg 4200 ttacctcacc cgtaatctgt aaactagttt gcttgttaat caataaaccg tttaattcgt 4260 ttcagttgaa ctttggtctc tgcgtatttc tttcttatct agtttccatg ctctagaggt 4320 cctgtattag aggtcacgtg agtgttttgc gacattttgc gacaccatgt ggtcacgctg 4380 ggtatttaag cccgagtgag cacgcagggt ctccattttg aagcgggagg tttgaacgcg 4440 cagccgccaa gccgaattct gcagatatcg gggttggggt tgcgcctttt ccaaggcagc 4500 cctgggtttg cgcagggacg cggctgctct gggcgtggtt ccgggaaacg cagcggcgcc 4560 gaccctgggt ctcgcacatt cttcacgtcc gttcgcagcg tcacccggat cttcgccgct 4620 acccttgtgg gccccccggc gacgcttcct gctccgcccc taagtcggga aggttccttg 4680 cggttcgcgg cgtgccggac gtgacaaacg gaagccgcac gtctcactag taccctcgca 4740 gacggacagc gccagggagc aatggcagcg cgccgaccgc gatgggctgt ggccaatagc 4800 ggctgctcag cagggcgcgc cgagagcagc ggccgggaag gggcggtgcg ggaggcgggg 4860 tgtggggcgg tagtgtgggc cctgttcctg cccgcgcggt gttccgcatt ctgcaagcct 4920 ccggagcgca cgtcggcagt cggctccctc gttgaccgaa tcaccgacct ctctccccag 4980 aagctcccgg gagcttgtat atccattttc ggatctgatc agcacgtgtt gacaattaat 5040 catcggcata gtatatcggc atagtataat acgacaaggt gaggaacgcc accatggcca 5100 agcctttgtc tcaagaagaa tccaccctca ttgaaagagc aacggctaca atcaacagca 5160 tccccatctc tgaagactac agcgtcgcca gcgcagctct ctctagcgac ggccgcatct 5220 tcactggtgt caatgtatat cattttactg ggggaccttg tgcagaactc gtggtgctgg 5280 gcactgctgc tgctgcggca gctggcaacc tgacttgtat cgtcgcgatc ggaaatgaga 5340 acaggggcat cttgagcccc tgcggacggt gccgacaggt gcttctcgat ctgcatcctg 5400 ggatcaaagc catagtgaag gacagtgatg gacagccgac ggcagttggg attcgtgaat 5460 tgctgccctc tggttatgtg tgggagggct aagcacttcg tggccgagga gcaggactga 5520 cacgtgctac gagatttcga ttccaccgcc gccttctatg aaaggttggg cttcggaatc 5580 gttttccggg acgccggctg gatgatcctc cagcgcgggg atctcatgct ggagttcttc 5640 gcccacccca acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 5700 aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 5760 aatgtatctt agcgctcact gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat 5820 taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc tcctaggcca 5880 gaaatggcgc cggaggcggg aacaaggtgg tggatgagtg ctacatcccc aattacttgc 5940 tccccaaaac ccagcctgag tccctatcag tgatagagac tccagtgggc gtggactaat 6000 atggaacagt atttaagcgc ctgtccctat cagtgataga gatttgaatc tcacggagcg 6060 taaacggttg gtggcgcagc atctgtttaa acgcagacgc aggagcagaa caaagagaat 6120 cagaatccca attctgatgc gccggtgatc agatcaaaaa cttcagccag gtacatggag 6180 ctggtcgggt ggctcgtgga caaggggatt acctcggaga agcagtggat tcaggaggac 6240 caggcctcat acatctcctt caatgcggcc tccaactcgc ggtcccaaat caaggctgcc 6300 ttggacaatg cgggaaagat tatgagcctg actaaaaccg cccccgacta cctggtgggc 6360 cagcagcccg tggaggacat ttccagcaat cggatttata aaattttgga actaaacggg 6420 tacgatcccc aatatgcggc ttccgtcttt ctgggatggg ccacgaaaaa gttcggcaag 6480 aggaacacca tctggctgtt tgggcctgca actaccggga agaccaacat cgcggaggcc 6540 atagcccaca ctgtgccctt ctacgggtgc gtaaactgga ccaatgagaa ctttcccttc 6600 aacgactgtg tcgacaagat ggtgatctgg tgggaggagg ggaagatgac cgccaaggtc 6660 gtggagtcgg ccaaagccat tctcggagga agcaaggtgc gcgtggacca gaaatgcaag 6720 tcctcggccc agatagaccc gactcccgtg atcgtcacct ccaacaccaa catgtgcgcc 6780 gtgattgacg ggaactcaac gaccttcgaa caccagcagc cgttgcaaga ccggatgttc 6840 aaatttgaac tcacccgccg tctggatcat gactttggga aggtcaccaa gcaggaagtc 6900 aaagactttt tccggtgggc aaaggatcac gtggttgagg tggagcatga attctacgtc 6960 aaaaagggtg gagccaagaa aagacccgcc cccagtgacg cagatataag tgagcccaaa 7020 cgggtgcgcg agtcagttgc gcagccatcg acgtcagacg cggaagcttc gatcaactac 7080 gcagacaggt accaaaacaa atgttctcgt cacgtgggca tgaatctgat gctgtttccc 7140 tgcagacaat gcgagagaat gaatcagaat tcaaatatct gcttcactca cggacagaaa 7200 gactgtttag agtgctttcc cgtgtcagaa tctcaacccg tttctgtcgt caaaaaggcg 7260 tatcagaaac tgtgctacat tcatcatatc atgggaaagg tgccagacgc ttgcactgcc 7320 tgcgatctgg tcaatgtgga tttggatgac tgcatctttg aacaataaac tagtttgctt 7380 gttaatcaat aaaccgttta attcgtttca gttgaacttt ggtctctgcg tatttctttc 7440 ttatctagtt tccatgctct agagtatacg atatccatca cactggcggc cgctcgacta 7500 gagcggccgc caccgcggtg gagctccagc ttttgttcgc gcgcttggcg taatcatggt 7560 catagctgtt tcctgtgtga aattccacag cctggggtgc ctaattgcgt tgcgctcact 7620 gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc 7680 ggggagaggc ggtttgcgta ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg 7740 ctcggtcgtt cggctgcggc gagcggtatc agctcactca aaggcggtaa tacggttatc 7800 cacagaatca ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag 7860 gaaccgtaaa aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca 7920 tcacaaaaat cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca 7980 ggcgtttccc cctggaagct ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg 8040 atacctgtcc gcctttctcc cttcgggaag cgtggcgctt tctcatagct cacgctgtag 8100 gtatctcagt tcggtgtagg tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt 8160 tcagcccgac cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc cggtaagaca 8220 cgacttatcg ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg 8280 cggtgctaca gagttcttga agtggtggcc taactacggc tacactagaa gaacagtatt 8340 tggtatctgc gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc 8400 cggcaaacaa accaccgctg gtagcggtgg tttttttgtt tgcaagcagc agattacgcg 8460 cagaaaaaaa ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg 8520 gaacgaaaac tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta 8580 gatcctttta aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg 8640 gtctgacaga aataataaaa aagccggatt aataatctgg ctttttatat tctctctcta 8700 gtatataaac gcagaaaggc ccacccgaag gtgagccagt gtgactctag tattattaga 8760 aaaactcatc gagcatcaaa tgaaactgca atttattcat atcaggatta tcaataccat 8820 atttttgaaa aagccgtttc tgtaatgaag gagaaaactc accgaggcag ttccaaagaa 8880 tggcaaggtc ctggtaacgg tctgcgattc cgacccgtcc aacatcaata caacctatta 8940 atttcccctc gtcaaaaata aggttatcaa gtgagaaatc accatgagtg acgactgaat 9000 ccggtgagaa tggcaagagc ttgtgcattt ctttccagac ttgttcaaca ggccagccat 9060 tacgctcgtc atcaaaatca ctcgcatcaa ccaaaccgtt attcatgcgt gattgcgcct 9120 gagcaagacg aaatacacga tcgctgttaa aaggacaatt acaaacagga atcgaatgta 9180 accggcgcag gaacacggcc agcgcatcaa caatattttc acctgaatca ggatattctt 9240 ctaatacctg gaaggctgtt ttcccaggaa tcgcggtggt gagtaaccac gcatcatcag 9300 gagtacggat aaaatgcttg atggtcggga gaggcataaa ctccgtcagc cagttgagac 9360 ggaccatctc atctgtaaca tcattggcaa cgctaccttt gccatgtttc agaaacaact 9420 ctggcgcatc gggcttccca tacaagcgat agattgtcgc acctgattgc ccgacattat 9480 cgcgagccca tttataccca tataaatcag cgtccatgtt ggagtttaag cgcggacggg 9540 agcaagacgt ttcccgttga atatggctca taacacccct tgtattactg tttatgtaag 9600 cagacagttt tattgttcat gatgatatat ttttatcttg tgcaatgtaa catcagagat 9660 tttgagacac aacgtggctt tgttgaataa atcgaacttt tgctgagttg aaggatcagc 9720 tctagtaaaa taataaaaaa gccggattaa taatctggct ttttatattc tctctctagt 9780 atataaacgc agaaaggccc acccgaaggt gagccagtgt gacggcacat ttccccgaaa 9840 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 9900 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 9960 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 10020 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 10080 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 10140 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 10200 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 10260 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 10320 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 10380 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 10440 cgacgttgta aaacgacggc cagtgagcgc gcggcgaatt gggtaccggg ccccc 10495 <210> 19 <211> 10493 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 19 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatcg cccgagtgag 60 cacgcagggt ctccattttg atccctatca gtgatagaga agcgggaggt ttgaacgcgc 120 agccgccatg ccggggtttt acgagattgt gattaaggtc cccagcgacc ttgacgagca 180 tctgcccggc atttctgaca gctttgtgaa ctgggtggcc gagaaggaat gggagttgcc 240 gccagattct gacatggatc tgaatctgat tgagcaggca cccctgaccg tggccgagaa 300 gctgcagcgc gactttctga cggaatggcg ccgtgtgagt aaggccccgg aggctctttt 360 ctttgtgcaa tttgagaagg gagagagcta cttccacatg cacgtgctcg tggaaaccac 420 cggggtgaaa tccatggttt tgggacgttt cctgagtcag attcgcgaaa aactgattca 480 gagaatttac cgcgggatcg agccgacttt gccaaactgg ttcgcggtca caaagaccag 540 aaatggcgcc ggaggcggga acaaggtggt ggatgagtgc tacatcccca attacttgct 600 ccccaaaacc cagcctgagc tccaatgggc atggaccaac atggaacagt acctcagcgc 660 ctgtttgaat ctcacggagc gtaaacggtt ggtggcgcag catctgacgc acgtgtcgca 720 gacgcaggag cagaacaaag agaatcagaa tcccaattct gatgcgccgg tgatcagatc 780 aaaaacttca gccaggtaca tggagctggt cgggtggctc gtggacaagg ggattacctc 840 ggagaagcag tggatccagg aggaccaggc ctcatacatc tccttcaatg cggcctccaa 900 ctcgcggtcc caaatcaagg ctgccttgga caatgcggga aagattatga gcctgactaa 960 aaccgccccc gactacctgg tgggccagca gcccgtggag gacatttcca gcaatcggat 1020 ttataaaatt ttggaactaa acgggtacga tccccaatat gcggcttccg tctttctggg 1080 atgggccacg aaaaagttcg gcaagaggaa caccatctgg ctgtttgggc ctgcaactac 1140 cgggaagacc aacatcgcgg aggccatagc ccacactgtg cccttctacg ggtgcgtaaa 1200 ctggaccaat gagaactttc ccttcaacga ctgtgtcgac aagatggtga tctggtggga 1260 ggaggggaag atgaccgcca aggtcgtgga gtcggccaaa gccattctcg gaggaagcaa 1320 ggtgcgcgtg gaccagaaat gcaagtcctc ggcccagata gacccgactc ccgtgatcgt 1380 cacctccaac accaacatgt gcgccgtgat tgacgggaac tcaacgacct tcgaacacca 1440 gcagccgttg caagaccgga tgttcaaatt tgaactcacc cgccgtctgg atcatgactt 1500 tgggaaggtc accaagcagg aagtcaaaga ctttttccgg tgggcaaagg atcacgtggt 1560 tgaggtggag catgaattct acgtcaaaaa gggtggagcc aagaaaagac ccgcccccag 1620 tgacgcagat ataagtgagc ccaaacgggt gcgcgagtca gttgcgcagc catcgacgtc 1680 agacgcggaa gcttcgatca actacgcaga caggtaccaa aacaaatgtt ctcgtcacgt 1740 gggcatgaat ctgatgctgt ttccctgcag acaatgcgag agaatgaatc agaattcaaa 1800 tatctgcttc actcacggac agaaagactg tttagagtgc tttcccgtgt cagaatctca 1860 acccgtttct gtcgtcaaaa aggcgtatca gaaactgtgc tacattcatc atatcatggg 1920 aaaggtgcca gacgcttgca ctgcctgcga tctggtcaat gtggatttgg atgactgcat 1980 ctttgaacaa taaatgattt aaatcaggta tggctgccga tggttatctt ccagattggc 2040 tcgaggacaa cctctctgag ggcattcgcg agtggtggga cttgaaacct ggagccccga 2100 aacccaaagc caaccagcaa aagcaggacg acggccgggg tctggtgctt cctggctaca 2160 agtacctcgg acccttcaac ggactcgaca agggggagcc cgtcaacgcg gcggacgcag 2220 cggccctcga gcacgacaag gcctacgacc agcagctcaa agcgggtgac aatccgtacc 2280 tgcggtataa ccacgccgac gccgagtttc aggagcgtct gcaagaagat acgtcttttg 2340 ggggcaacct cgggcgagca gtcttccagg ccaagaagcg ggttctcgaa cctctcggtc 2400 tggttgagga aggcgctaag acggctcctg gaaagaagag accggtagag caatcacccc 2460 aggaaccaga ctcctcttcg ggcatcggca agaaaggcca gcagcccgcg agaaagagac 2520 tcaactttgg gcagactggc gactcagagt cagtgcccga ccctcaacca ctcggagaac 2580 cccccgcagc cccctctggt gtgggatcta atacaatggc tgcaggcggt ggcgctccaa 2640 tggcagacaa taacgaaggc gccgacggag tgggtaacgc ctcaggaaat tggcattgcg 2700 attccacatg gctgggcgac agagtcatca ccaccagcac ccgaacctgg gccctcccca 2760 cctacaacaa ccacctctac aagcaaatct ccagccaatc gggaggcagc accaacgaca 2820 acacctactt cggctacagc accccctggg ggtattttga ctttaacaga ttccactgcc 2880 acttctcacc acgtgactgg cagcgactca tcaacaacaa ctggggattc cggcccaaga 2940 agctcaactt caagctcttc aacatccagg tcaaggaggt cacgacgaat gatggcacca 3000 cgaccatcgc caataacctt accagcacgg ttcaggtctt tacggactcg gaataccagc 3060 tcccgtacgt cctcggctct gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct 3120 tcatgattcc tcagtacggg tacctgactc tgaacaatgg cagtcaggcc gtgggccgtt 3180 cctccttcta ctgcctggaa tactttcctt ctcaaatgct gagaacgggc aacaactttc 3240 agttcagcta cacgtttgag gacgtgcctt ttcacagcag ctacgcgcac agccaaagcc 3300 tggaccggct gatgaacccc ctcatcgacc agtacctgta ctacctgtct cggactcaga 3360 ccacgagtgg taccgcagga aatcggacgt tgcaattttc tcaggccggg cctagtagca 3420 tggcgaatca ggccaaaaac tggctacccg ggccctgcta ccggcagcaa cgcgtctcca 3480 agacaaccaa tcaaaataac aacagcaact ttgcctggac cggtgccacc aagtatcatc 3540 tgaatggcag agactctctg gtaaatcccg gtcccgctat ggcaacccac aaggacgacg 3600 aagacaaatt ttttccgatg agcggagtct taatatttgg gaaacaggga gctggaaata 3660 gcaacgtgga ccttgacaac gttatgataa ccaacgagga agaaattaaa accaccaacc 3720 cagtggccac agaagagtac ggcacggtgg ccactaacct gcaatcggcc aacaccgctc 3780 ctgctacagg gaccgtcaac agtcaaggag ccttacctgg catggtctgg caggaccggg 3840 acgtgtacct gcagggtcct atctgggcca agattcctca cacggacgga cactttcatc 3900 cctcgccgct gatgggaggc tttggactga aacacccgcc tcctcagatc ctgattaaga 3960 atacacctgt tcccgcgaat cctccaacta ccttcagtcc agctaagttt gcgtcgttca 4020 tcacgcagta cagcaccgga caggtcagcg tggaaattga atgggagctg cagaaagaaa 4080 acagcaaacg ctggaaccca gagattcaat acacttccaa ctacaacaaa tctacaaatg 4140 tggactttgc tgttgacaca aatggcgttt attctgagcc tcgccccatc ggcacccgtt 4200 acctcacccg taatctgtaa actagtttgc ttgttaatca ataaaccgtt taattcgttt 4260 cagttgaact ttggtctctg cgtatttctt tcttatctag tttccatgct ctagaggtcc 4320 tgtattagag gtcacgtgag tgttttgcga cattttgcga caccatgtgg tcacgctggg 4380 tatttaagcc cgagtgagca cgcagggtct ccattttgaa gcgggaggtt tgaacgcgca 4440 gccgccaagc cgaattctgc agatatcggg gttggggttg cgccttttcc aaggcagccc 4500 tgggtttgcg cagggacgcg gctgctctgg gcgtggttcc gggaaacgca gcggcgccga 4560 ccctgggtct cgcacattct tcacgtccgt tcgcagcgtc acccggatct tcgccgctac 4620 ccttgtgggc cccccggcga cgcttcctgc tccgccccta agtcgggaag gttccttgcg 4680 gttcgcggcg tgccggacgt gacaaacgga agccgcacgt ctcactagta ccctcgcaga 4740 cggacagcgc cagggagcaa tggcagcgcg ccgaccgcga tgggctgtgg ccaatagcgg 4800 ctgctcagca gggcgcgccg agagcagcgg ccgggaaggg gcggtgcggg aggcggggtg 4860 tggggcggta gtgtgggccc tgttcctgcc cgcgcggtgt tccgcattct gcaagcctcc 4920 ggagcgcacg tcggcagtcg gctccctcgt tgaccgaatc accgacctct ctccccagaa 4980 gctcccggga gcttgtatat ccattttcgg atctgatcag cacgtgttga caattaatca 5040 tcggcatagt atatcggcat agtataatac gacaaggtga ggaacgccac catggccaag 5100 cctttgtctc aagaagaatc caccctcatt gaaagagcaa cggctacaat caacagcatc 5160 cccatctctg aagactacag cgtcgccagc gcagctctct ctagcgacgg ccgcatcttc 5220 actggtgtca atgtatatca ttttactggg ggaccttgtg cagaactcgt ggtgctgggc 5280 actgctgctg ctgcggcagc tggcaacctg acttgtatcg tcgcgatcgg aaatgagaac 5340 aggggcatct tgagcccctg cggacggtgc cgacaggtgc ttctcgatct gcatcctggg 5400 atcaaagcca tagtgaagga cagtgatgga cagccgacgg cagttgggat tcgtgaattg 5460 ctgccctctg gttatgtgtg ggagggctaa gcacttcgtg gccgaggagc aggactgaca 5520 cgtgctacga gatttcgatt ccaccgccgc cttctatgaa aggttgggct tcggaatcgt 5580 tttccgggac gccggctgga tgatcctcca gcgcggggat ctcatgctgg agttcttcgc 5640 ccaccccaac ttgtttattg cagcttataa tggttacaaa taaagcaata gcatcacaaa 5700 tttcacaaat aaagcatttt tttcactgca ttctagttgt ggtttgtcca aactcatcaa 5760 tgtatcttag cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta 5820 atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctc ctaggccaga 5880 aatggcgccg gaggcgggaa caaggtggtg gatgagtgct acatccccaa ttacttgctc 5940 cccaaaaccc agcctgagtc cctatcagtg atagagactc cagtgggcgt ggactaatat 6000 ggaacagtat ttaagcgcct gtccctatca gtgatagaga tttgaatctc acggagcgta 6060 aacggttggt ggcgcagcat ctgtttaaac gcagacgcag gagcagaaca aagagaatca 6120 gaatcccaat tctgatgcgc cggtgatcag atcaaaaact tcagccaggt acatggagct 6180 ggtcgggtgg ctcgtggaca aggggattac ctcggagaag cagtggattc aggaggacca 6240 ggcctcatac atctccttca atgcggcctc caactcgcgg tcccaaatca aggctgcctt 6300 ggacaatgcg ggaaagatta tgagcctgac taaaaccgcc cccgactacc tggtgggcca 6360 gcagcccgtg gaggacattt ccagcaatcg gatttataaa attttggaac taaacgggta 6420 cgatccccaa tatgcggctt ccgtctttct gggatgggcc acgaaaaagt tcggcaagag 6480 gaacaccatc tggctgtttg ggcctgcaac taccgggaag accaacatcg cggaggccat 6540 agcccacact gtgcccttct acgggtgcgt aaactggacc aatgagaact ttcccttcaa 6600 cgactgtgtc gacaagatgg tgatctggtg ggaggagggg aagatgaccg ccaaggtcgt 6660 ggagtcggcc aaagccattc tcggaggaag caaggtgcgc gtggaccaga aatgcaagtc 6720 ctcggcccag atagacccga ctcccgtgat cgtcacctcc aacaccaaca tgtgcgccgt 6780 gattgacggg aactcaacga ccttcgaaca ccagcagccg ttgcaagacc ggatgttcaa 6840 atttgaactc acccgccgtc tggatcatga ctttgggaag gtcaccaagc aggaagtcaa 6900 agactttttc cggtgggcaa aggatcacgt ggttgaggtg gagcatgaat tctacgtcaa 6960 aaagggtgga gccaagaaaa gacccgcccc cagtgacgca gatataagtg agcccaaacg 7020 ggtgcgcgag tcagttgcgc agccatcgac gtcagacgcg gaagcttcga tcaactacgc 7080 agacaggtac caaaacaaat gttctcgtca cgtgggcatg aatctgatgc tgtttccctg 7140 cagacaatgc gagagaatga atcagaattc aaatatctgc ttcactcacg gacagaaaga 7200 ctgtttagag tgctttcccg tgtcagaatc tcaacccgtt tctgtcgtca aaaaggcgta 7260 tcagaaactg tgctacattc atcatatcat gggaaaggtg ccagacgctt gcactgcctg 7320 cgatctggtc aatgtggatt tggatgactg catctttgaa caataaacta gtttgcttgt 7380 taatcaataa accgtttaat tcgtttcagt tgaactttgg tctctgcgta tttctttctt 7440 atctagtttc catgctctag agtatacgat atccatcaca ctggcggccg ctcgactaga 7500 gcggccgcca ccgcggtgga gctccagctt ttgttcgcgc gcttggcgta atcatggtca 7560 tagctgtttc ctgtgtgaaa ttccacagcc tggggtgcct aattgcgttg cgctcactgc 7620 ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc caacgcgcgg 7680 ggagaggcgg tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct 7740 cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 7800 cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 7860 accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 7920 acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 7980 cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 8040 acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 8100 atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 8160 agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 8220 acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 8280 gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 8340 gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 8400 gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 8460 gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 8520 acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 8580 tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 8640 ctgacagaaa taataaaaaa gccggattaa taatctggct ttttatattc tctctctagt 8700 atataaacgc agaaaggccc acccgaaggt gagccagtgt gactctagta ttattagaaa 8760 aactcatcga gcatcaaatg aaactgcaat ttattcatat caggattatc aataccatat 8820 ttttgaaaaa gccgtttctg taatgaagga gaaaactcac cgaggcagtt ccaaagaatg 8880 gcaaggtcct ggtaacggtc tgcgattccg acccgtccaa catcaataca acctattaat 8940 ttcccctcgt caaaaataag gttatcaagt gagaaatcac catgagtgac gactgaatcc 9000 ggtgagaatg gcaagagctt gtgcatttct ttccagactt gttcaacagg ccagccatta 9060 cgctcgtcat caaaatcact cgcatcaacc aaaccgttat tcatgcgtga ttgcgcctga 9120 gcaagacgaa atacacgatc gctgttaaaa ggacaattac aaacaggaat cgaatgtaac 9180 cggcgcagga acacggccag cgcatcaaca atattttcac ctgaatcagg atattcttct 9240 aatacctgga aggctgtttt cccaggaatc gcggtggtga gtaaccacgc atcatcagga 9300 gtacggataa aatgcttgat ggtcgggaga ggcataaact ccgtcagcca gttgagacgg 9360 accatctcat ctgtaacatc attggcaacg ctacctttgc catgtttcag aaacaactct 9420 ggcgcatcgg gcttcccata caagcgatag attgtcgcac ctgattgccc gacattatcg 9480 cgagcccatt tatacccata taaatcagcg tccatgttgg agtttaagcg cggacgggag 9540 caagacgttt cccgttgaat atggctcata acaccccttg tattactgtt tatgtaagca 9600 gacagtttta ttgttcatga tgatatattt ttatcttgtg caatgtaaca tcagagattt 9660 tgagacacaa cgtggctttg ttgaataaat cgaacttttg ctgagttgaa ggatcagctc 9720 tagtaaaata ataaaaaagc cggattaata atctggcttt ttatattctc tctctagtat 9780 ataaacgcag aaaggcccac ccgaaggtga gccagtgtga cggcacattt ccccgaaaag 9840 tgccacctaa attgtaagcg ttaatatttt gttaaaattc gcgttaaatt tttgttaaat 9900 cagctcattt tttaaccaat aggccgaaat cggcaaaatc ccttataaat caaaagaata 9960 gaccgagata gggttgagtg ttgttccagt ttggaacaag agtccactat taaagaacgt 10020 ggactccaac gtcaaagggc gaaaaaccgt ctatcagggc gatggcccac tacgtgaacc 10080 atcaccctaa tcaagttttt tggggtcgag gtgccgtaaa gcactaaatc ggaaccctaa 10140 agggagcccc cgatttagag cttgacgggg aaagccggcg aacgtggcga gaaaggaagg 10200 gaagaaagcg aaaggagcgg gcgctagggc gctggcaagt gtagcggtca cgctgcgcgt 10260 aaccaccaca cccgccgcgc ttaatgcgcc gctacagggc gcgtcccatt cgccattcag 10320 gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac gccagctggc 10380 gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt cccagtcacg 10440 acgttgtaaa acgacggcca gtgagcgcgc ggcgaattgg gtaccgggcc ccc 10493 <210> 20 <211> 10491 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 20 cctcgagggc tagccattct ccctatcagt gatagagatc tatttaagcc cgagtgagca 60 cgcagtccct atcagtgata gagaggtctc cattttgaag cgggaggttt gaacgcgcag 120 ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt gacgagcatc 180 tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg gagttgccgc 240 cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg gccgagaagc 300 tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag gctcttttct 360 ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg gaaaccaccg 420 gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa ctgattcaga 480 gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca aagaccagaa 540 atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat tacttgctcc 600 ccaaaaccca gcctgagctc caatgggcat ggaccaacat ggaacagtac ctcagcgcct 660 gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac gtgtcgcaga 720 cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg atcagatcaa 780 aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg attacctcgg 840 agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg gcctccaact 900 cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc ctgactaaaa 960 ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc aatcggattt 1020 ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc tttctgggat 1080 gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct gcaactaccg 1140 ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg tgcgtaaact 1200 ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc tggtgggagg 1260 aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctcgga ggaagcaagg 1320 tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc gtgatcgtca 1380 cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc gaacaccagc 1440 agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat catgactttg 1500 ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat cacgtggttg 1560 aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc gcccccagtg 1620 acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca tcgacgtcag 1680 acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct cgtcacgtgg 1740 gcatgaatct gatgctgttt ccctgcagac aatgcgagag aatgaatcag aattcaaata 1800 tctgcttcac tcacggacag aaagactgtt tagagtgctt tcccgtgtca gaatctcaac 1860 ccgtttctgt cgtcaaaaag gcgtatcaga aactgtgcta cattcatcat atcatgggaa 1920 aggtgccaga cgcttgcact gcctgcgatc tggtcaatgt ggatttggat gactgcatct 1980 ttgaacaata aatgatttaa atcaggtatg gctgccgatg gttatcttcc agattggctc 2040 gaggacaacc tctctgaggg cattcgcgag tggtgggact tgaaacctgg agccccgaaa 2100 cccaaagcca accagcaaaa gcaggacgac ggccggggtc tggtgcttcc tggctacaag 2160 tacctcggac ccttcaacgg actcgacaag ggggagcccg tcaacgcggc ggacgcagcg 2220 gccctcgagc acgacaaggc ctacgaccag cagctcaaag cgggtgacaa tccgtacctg 2280 cggtataacc acgccgacgc cgagtttcag gagcgtctgc aagaagatac gtcttttggg 2340 ggcaacctcg ggcgagcagt cttccaggcc aagaagcggg ttctcgaacc tctcggtctg 2400 gttgaggaag gcgctaagac ggctcctgga aagaagagac cggtagagca atcaccccag 2460 gaaccagact cctcttcggg catcggcaag aaaggccagc agcccgcgag aaagagactc 2520 aactttgggc agactggcga ctcagagtca gtgcccgacc ctcaaccact cggagaaccc 2580 cccgcagccc cctctggtgt gggatctaat acaatggctg caggcggtgg cgctccaatg 2640 gcagacaata acgaaggcgc cgacggagtg ggtaacgcct caggaaattg gcattgcgat 2700 tccacatggc tgggcgacag agtcatcacc accagcaccc gaacctgggc cctccccacc 2760 tacaacaacc acctctacaa gcaaatctcc agccaatcgg gaggcagcac caacgacaac 2820 acctacttcg gctacagcac cccctggggg tattttgact ttaacagatt ccactgccac 2880 ttctcaccac gtgactggca gcgactcatc aacaacaact ggggattccg gcccaagaag 2940 ctcaacttca agctcttcaa catccaggtc aaggaggtca cgacgaatga tggcaccacg 3000 accatcgcca ataaccttac cagcacggtt caggtcttta cggactcgga ataccagctc 3060 ccgtacgtcc tcggctctgc gcaccagggc tgcctgcctc cgttcccggc ggacgtcttc 3120 atgattcctc agtacgggta cctgactctg aacaatggca gtcaggccgt gggccgttcc 3180 tccttctact gcctggaata ctttccttct caaatgctga gaacgggcaa caactttcag 3240 ttcagctaca cgtttgagga cgtgcctttt cacagcagct acgcgcacag ccaaagcctg 3300 gaccggctga tgaaccccct catcgaccag tacctgtact acctgtctcg gactcagacc 3360 acgagtggta ccgcaggaaa tcggacgttg caattttctc aggccgggcc tagtagcatg 3420 gcgaatcagg ccaaaaactg gctacccggg ccctgctacc ggcagcaacg cgtctccaag 3480 acaaccaatc aaaataacaa cagcaacttt gcctggaccg gtgccaccaa gtatcatctg 3540 aatggcagag actctctggt aaatcccggt cccgctatgg caacccacaa ggacgacgaa 3600 gacaaatttt ttccgatgag cggagtctta atatttggga aacagggagc tggaaatagc 3660 aacgtggacc ttgacaacgt tatgataacc aacgaggaag aaattaaaac caccaaccca 3720 gtggccacag aagagtacgg cacggtggcc actaacctgc aatcggccaa caccgctcct 3780 gctacaggga ccgtcaacag tcaaggagcc ttacctggca tggtctggca ggaccgggac 3840 gtgtacctgc agggtcctat ctgggccaag attcctcaca cggacggaca ctttcatccc 3900 tcgccgctga tgggaggctt tggactgaaa cacccgcctc ctcagatcct gattaagaat 3960 acacctgttc ccgcgaatcc tccaactacc ttcagtccag ctaagtttgc gtcgttcatc 4020 acgcagtaca gcaccggaca ggtcagcgtg gaaattgaat gggagctgca gaaagaaaac 4080 agcaaacgct ggaacccaga gattcaatac acttccaact acaacaaatc tacaaatgtg 4140 gactttgctg ttgacacaaa tggcgtttat tctgagcctc gccccatcgg cacccgttac 4200 ctcacccgta atctgtaaac tagtttgctt gttaatcaat aaaccgttta attcgtttca 4260 gttgaacttt ggtctctgcg tatttctttc ttatctagtt tccatgctct agaggtcctg 4320 tattagaggt cacgtgagtg ttttgcgaca ttttgcgaca ccatgtggtc acgctgggta 4380 tttaagcccg agtgagcacg cagggtctcc attttgaagc gggaggtttg aacgcgcagc 4440 cgccaagccg aattctgcag atatcggggt tggggttgcg ccttttccaa ggcagccctg 4500 ggtttgcgca gggacgcggc tgctctgggc gtggttccgg gaaacgcagc ggcgccgacc 4560 ctgggtctcg cacattcttc acgtccgttc gcagcgtcac ccggatcttc gccgctaccc 4620 ttgtgggccc cccggcgacg cttcctgctc cgcccctaag tcgggaaggt tccttgcggt 4680 tcgcggcgtg ccggacgtga caaacggaag ccgcacgtct cactagtacc ctcgcagacg 4740 gacagcgcca gggagcaatg gcagcgcgcc gaccgcgatg ggctgtggcc aatagcggct 4800 gctcagcagg gcgcgccgag agcagcggcc gggaaggggc ggtgcgggag gcggggtgtg 4860 gggcggtagt gtgggccctg ttcctgcccg cgcggtgttc cgcattctgc aagcctccgg 4920 agcgcacgtc ggcagtcggc tccctcgttg accgaatcac cgacctctct ccccagaagc 4980 tcccgggagc ttgtatatcc attttcggat ctgatcagca cgtgttgaca attaatcatc 5040 ggcatagtat atcggcatag tataatacga caaggtgagg aacgccacca tggccaagcc 5100 tttgtctcaa gaagaatcca ccctcattga aagagcaacg gctacaatca acagcatccc 5160 catctctgaa gactacagcg tcgccagcgc agctctctct agcgacggcc gcatcttcac 5220 tggtgtcaat gtatatcatt ttactggggg accttgtgca gaactcgtgg tgctgggcac 5280 tgctgctgct gcggcagctg gcaacctgac ttgtatcgtc gcgatcggaa atgagaacag 5340 gggcatcttg agcccctgcg gacggtgccg acaggtgctt ctcgatctgc atcctgggat 5400 caaagccata gtgaaggaca gtgatggaca gccgacggca gttgggattc gtgaattgct 5460 gccctctggt tatgtgtggg agggctaagc acttcgtggc cgaggagcag gactgacacg 5520 tgctacgaga tttcgattcc accgccgcct tctatgaaag gttgggcttc ggaatcgttt 5580 tccgggacgc cggctggatg atcctccagc gcggggatct catgctggag ttcttcgccc 5640 accccaactt gtttattgca gcttataatg gttacaaata aagcaatagc atcacaaatt 5700 tcacaaataa agcatttttt tcactgcatt ctagttgtgg tttgtccaaa ctcatcaatg 5760 tatcttagcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat 5820 gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctctcct aggccagaaa 5880 tggcgccgga ggcgggaaca aggtggtgga tgagtgctac atccccaatt acttgctccc 5940 caaaacccag cctgagtccc tatcagtgat agagactcca gtgggcgtgg actaatatgg 6000 aacagtattt aagcgcctgt ccctatcagt gatagagatt tgaatctcac ggagcgtaaa 6060 cggttggtgg cgcagcatct gtttaaacgc agacgcagga gcagaacaaa gagaatcaga 6120 atcccaattc tgatgcgccg gtgatcagat caaaaacttc agccaggtac atggagctgg 6180 tcgggtggct cgtggacaag gggattacct cggagaagca gtggattcag gaggaccagg 6240 cctcatacat ctccttcaat gcggcctcca actcgcggtc ccaaatcaag gctgccttgg 6300 acaatgcggg aaagattatg agcctgacta aaaccgcccc cgactacctg gtgggccagc 6360 agcccgtgga ggacatttcc agcaatcgga tttataaaat tttggaacta aacgggtacg 6420 atccccaata tgcggcttcc gtctttctgg gatgggccac gaaaaagttc ggcaagagga 6480 acaccatctg gctgtttggg cctgcaacta ccgggaagac caacatcgcg gaggccatag 6540 cccacactgt gcccttctac gggtgcgtaa actggaccaa tgagaacttt cccttcaacg 6600 actgtgtcga caagatggtg atctggtggg aggaggggaa gatgaccgcc aaggtcgtgg 6660 agtcggccaa agccattctc ggaggaagca aggtgcgcgt ggaccagaaa tgcaagtcct 6720 cggcccagat agacccgact cccgtgatcg tcacctccaa caccaacatg tgcgccgtga 6780 ttgacgggaa ctcaacgacc ttcgaacacc agcagccgtt gcaagaccgg atgttcaaat 6840 ttgaactcac ccgccgtctg gatcatgact ttgggaaggt caccaagcag gaagtcaaag 6900 actttttccg gtgggcaaag gatcacgtgg ttgaggtgga gcatgaattc tacgtcaaaa 6960 agggtggagc caagaaaaga cccgccccca gtgacgcaga tataagtgag cccaaacggg 7020 tgcgcgagtc agttgcgcag ccatcgacgt cagacgcgga agcttcgatc aactacgcag 7080 acaggtacca aaacaaatgt tctcgtcacg tgggcatgaa tctgatgctg tttccctgca 7140 gacaatgcga gagaatgaat cagaattcaa atatctgctt cactcacgga cagaaagact 7200 gtttagagtg ctttcccgtg tcagaatctc aacccgtttc tgtcgtcaaa aaggcgtatc 7260 agaaactgtg ctacattcat catatcatgg gaaaggtgcc agacgcttgc actgcctgcg 7320 atctggtcaa tgtggatttg gatgactgca tctttgaaca ataaactagt ttgcttgtta 7380 atcaataaac cgtttaattc gtttcagttg aactttggtc tctgcgtatt tctttcttat 7440 ctagtttcca tgctctagag tatacgatat ccatcacact ggcggccgct cgactagagc 7500 ggccgccacc gcggtggagc tccagctttt gttcgcgcgc ttggcgtaat catggtcata 7560 gctgtttcct gtgtgaaatt ccacagcctg gggtgcctaa ttgcgttgcg ctcactgccc 7620 gctttccagt cgggaaacct gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg 7680 agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg 7740 gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg cggtaatacg gttatccaca 7800 gaatcagggg ataacgcagg aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac 7860 cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc gcccccctga cgagcatcac 7920 aaaaatcgac gctcaagtca gaggtggcga aacccgacag gactataaag ataccaggcg 7980 tttccccctg gaagctccct cgtgcgctct cctgttccga ccctgccgct taccggatac 8040 ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc atagctcacg ctgtaggtat 8100 ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag 8160 cccgaccgct gcgccttatc cggtaactat cgtcttgagt ccaacccggt aagacacgac 8220 ttatcgccac tggcagcagc cactggtaac aggattagca gagcgaggta tgtaggcggt 8280 gctacagagt tcttgaagtg gtggcctaac tacggctaca ctagaagaac agtatttggt 8340 atctgcgctc tgctgaagcc agttaccttc ggaaaaagag ttggtagctc ttgatccggc 8400 aaacaaacca ccgctggtag cggtggtttt tttgtttgca agcagcagat tacgcgcaga 8460 aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc tcagtggaac 8520 gaaaactcac gttaagggat tttggtcatg agattatcaa aaaggatctt cacctagatc 8580 cttttaaatt aaaaatgaag ttttaaatca atctaaagta tatatgagta aacttggtct 8640 gacagaaata ataaaaaagc cggattaata atctggcttt ttatattctc tctctagtat 8700 ataaacgcag aaaggcccac ccgaaggtga gccagtgtga ctctagtatt attagaaaaa 8760 ctcatcgagc atcaaatgaa actgcaattt attcatatca ggattatcaa taccatattt 8820 ttgaaaaagc cgtttctgta atgaaggaga aaactcaccg aggcagttcc aaagaatggc 8880 aaggtcctgg taacggtctg cgattccgac ccgtccaaca tcaatacaac ctattaattt 8940 cccctcgtca aaaataaggt tatcaagtga gaaatcacca tgagtgacga ctgaatccgg 9000 tgagaatggc aagagcttgt gcatttcttt ccagacttgt tcaacaggcc agccattacg 9060 ctcgtcatca aaatcactcg catcaaccaa accgttattc atgcgtgatt gcgcctgagc 9120 aagacgaaat acacgatcgc tgttaaaagg acaattacaa acaggaatcg aatgtaaccg 9180 gcgcaggaac acggccagcg catcaacaat attttcacct gaatcaggat attcttctaa 9240 tacctggaag gctgttttcc caggaatcgc ggtggtgagt aaccacgcat catcaggagt 9300 acggataaaa tgcttgatgg tcgggagagg cataaactcc gtcagccagt tgagacggac 9360 catctcatct gtaacatcat tggcaacgct acctttgcca tgtttcagaa acaactctgg 9420 cgcatcgggc ttcccataca agcgatagat tgtcgcacct gattgcccga cattatcgcg 9480 agcccattta tacccatata aatcagcgtc catgttggag tttaagcgcg gacgggagca 9540 agacgtttcc cgttgaatat ggctcataac accccttgta ttactgttta tgtaagcaga 9600 cagttttatt gttcatgatg atatattttt atcttgtgca atgtaacatc agagattttg 9660 agacacaacg tggctttgtt gaataaatcg aacttttgct gagttgaagg atcagctcta 9720 gtaaaataat aaaaaagccg gattaataat ctggcttttt atattctctc tctagtatat 9780 aaacgcagaa aggcccaccc gaaggtgagc cagtgtgacg gcacatttcc ccgaaaagtg 9840 ccacctaaat tgtaagcgtt aatattttgt taaaattcgc gttaaatttt tgttaaatca 9900 gctcattttt taaccaatag gccgaaatcg gcaaaatccc ttataaatca aaagaataga 9960 ccgagatagg gttgagtgtt gttccagttt ggaacaagag tccactatta aagaacgtgg 10020 actccaacgt caaagggcga aaaaccgtct atcagggcga tggcccacta cgtgaaccat 10080 caccctaatc aagttttttg gggtcgaggt gccgtaaagc actaaatcgg aaccctaaag 10140 ggagcccccg atttagagct tgacggggaa agccggcgaa cgtggcgaga aaggaaggga 10200 agaaagcgaa aggagcgggc gctagggcgc tggcaagtgt agcggtcacg ctgcgcgtaa 10260 ccaccacacc cgccgcgctt aatgcgccgc tacagggcgc gtcccattcg ccattcaggc 10320 tgcgcaactg ttgggaaggg cgatcggtgc gggcctcttc gctattacgc cagctggcga 10380 aagggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc cagtcacgac 10440 gttgtaaaac gacggccagt gagcgcgcgg cgaattgggt accgggcccc c 10491 <210> 21 <211> 10495 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 21 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatct ccctatcagt 60 gatagagatc gcccgagtga gcacgcaggg tctccatttt gaagcgggag gtttgaacgc 120 gcagccgcca tgccggggtt ttacgagatt gtgattaagg tccccagcga ccttgacgag 180 catctgcccg gcatttctga cagctttgtg aactgggtgg ccgagaagga atgggagttg 240 ccgccagatt ctgacatgga tctgaatctg attgagcagg cacccctgac cgtggccgag 300 aagctgcagc gcgactttct gacggaatgg cgccgtgtga gtaaggcccc ggaggctctt 360 ttctttgtgc aatttgagaa gggagagagc tacttccaca tgcacgtgct cgtggaaacc 420 accggggtga aatccatggt tttgggacgt ttcctgagtc agattcgcga aaaactgatt 480 cagagaattt accgcgggat cgagccgact ttgccaaact ggttcgcggt cacaaagacc 540 agaaatggcg ccggaggcgg gaacaaggtg gtggatgagt gctacatccc caattacttg 600 ctccccaaaa cccagcctga gctccaatgg gcatggacca acatggaaca gtacctcagc 660 gcctgtttga atctcacgga gcgtaaacgg ttggtggcgc agcatctgac gcacgtgtcg 720 cagacgcagg agcagaacaa agagaatcag aatcccaatt ctgatgcgcc ggtgatcaga 780 tcaaaaactt cagccaggta catggagctg gtcgggtggc tcgtggacaa ggggattacc 840 tcggagaagc agtggatcca ggaggaccag gcctcataca tctccttcaa tgcggcctcc 900 aactcgcggt cccaaatcaa ggctgccttg gacaatgcgg gaaagattat gagcctgact 960 aaaaccgccc ccgactacct ggtgggccag cagcccgtgg aggacatttc cagcaatcgg 1020 atttataaaa ttttggaact aaacgggtac gatccccaat atgcggcttc cgtctttctg 1080 ggatgggcca cgaaaaagtt cggcaagagg aacaccatct ggctgtttgg gcctgcaact 1140 accgggaaga ccaacatcgc ggaggccata gcccacactg tgcccttcta cgggtgcgta 1200 aactggacca atgagaactt tcccttcaac gactgtgtcg acaagatggt gatctggtgg 1260 gaggagggga agatgaccgc caaggtcgtg gagtcggcca aagccattct cggaggaagc 1320 aaggtgcgcg tggaccagaa atgcaagtcc tcggcccaga tagacccgac tcccgtgatc 1380 gtcacctcca acaccaacat gtgcgccgtg attgacggga actcaacgac cttcgaacac 1440 cagcagccgt tgcaagaccg gatgttcaaa tttgaactca cccgccgtct ggatcatgac 1500 tttgggaagg tcaccaagca ggaagtcaaa gactttttcc ggtgggcaaa ggatcacgtg 1560 gttgaggtgg agcatgaatt ctacgtcaaa aagggtggag ccaagaaaag acccgccccc 1620 agtgacgcag atataagtga gcccaaacgg gtgcgcgagt cagttgcgca gccatcgacg 1680 tcagacgcgg aagcttcgat caactacgca gacaggtacc aaaacaaatg ttctcgtcac 1740 gtgggcatga atctgatgct gtttccctgc agacaatgcg agagaatgaa tcagaattca 1800 aatatctgct tcactcacgg acagaaagac tgtttagagt gctttcccgt gtcagaatct 1860 caacccgttt ctgtcgtcaa aaaggcgtat cagaaactgt gctacattca tcatatcatg 1920 ggaaaggtgc cagacgcttg cactgcctgc gatctggtca atgtggattt ggatgactgc 1980 atctttgaac aataaatgat ttaaatcagg tatggctgcc gatggttatc ttccagattg 2040 gctcgaggac aacctctctg agggcattcg cgagtggtgg gacttgaaac ctggagcccc 2100 gaaacccaaa gccaaccagc aaaagcagga cgacggccgg ggtctggtgc ttcctggcta 2160 caagtacctc ggacccttca acggactcga caagggggag cccgtcaacg cggcggacgc 2220 agcggccctc gagcacgaca aggcctacga ccagcagctc aaagcgggtg acaatccgta 2280 cctgcggtat aaccacgccg acgccgagtt tcaggagcgt ctgcaagaag atacgtcttt 2340 tgggggcaac ctcgggcgag cagtcttcca ggccaagaag cgggttctcg aacctctcgg 2400 tctggttgag gaaggcgcta agacggctcc tggaaagaag agaccggtag agcaatcacc 2460 ccaggaacca gactcctctt cgggcatcgg caagaaaggc cagcagcccg cgagaaagag 2520 actcaacttt gggcagactg gcgactcaga gtcagtgccc gaccctcaac cactcggaga 2580 accccccgca gccccctctg gtgtgggatc taatacaatg gctgcaggcg gtggcgctcc 2640 aatggcagac aataacgaag gcgccgacgg agtgggtaac gcctcaggaa attggcattg 2700 cgattccaca tggctgggcg acagagtcat caccaccagc acccgaacct gggccctccc 2760 cacctacaac aaccacctct acaagcaaat ctccagccaa tcgggaggca gcaccaacga 2820 caacacctac ttcggctaca gcaccccctg ggggtatttt gactttaaca gattccactg 2880 ccacttctca ccacgtgact ggcagcgact catcaacaac aactggggat tccggcccaa 2940 gaagctcaac ttcaagctct tcaacatcca ggtcaaggag gtcacgacga atgatggcac 3000 cacgaccatc gccaataacc ttaccagcac ggttcaggtc tttacggact cggaatacca 3060 gctcccgtac gtcctcggct ctgcgcacca gggctgcctg cctccgttcc cggcggacgt 3120 cttcatgatt cctcagtacg ggtacctgac tctgaacaat ggcagtcagg ccgtgggccg 3180 ttcctccttc tactgcctgg aatactttcc ttctcaaatg ctgagaacgg gcaacaactt 3240 tcagttcagc tacacgtttg aggacgtgcc ttttcacagc agctacgcgc acagccaaag 3300 cctggaccgg ctgatgaacc ccctcatcga ccagtacctg tactacctgt ctcggactca 3360 gaccacgagt ggtaccgcag gaaatcggac gttgcaattt tctcaggccg ggcctagtag 3420 catggcgaat caggccaaaa actggctacc cgggccctgc taccggcagc aacgcgtctc 3480 caagacaacc aatcaaaata acaacagcaa ctttgcctgg accggtgcca ccaagtatca 3540 tctgaatggc agagactctc tggtaaatcc cggtcccgct atggcaaccc acaaggacga 3600 cgaagacaaa ttttttccga tgagcggagt cttaatattt gggaaacagg gagctggaaa 3660 tagcaacgtg gaccttgaca acgttatgat aaccaacgag gaagaaatta aaaccaccaa 3720 cccagtggcc acagaagagt acggcacggt ggccactaac ctgcaatcgg ccaacaccgc 3780 tcctgctaca gggaccgtca acagtcaagg agccttacct ggcatggtct ggcaggaccg 3840 ggacgtgtac ctgcagggtc ctatctgggc caagattcct cacacggacg gacactttca 3900 tccctcgccg ctgatgggag gctttggact gaaacacccg cctcctcaga tcctgattaa 3960 gaatacacct gttcccgcga atcctccaac taccttcagt ccagctaagt ttgcgtcgtt 4020 catcacgcag tacagcaccg gacaggtcag cgtggaaatt gaatgggagc tgcagaaaga 4080 aaacagcaaa cgctggaacc cagagattca atacacttcc aactacaaca aatctacaaa 4140 tgtggacttt gctgttgaca caaatggcgt ttattctgag cctcgcccca tcggcacccg 4200 ttacctcacc cgtaatctgt aaactagttt gcttgttaat caataaaccg tttaattcgt 4260 ttcagttgaa ctttggtctc tgcgtatttc tttcttatct agtttccatg ctctagaggt 4320 cctgtattag aggtcacgtg agtgttttgc gacattttgc gacaccatgt ggtcacgctg 4380 ggtatttaag cccgagtgag cacgcagggt ctccattttg aagcgggagg tttgaacgcg 4440 cagccgccaa gccgaattct gcagatatcg gggttggggt tgcgcctttt ccaaggcagc 4500 cctgggtttg cgcagggacg cggctgctct gggcgtggtt ccgggaaacg cagcggcgcc 4560 gaccctgggt ctcgcacatt cttcacgtcc gttcgcagcg tcacccggat cttcgccgct 4620 acccttgtgg gccccccggc gacgcttcct gctccgcccc taagtcggga aggttccttg 4680 cggttcgcgg cgtgccggac gtgacaaacg gaagccgcac gtctcactag taccctcgca 4740 gacggacagc gccagggagc aatggcagcg cgccgaccgc gatgggctgt ggccaatagc 4800 ggctgctcag cagggcgcgc cgagagcagc ggccgggaag gggcggtgcg ggaggcgggg 4860 tgtggggcgg tagtgtgggc cctgttcctg cccgcgcggt gttccgcatt ctgcaagcct 4920 ccggagcgca cgtcggcagt cggctccctc gttgaccgaa tcaccgacct ctctccccag 4980 aagctcccgg gagcttgtat atccattttc ggatctgatc agcacgtgtt gacaattaat 5040 catcggcata gtatatcggc atagtataat acgacaaggt gaggaacgcc accatggcca 5100 agcctttgtc tcaagaagaa tccaccctca ttgaaagagc aacggctaca atcaacagca 5160 tccccatctc tgaagactac agcgtcgcca gcgcagctct ctctagcgac ggccgcatct 5220 tcactggtgt caatgtatat cattttactg ggggaccttg tgcagaactc gtggtgctgg 5280 gcactgctgc tgctgcggca gctggcaacc tgacttgtat cgtcgcgatc ggaaatgaga 5340 acaggggcat cttgagcccc tgcggacggt gccgacaggt gcttctcgat ctgcatcctg 5400 ggatcaaagc catagtgaag gacagtgatg gacagccgac ggcagttggg attcgtgaat 5460 tgctgccctc tggttatgtg tgggagggct aagcacttcg tggccgagga gcaggactga 5520 cacgtgctac gagatttcga ttccaccgcc gccttctatg aaaggttggg cttcggaatc 5580 gttttccggg acgccggctg gatgatcctc cagcgcgggg atctcatgct ggagttcttc 5640 gcccacccca acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 5700 aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 5760 aatgtatctt agcgctcact gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat 5820 taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc tcctaggcca 5880 gaaatggcgc cggaggcggg aacaaggtgg tggatgagtg ctacatcccc aattacttgc 5940 tccccaaaac ccagcctgag ctccagtggg cgtggactaa tatggaatcc ctatcagtga 6000 tagagacagt atttaagcgc ctgtccctat cagtgataga gatttgaatc tcacggagcg 6060 taaacggttg gtggcgcagc atctgtttaa acgcagacgc aggagcagaa caaagagaat 6120 cagaatccca attctgatgc gccggtgatc agatcaaaaa cttcagccag gtacatggag 6180 ctggtcgggt ggctcgtgga caaggggatt acctcggaga agcagtggat tcaggaggac 6240 caggcctcat acatctcctt caatgcggcc tccaactcgc ggtcccaaat caaggctgcc 6300 ttggacaatg cgggaaagat tatgagcctg actaaaaccg cccccgacta cctggtgggc 6360 cagcagcccg tggaggacat ttccagcaat cggatttata aaattttgga actaaacggg 6420 tacgatcccc aatatgcggc ttccgtcttt ctgggatggg ccacgaaaaa gttcggcaag 6480 aggaacacca tctggctgtt tgggcctgca actaccggga agaccaacat cgcggaggcc 6540 atagcccaca ctgtgccctt ctacgggtgc gtaaactgga ccaatgagaa ctttcccttc 6600 aacgactgtg tcgacaagat ggtgatctgg tgggaggagg ggaagatgac cgccaaggtc 6660 gtggagtcgg ccaaagccat tctcggagga agcaaggtgc gcgtggacca gaaatgcaag 6720 tcctcggccc agatagaccc gactcccgtg atcgtcacct ccaacaccaa catgtgcgcc 6780 gtgattgacg ggaactcaac gaccttcgaa caccagcagc cgttgcaaga ccggatgttc 6840 aaatttgaac tcacccgccg tctggatcat gactttggga aggtcaccaa gcaggaagtc 6900 aaagactttt tccggtgggc aaaggatcac gtggttgagg tggagcatga attctacgtc 6960 aaaaagggtg gagccaagaa aagacccgcc cccagtgacg cagatataag tgagcccaaa 7020 cgggtgcgcg agtcagttgc gcagccatcg acgtcagacg cggaagcttc gatcaactac 7080 gcagacaggt accaaaacaa atgttctcgt cacgtgggca tgaatctgat gctgtttccc 7140 tgcagacaat gcgagagaat gaatcagaat tcaaatatct gcttcactca cggacagaaa 7200 gactgtttag agtgctttcc cgtgtcagaa tctcaacccg tttctgtcgt caaaaaggcg 7260 tatcagaaac tgtgctacat tcatcatatc atgggaaagg tgccagacgc ttgcactgcc 7320 tgcgatctgg tcaatgtgga tttggatgac tgcatctttg aacaataaac tagtttgctt 7380 gttaatcaat aaaccgttta attcgtttca gttgaacttt ggtctctgcg tatttctttc 7440 ttatctagtt tccatgctct agagtatacg atatccatca cactggcggc cgctcgacta 7500 gagcggccgc caccgcggtg gagctccagc ttttgttcgc gcgcttggcg taatcatggt 7560 catagctgtt tcctgtgtga aattccacag cctggggtgc ctaattgcgt tgcgctcact 7620 gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc 7680 ggggagaggc ggtttgcgta ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg 7740 ctcggtcgtt cggctgcggc gagcggtatc agctcactca aaggcggtaa tacggttatc 7800 cacagaatca ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag 7860 gaaccgtaaa aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca 7920 tcacaaaaat cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca 7980 ggcgtttccc cctggaagct ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg 8040 atacctgtcc gcctttctcc cttcgggaag cgtggcgctt tctcatagct cacgctgtag 8100 gtatctcagt tcggtgtagg tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt 8160 tcagcccgac cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc cggtaagaca 8220 cgacttatcg ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg 8280 cggtgctaca gagttcttga agtggtggcc taactacggc tacactagaa gaacagtatt 8340 tggtatctgc gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc 8400 cggcaaacaa accaccgctg gtagcggtgg tttttttgtt tgcaagcagc agattacgcg 8460 cagaaaaaaa ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg 8520 gaacgaaaac tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta 8580 gatcctttta aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg 8640 gtctgacaga aataataaaa aagccggatt aataatctgg ctttttatat tctctctcta 8700 gtatataaac gcagaaaggc ccacccgaag gtgagccagt gtgactctag tattattaga 8760 aaaactcatc gagcatcaaa tgaaactgca atttattcat atcaggatta tcaataccat 8820 atttttgaaa aagccgtttc tgtaatgaag gagaaaactc accgaggcag ttccaaagaa 8880 tggcaaggtc ctggtaacgg tctgcgattc cgacccgtcc aacatcaata caacctatta 8940 atttcccctc gtcaaaaata aggttatcaa gtgagaaatc accatgagtg acgactgaat 9000 ccggtgagaa tggcaagagc ttgtgcattt ctttccagac ttgttcaaca ggccagccat 9060 tacgctcgtc atcaaaatca ctcgcatcaa ccaaaccgtt attcatgcgt gattgcgcct 9120 gagcaagacg aaatacacga tcgctgttaa aaggacaatt acaaacagga atcgaatgta 9180 accggcgcag gaacacggcc agcgcatcaa caatattttc acctgaatca ggatattctt 9240 ctaatacctg gaaggctgtt ttcccaggaa tcgcggtggt gagtaaccac gcatcatcag 9300 gagtacggat aaaatgcttg atggtcggga gaggcataaa ctccgtcagc cagttgagac 9360 ggaccatctc atctgtaaca tcattggcaa cgctaccttt gccatgtttc agaaacaact 9420 ctggcgcatc gggcttccca tacaagcgat agattgtcgc acctgattgc ccgacattat 9480 cgcgagccca tttataccca tataaatcag cgtccatgtt ggagtttaag cgcggacggg 9540 agcaagacgt ttcccgttga atatggctca taacacccct tgtattactg tttatgtaag 9600 cagacagttt tattgttcat gatgatatat ttttatcttg tgcaatgtaa catcagagat 9660 tttgagacac aacgtggctt tgttgaataa atcgaacttt tgctgagttg aaggatcagc 9720 tctagtaaaa taataaaaaa gccggattaa taatctggct ttttatattc tctctctagt 9780 atataaacgc agaaaggccc acccgaaggt gagccagtgt gacggcacat ttccccgaaa 9840 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 9900 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 9960 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 10020 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 10080 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 10140 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 10200 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 10260 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 10320 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 10380 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 10440 cgacgttgta aaacgacggc cagtgagcgc gcggcgaatt gggtaccggg ccccc 10495 <210> 22 <211> 10493 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 22 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatcg cccgagtgag 60 cacgcagggt ctccattttg atccctatca gtgatagaga agcgggaggt ttgaacgcgc 120 agccgccatg ccggggtttt acgagattgt gattaaggtc cccagcgacc ttgacgagca 180 tctgcccggc atttctgaca gctttgtgaa ctgggtggcc gagaaggaat gggagttgcc 240 gccagattct gacatggatc tgaatctgat tgagcaggca cccctgaccg tggccgagaa 300 gctgcagcgc gactttctga cggaatggcg ccgtgtgagt aaggccccgg aggctctttt 360 ctttgtgcaa tttgagaagg gagagagcta cttccacatg cacgtgctcg tggaaaccac 420 cggggtgaaa tccatggttt tgggacgttt cctgagtcag attcgcgaaa aactgattca 480 gagaatttac cgcgggatcg agccgacttt gccaaactgg ttcgcggtca caaagaccag 540 aaatggcgcc ggaggcggga acaaggtggt ggatgagtgc tacatcccca attacttgct 600 ccccaaaacc cagcctgagc tccaatgggc atggaccaac atggaacagt acctcagcgc 660 ctgtttgaat ctcacggagc gtaaacggtt ggtggcgcag catctgacgc acgtgtcgca 720 gacgcaggag cagaacaaag agaatcagaa tcccaattct gatgcgccgg tgatcagatc 780 aaaaacttca gccaggtaca tggagctggt cgggtggctc gtggacaagg ggattacctc 840 ggagaagcag tggatccagg aggaccaggc ctcatacatc tccttcaatg cggcctccaa 900 ctcgcggtcc caaatcaagg ctgccttgga caatgcggga aagattatga gcctgactaa 960 aaccgccccc gactacctgg tgggccagca gcccgtggag gacatttcca gcaatcggat 1020 ttataaaatt ttggaactaa acgggtacga tccccaatat gcggcttccg tctttctggg 1080 atgggccacg aaaaagttcg gcaagaggaa caccatctgg ctgtttgggc ctgcaactac 1140 cgggaagacc aacatcgcgg aggccatagc ccacactgtg cccttctacg ggtgcgtaaa 1200 ctggaccaat gagaactttc ccttcaacga ctgtgtcgac aagatggtga tctggtggga 1260 ggaggggaag atgaccgcca aggtcgtgga gtcggccaaa gccattctcg gaggaagcaa 1320 ggtgcgcgtg gaccagaaat gcaagtcctc ggcccagata gacccgactc ccgtgatcgt 1380 cacctccaac accaacatgt gcgccgtgat tgacgggaac tcaacgacct tcgaacacca 1440 gcagccgttg caagaccgga tgttcaaatt tgaactcacc cgccgtctgg atcatgactt 1500 tgggaaggtc accaagcagg aagtcaaaga ctttttccgg tgggcaaagg atcacgtggt 1560 tgaggtggag catgaattct acgtcaaaaa gggtggagcc aagaaaagac ccgcccccag 1620 tgacgcagat ataagtgagc ccaaacgggt gcgcgagtca gttgcgcagc catcgacgtc 1680 agacgcggaa gcttcgatca actacgcaga caggtaccaa aacaaatgtt ctcgtcacgt 1740 gggcatgaat ctgatgctgt ttccctgcag acaatgcgag agaatgaatc agaattcaaa 1800 tatctgcttc actcacggac agaaagactg tttagagtgc tttcccgtgt cagaatctca 1860 acccgtttct gtcgtcaaaa aggcgtatca gaaactgtgc tacattcatc atatcatggg 1920 aaaggtgcca gacgcttgca ctgcctgcga tctggtcaat gtggatttgg atgactgcat 1980 ctttgaacaa taaatgattt aaatcaggta tggctgccga tggttatctt ccagattggc 2040 tcgaggacaa cctctctgag ggcattcgcg agtggtggga cttgaaacct ggagccccga 2100 aacccaaagc caaccagcaa aagcaggacg acggccgggg tctggtgctt cctggctaca 2160 agtacctcgg acccttcaac ggactcgaca agggggagcc cgtcaacgcg gcggacgcag 2220 cggccctcga gcacgacaag gcctacgacc agcagctcaa agcgggtgac aatccgtacc 2280 tgcggtataa ccacgccgac gccgagtttc aggagcgtct gcaagaagat acgtcttttg 2340 ggggcaacct cgggcgagca gtcttccagg ccaagaagcg ggttctcgaa cctctcggtc 2400 tggttgagga aggcgctaag acggctcctg gaaagaagag accggtagag caatcacccc 2460 aggaaccaga ctcctcttcg ggcatcggca agaaaggcca gcagcccgcg agaaagagac 2520 tcaactttgg gcagactggc gactcagagt cagtgcccga ccctcaacca ctcggagaac 2580 cccccgcagc cccctctggt gtgggatcta atacaatggc tgcaggcggt ggcgctccaa 2640 tggcagacaa taacgaaggc gccgacggag tgggtaacgc ctcaggaaat tggcattgcg 2700 attccacatg gctgggcgac agagtcatca ccaccagcac ccgaacctgg gccctcccca 2760 cctacaacaa ccacctctac aagcaaatct ccagccaatc gggaggcagc accaacgaca 2820 acacctactt cggctacagc accccctggg ggtattttga ctttaacaga ttccactgcc 2880 acttctcacc acgtgactgg cagcgactca tcaacaacaa ctggggattc cggcccaaga 2940 agctcaactt caagctcttc aacatccagg tcaaggaggt cacgacgaat gatggcacca 3000 cgaccatcgc caataacctt accagcacgg ttcaggtctt tacggactcg gaataccagc 3060 tcccgtacgt cctcggctct gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct 3120 tcatgattcc tcagtacggg tacctgactc tgaacaatgg cagtcaggcc gtgggccgtt 3180 cctccttcta ctgcctggaa tactttcctt ctcaaatgct gagaacgggc aacaactttc 3240 agttcagcta cacgtttgag gacgtgcctt ttcacagcag ctacgcgcac agccaaagcc 3300 tggaccggct gatgaacccc ctcatcgacc agtacctgta ctacctgtct cggactcaga 3360 ccacgagtgg taccgcagga aatcggacgt tgcaattttc tcaggccggg cctagtagca 3420 tggcgaatca ggccaaaaac tggctacccg ggccctgcta ccggcagcaa cgcgtctcca 3480 agacaaccaa tcaaaataac aacagcaact ttgcctggac cggtgccacc aagtatcatc 3540 tgaatggcag agactctctg gtaaatcccg gtcccgctat ggcaacccac aaggacgacg 3600 aagacaaatt ttttccgatg agcggagtct taatatttgg gaaacaggga gctggaaata 3660 gcaacgtgga ccttgacaac gttatgataa ccaacgagga agaaattaaa accaccaacc 3720 cagtggccac agaagagtac ggcacggtgg ccactaacct gcaatcggcc aacaccgctc 3780 ctgctacagg gaccgtcaac agtcaaggag ccttacctgg catggtctgg caggaccggg 3840 acgtgtacct gcagggtcct atctgggcca agattcctca cacggacgga cactttcatc 3900 cctcgccgct gatgggaggc tttggactga aacacccgcc tcctcagatc ctgattaaga 3960 atacacctgt tcccgcgaat cctccaacta ccttcagtcc agctaagttt gcgtcgttca 4020 tcacgcagta cagcaccgga caggtcagcg tggaaattga atgggagctg cagaaagaaa 4080 acagcaaacg ctggaaccca gagattcaat acacttccaa ctacaacaaa tctacaaatg 4140 tggactttgc tgttgacaca aatggcgttt attctgagcc tcgccccatc ggcacccgtt 4200 acctcacccg taatctgtaa actagtttgc ttgttaatca ataaaccgtt taattcgttt 4260 cagttgaact ttggtctctg cgtatttctt tcttatctag tttccatgct ctagaggtcc 4320 tgtattagag gtcacgtgag tgttttgcga cattttgcga caccatgtgg tcacgctggg 4380 tatttaagcc cgagtgagca cgcagggtct ccattttgaa gcgggaggtt tgaacgcgca 4440 gccgccaagc cgaattctgc agatatcggg gttggggttg cgccttttcc aaggcagccc 4500 tgggtttgcg cagggacgcg gctgctctgg gcgtggttcc gggaaacgca gcggcgccga 4560 ccctgggtct cgcacattct tcacgtccgt tcgcagcgtc acccggatct tcgccgctac 4620 ccttgtgggc cccccggcga cgcttcctgc tccgccccta agtcgggaag gttccttgcg 4680 gttcgcggcg tgccggacgt gacaaacgga agccgcacgt ctcactagta ccctcgcaga 4740 cggacagcgc cagggagcaa tggcagcgcg ccgaccgcga tgggctgtgg ccaatagcgg 4800 ctgctcagca gggcgcgccg agagcagcgg ccgggaaggg gcggtgcggg aggcggggtg 4860 tggggcggta gtgtgggccc tgttcctgcc cgcgcggtgt tccgcattct gcaagcctcc 4920 ggagcgcacg tcggcagtcg gctccctcgt tgaccgaatc accgacctct ctccccagaa 4980 gctcccggga gcttgtatat ccattttcgg atctgatcag cacgtgttga caattaatca 5040 tcggcatagt atatcggcat agtataatac gacaaggtga ggaacgccac catggccaag 5100 cctttgtctc aagaagaatc caccctcatt gaaagagcaa cggctacaat caacagcatc 5160 cccatctctg aagactacag cgtcgccagc gcagctctct ctagcgacgg ccgcatcttc 5220 actggtgtca atgtatatca ttttactggg ggaccttgtg cagaactcgt ggtgctgggc 5280 actgctgctg ctgcggcagc tggcaacctg acttgtatcg tcgcgatcgg aaatgagaac 5340 aggggcatct tgagcccctg cggacggtgc cgacaggtgc ttctcgatct gcatcctggg 5400 atcaaagcca tagtgaagga cagtgatgga cagccgacgg cagttgggat tcgtgaattg 5460 ctgccctctg gttatgtgtg ggagggctaa gcacttcgtg gccgaggagc aggactgaca 5520 cgtgctacga gatttcgatt ccaccgccgc cttctatgaa aggttgggct tcggaatcgt 5580 tttccgggac gccggctgga tgatcctcca gcgcggggat ctcatgctgg agttcttcgc 5640 ccaccccaac ttgtttattg cagcttataa tggttacaaa taaagcaata gcatcacaaa 5700 tttcacaaat aaagcatttt tttcactgca ttctagttgt ggtttgtcca aactcatcaa 5760 tgtatcttag cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta 5820 atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctc ctaggccaga 5880 aatggcgccg gaggcgggaa caaggtggtg gatgagtgct acatccccaa ttacttgctc 5940 cccaaaaccc agcctgagct ccagtgggcg tggactaata tggaatccct atcagtgata 6000 gagacagtat ttaagcgcct gtccctatca gtgatagaga tttgaatctc acggagcgta 6060 aacggttggt ggcgcagcat ctgtttaaac gcagacgcag gagcagaaca aagagaatca 6120 gaatcccaat tctgatgcgc cggtgatcag atcaaaaact tcagccaggt acatggagct 6180 ggtcgggtgg ctcgtggaca aggggattac ctcggagaag cagtggattc aggaggacca 6240 ggcctcatac atctccttca atgcggcctc caactcgcgg tcccaaatca aggctgcctt 6300 ggacaatgcg ggaaagatta tgagcctgac taaaaccgcc cccgactacc tggtgggcca 6360 gcagcccgtg gaggacattt ccagcaatcg gatttataaa attttggaac taaacgggta 6420 cgatccccaa tatgcggctt ccgtctttct gggatgggcc acgaaaaagt tcggcaagag 6480 gaacaccatc tggctgtttg ggcctgcaac taccgggaag accaacatcg cggaggccat 6540 agcccacact gtgcccttct acgggtgcgt aaactggacc aatgagaact ttcccttcaa 6600 cgactgtgtc gacaagatgg tgatctggtg ggaggagggg aagatgaccg ccaaggtcgt 6660 ggagtcggcc aaagccattc tcggaggaag caaggtgcgc gtggaccaga aatgcaagtc 6720 ctcggcccag atagacccga ctcccgtgat cgtcacctcc aacaccaaca tgtgcgccgt 6780 gattgacggg aactcaacga ccttcgaaca ccagcagccg ttgcaagacc ggatgttcaa 6840 atttgaactc acccgccgtc tggatcatga ctttgggaag gtcaccaagc aggaagtcaa 6900 agactttttc cggtgggcaa aggatcacgt ggttgaggtg gagcatgaat tctacgtcaa 6960 aaagggtgga gccaagaaaa gacccgcccc cagtgacgca gatataagtg agcccaaacg 7020 ggtgcgcgag tcagttgcgc agccatcgac gtcagacgcg gaagcttcga tcaactacgc 7080 agacaggtac caaaacaaat gttctcgtca cgtgggcatg aatctgatgc tgtttccctg 7140 cagacaatgc gagagaatga atcagaattc aaatatctgc ttcactcacg gacagaaaga 7200 ctgtttagag tgctttcccg tgtcagaatc tcaacccgtt tctgtcgtca aaaaggcgta 7260 tcagaaactg tgctacattc atcatatcat gggaaaggtg ccagacgctt gcactgcctg 7320 cgatctggtc aatgtggatt tggatgactg catctttgaa caataaacta gtttgcttgt 7380 taatcaataa accgtttaat tcgtttcagt tgaactttgg tctctgcgta tttctttctt 7440 atctagtttc catgctctag agtatacgat atccatcaca ctggcggccg ctcgactaga 7500 gcggccgcca ccgcggtgga gctccagctt ttgttcgcgc gcttggcgta atcatggtca 7560 tagctgtttc ctgtgtgaaa ttccacagcc tggggtgcct aattgcgttg cgctcactgc 7620 ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc caacgcgcgg 7680 ggagaggcgg tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct 7740 cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 7800 cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 7860 accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 7920 acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 7980 cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 8040 acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 8100 atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 8160 agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 8220 acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 8280 gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 8340 gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 8400 gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 8460 gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 8520 acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 8580 tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 8640 ctgacagaaa taataaaaaa gccggattaa taatctggct ttttatattc tctctctagt 8700 atataaacgc agaaaggccc acccgaaggt gagccagtgt gactctagta ttattagaaa 8760 aactcatcga gcatcaaatg aaactgcaat ttattcatat caggattatc aataccatat 8820 ttttgaaaaa gccgtttctg taatgaagga gaaaactcac cgaggcagtt ccaaagaatg 8880 gcaaggtcct ggtaacggtc tgcgattccg acccgtccaa catcaataca acctattaat 8940 ttcccctcgt caaaaataag gttatcaagt gagaaatcac catgagtgac gactgaatcc 9000 ggtgagaatg gcaagagctt gtgcatttct ttccagactt gttcaacagg ccagccatta 9060 cgctcgtcat caaaatcact cgcatcaacc aaaccgttat tcatgcgtga ttgcgcctga 9120 gcaagacgaa atacacgatc gctgttaaaa ggacaattac aaacaggaat cgaatgtaac 9180 cggcgcagga acacggccag cgcatcaaca atattttcac ctgaatcagg atattcttct 9240 aatacctgga aggctgtttt cccaggaatc gcggtggtga gtaaccacgc atcatcagga 9300 gtacggataa aatgcttgat ggtcgggaga ggcataaact ccgtcagcca gttgagacgg 9360 accatctcat ctgtaacatc attggcaacg ctacctttgc catgtttcag aaacaactct 9420 ggcgcatcgg gcttcccata caagcgatag attgtcgcac ctgattgccc gacattatcg 9480 cgagcccatt tatacccata taaatcagcg tccatgttgg agtttaagcg cggacgggag 9540 caagacgttt cccgttgaat atggctcata acaccccttg tattactgtt tatgtaagca 9600 gacagtttta ttgttcatga tgatatattt ttatcttgtg caatgtaaca tcagagattt 9660 tgagacacaa cgtggctttg ttgaataaat cgaacttttg ctgagttgaa ggatcagctc 9720 tagtaaaata ataaaaaagc cggattaata atctggcttt ttatattctc tctctagtat 9780 ataaacgcag aaaggcccac ccgaaggtga gccagtgtga cggcacattt ccccgaaaag 9840 tgccacctaa attgtaagcg ttaatatttt gttaaaattc gcgttaaatt tttgttaaat 9900 cagctcattt tttaaccaat aggccgaaat cggcaaaatc ccttataaat caaaagaata 9960 gaccgagata gggttgagtg ttgttccagt ttggaacaag agtccactat taaagaacgt 10020 ggactccaac gtcaaagggc gaaaaaccgt ctatcagggc gatggcccac tacgtgaacc 10080 atcaccctaa tcaagttttt tggggtcgag gtgccgtaaa gcactaaatc ggaaccctaa 10140 agggagcccc cgatttagag cttgacgggg aaagccggcg aacgtggcga gaaaggaagg 10200 gaagaaagcg aaaggagcgg gcgctagggc gctggcaagt gtagcggtca cgctgcgcgt 10260 aaccaccaca cccgccgcgc ttaatgcgcc gctacagggc gcgtcccatt cgccattcag 10320 gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac gccagctggc 10380 gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt cccagtcacg 10440 acgttgtaaa acgacggcca gtgagcgcgc ggcgaattgg gtaccgggcc ccc 10493 <210> 23 <211> 10491 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 23 cctcgagggc tagccattct ccctatcagt gatagagatc tatttaagcc cgagtgagca 60 cgcagtccct atcagtgata gagaggtctc cattttgaag cgggaggttt gaacgcgcag 120 ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt gacgagcatc 180 tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg gagttgccgc 240 cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg gccgagaagc 300 tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag gctcttttct 360 ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg gaaaccaccg 420 gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa ctgattcaga 480 gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca aagaccagaa 540 atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat tacttgctcc 600 ccaaaaccca gcctgagctc caatgggcat ggaccaacat ggaacagtac ctcagcgcct 660 gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac gtgtcgcaga 720 cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg atcagatcaa 780 aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg attacctcgg 840 agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg gcctccaact 900 cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc ctgactaaaa 960 ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc aatcggattt 1020 ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc tttctgggat 1080 gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct gcaactaccg 1140 ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg tgcgtaaact 1200 ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc tggtgggagg 1260 aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctcgga ggaagcaagg 1320 tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc gtgatcgtca 1380 cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc gaacaccagc 1440 agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat catgactttg 1500 ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat cacgtggttg 1560 aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc gcccccagtg 1620 acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca tcgacgtcag 1680 acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct cgtcacgtgg 1740 gcatgaatct gatgctgttt ccctgcagac aatgcgagag aatgaatcag aattcaaata 1800 tctgcttcac tcacggacag aaagactgtt tagagtgctt tcccgtgtca gaatctcaac 1860 ccgtttctgt cgtcaaaaag gcgtatcaga aactgtgcta cattcatcat atcatgggaa 1920 aggtgccaga cgcttgcact gcctgcgatc tggtcaatgt ggatttggat gactgcatct 1980 ttgaacaata aatgatttaa atcaggtatg gctgccgatg gttatcttcc agattggctc 2040 gaggacaacc tctctgaggg cattcgcgag tggtgggact tgaaacctgg agccccgaaa 2100 cccaaagcca accagcaaaa gcaggacgac ggccggggtc tggtgcttcc tggctacaag 2160 tacctcggac ccttcaacgg actcgacaag ggggagcccg tcaacgcggc ggacgcagcg 2220 gccctcgagc acgacaaggc ctacgaccag cagctcaaag cgggtgacaa tccgtacctg 2280 cggtataacc acgccgacgc cgagtttcag gagcgtctgc aagaagatac gtcttttggg 2340 ggcaacctcg ggcgagcagt cttccaggcc aagaagcggg ttctcgaacc tctcggtctg 2400 gttgaggaag gcgctaagac ggctcctgga aagaagagac cggtagagca atcaccccag 2460 gaaccagact cctcttcggg catcggcaag aaaggccagc agcccgcgag aaagagactc 2520 aactttgggc agactggcga ctcagagtca gtgcccgacc ctcaaccact cggagaaccc 2580 cccgcagccc cctctggtgt gggatctaat acaatggctg caggcggtgg cgctccaatg 2640 gcagacaata acgaaggcgc cgacggagtg ggtaacgcct caggaaattg gcattgcgat 2700 tccacatggc tgggcgacag agtcatcacc accagcaccc gaacctgggc cctccccacc 2760 tacaacaacc acctctacaa gcaaatctcc agccaatcgg gaggcagcac caacgacaac 2820 acctacttcg gctacagcac cccctggggg tattttgact ttaacagatt ccactgccac 2880 ttctcaccac gtgactggca gcgactcatc aacaacaact ggggattccg gcccaagaag 2940 ctcaacttca agctcttcaa catccaggtc aaggaggtca cgacgaatga tggcaccacg 3000 accatcgcca ataaccttac cagcacggtt caggtcttta cggactcgga ataccagctc 3060 ccgtacgtcc tcggctctgc gcaccagggc tgcctgcctc cgttcccggc ggacgtcttc 3120 atgattcctc agtacgggta cctgactctg aacaatggca gtcaggccgt gggccgttcc 3180 tccttctact gcctggaata ctttccttct caaatgctga gaacgggcaa caactttcag 3240 ttcagctaca cgtttgagga cgtgcctttt cacagcagct acgcgcacag ccaaagcctg 3300 gaccggctga tgaaccccct catcgaccag tacctgtact acctgtctcg gactcagacc 3360 acgagtggta ccgcaggaaa tcggacgttg caattttctc aggccgggcc tagtagcatg 3420 gcgaatcagg ccaaaaactg gctacccggg ccctgctacc ggcagcaacg cgtctccaag 3480 acaaccaatc aaaataacaa cagcaacttt gcctggaccg gtgccaccaa gtatcatctg 3540 aatggcagag actctctggt aaatcccggt cccgctatgg caacccacaa ggacgacgaa 3600 gacaaatttt ttccgatgag cggagtctta atatttggga aacagggagc tggaaatagc 3660 aacgtggacc ttgacaacgt tatgataacc aacgaggaag aaattaaaac caccaaccca 3720 gtggccacag aagagtacgg cacggtggcc actaacctgc aatcggccaa caccgctcct 3780 gctacaggga ccgtcaacag tcaaggagcc ttacctggca tggtctggca ggaccgggac 3840 gtgtacctgc agggtcctat ctgggccaag attcctcaca cggacggaca ctttcatccc 3900 tcgccgctga tgggaggctt tggactgaaa cacccgcctc ctcagatcct gattaagaat 3960 acacctgttc ccgcgaatcc tccaactacc ttcagtccag ctaagtttgc gtcgttcatc 4020 acgcagtaca gcaccggaca ggtcagcgtg gaaattgaat gggagctgca gaaagaaaac 4080 agcaaacgct ggaacccaga gattcaatac acttccaact acaacaaatc tacaaatgtg 4140 gactttgctg ttgacacaaa tggcgtttat tctgagcctc gccccatcgg cacccgttac 4200 ctcacccgta atctgtaaac tagtttgctt gttaatcaat aaaccgttta attcgtttca 4260 gttgaacttt ggtctctgcg tatttctttc ttatctagtt tccatgctct agaggtcctg 4320 tattagaggt cacgtgagtg ttttgcgaca ttttgcgaca ccatgtggtc acgctgggta 4380 tttaagcccg agtgagcacg cagggtctcc attttgaagc gggaggtttg aacgcgcagc 4440 cgccaagccg aattctgcag atatcggggt tggggttgcg ccttttccaa ggcagccctg 4500 ggtttgcgca gggacgcggc tgctctgggc gtggttccgg gaaacgcagc ggcgccgacc 4560 ctgggtctcg cacattcttc acgtccgttc gcagcgtcac ccggatcttc gccgctaccc 4620 ttgtgggccc cccggcgacg cttcctgctc cgcccctaag tcgggaaggt tccttgcggt 4680 tcgcggcgtg ccggacgtga caaacggaag ccgcacgtct cactagtacc ctcgcagacg 4740 gacagcgcca gggagcaatg gcagcgcgcc gaccgcgatg ggctgtggcc aatagcggct 4800 gctcagcagg gcgcgccgag agcagcggcc gggaaggggc ggtgcgggag gcggggtgtg 4860 gggcggtagt gtgggccctg ttcctgcccg cgcggtgttc cgcattctgc aagcctccgg 4920 agcgcacgtc ggcagtcggc tccctcgttg accgaatcac cgacctctct ccccagaagc 4980 tcccgggagc ttgtatatcc attttcggat ctgatcagca cgtgttgaca attaatcatc 5040 ggcatagtat atcggcatag tataatacga caaggtgagg aacgccacca tggccaagcc 5100 tttgtctcaa gaagaatcca ccctcattga aagagcaacg gctacaatca acagcatccc 5160 catctctgaa gactacagcg tcgccagcgc agctctctct agcgacggcc gcatcttcac 5220 tggtgtcaat gtatatcatt ttactggggg accttgtgca gaactcgtgg tgctgggcac 5280 tgctgctgct gcggcagctg gcaacctgac ttgtatcgtc gcgatcggaa atgagaacag 5340 gggcatcttg agcccctgcg gacggtgccg acaggtgctt ctcgatctgc atcctgggat 5400 caaagccata gtgaaggaca gtgatggaca gccgacggca gttgggattc gtgaattgct 5460 gccctctggt tatgtgtggg agggctaagc acttcgtggc cgaggagcag gactgacacg 5520 tgctacgaga tttcgattcc accgccgcct tctatgaaag gttgggcttc ggaatcgttt 5580 tccgggacgc cggctggatg atcctccagc gcggggatct catgctggag ttcttcgccc 5640 accccaactt gtttattgca gcttataatg gttacaaata aagcaatagc atcacaaatt 5700 tcacaaataa agcatttttt tcactgcatt ctagttgtgg tttgtccaaa ctcatcaatg 5760 tatcttagcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat 5820 gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctctcct aggccagaaa 5880 tggcgccgga ggcgggaaca aggtggtgga tgagtgctac atccccaatt acttgctccc 5940 caaaacccag cctgagctcc agtgggcgtg gactaatatg gaatccctat cagtgataga 6000 gacagtattt aagcgcctgt ccctatcagt gatagagatt tgaatctcac ggagcgtaaa 6060 cggttggtgg cgcagcatct gtttaaacgc agacgcagga gcagaacaaa gagaatcaga 6120 atcccaattc tgatgcgccg gtgatcagat caaaaacttc agccaggtac atggagctgg 6180 tcgggtggct cgtggacaag gggattacct cggagaagca gtggattcag gaggaccagg 6240 cctcatacat ctccttcaat gcggcctcca actcgcggtc ccaaatcaag gctgccttgg 6300 acaatgcggg aaagattatg agcctgacta aaaccgcccc cgactacctg gtgggccagc 6360 agcccgtgga ggacatttcc agcaatcgga tttataaaat tttggaacta aacgggtacg 6420 atccccaata tgcggcttcc gtctttctgg gatgggccac gaaaaagttc ggcaagagga 6480 acaccatctg gctgtttggg cctgcaacta ccgggaagac caacatcgcg gaggccatag 6540 cccacactgt gcccttctac gggtgcgtaa actggaccaa tgagaacttt cccttcaacg 6600 actgtgtcga caagatggtg atctggtggg aggaggggaa gatgaccgcc aaggtcgtgg 6660 agtcggccaa agccattctc ggaggaagca aggtgcgcgt ggaccagaaa tgcaagtcct 6720 cggcccagat agacccgact cccgtgatcg tcacctccaa caccaacatg tgcgccgtga 6780 ttgacgggaa ctcaacgacc ttcgaacacc agcagccgtt gcaagaccgg atgttcaaat 6840 ttgaactcac ccgccgtctg gatcatgact ttgggaaggt caccaagcag gaagtcaaag 6900 actttttccg gtgggcaaag gatcacgtgg ttgaggtgga gcatgaattc tacgtcaaaa 6960 agggtggagc caagaaaaga cccgccccca gtgacgcaga tataagtgag cccaaacggg 7020 tgcgcgagtc agttgcgcag ccatcgacgt cagacgcgga agcttcgatc aactacgcag 7080 acaggtacca aaacaaatgt tctcgtcacg tgggcatgaa tctgatgctg tttccctgca 7140 gacaatgcga gagaatgaat cagaattcaa atatctgctt cactcacgga cagaaagact 7200 gtttagagtg ctttcccgtg tcagaatctc aacccgtttc tgtcgtcaaa aaggcgtatc 7260 agaaactgtg ctacattcat catatcatgg gaaaggtgcc agacgcttgc actgcctgcg 7320 atctggtcaa tgtggatttg gatgactgca tctttgaaca ataaactagt ttgcttgtta 7380 atcaataaac cgtttaattc gtttcagttg aactttggtc tctgcgtatt tctttcttat 7440 ctagtttcca tgctctagag tatacgatat ccatcacact ggcggccgct cgactagagc 7500 ggccgccacc gcggtggagc tccagctttt gttcgcgcgc ttggcgtaat catggtcata 7560 gctgtttcct gtgtgaaatt ccacagcctg gggtgcctaa ttgcgttgcg ctcactgccc 7620 gctttccagt cgggaaacct gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg 7680 agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg 7740 gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg cggtaatacg gttatccaca 7800 gaatcagggg ataacgcagg aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac 7860 cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc gcccccctga cgagcatcac 7920 aaaaatcgac gctcaagtca gaggtggcga aacccgacag gactataaag ataccaggcg 7980 tttccccctg gaagctccct cgtgcgctct cctgttccga ccctgccgct taccggatac 8040 ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc atagctcacg ctgtaggtat 8100 ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag 8160 cccgaccgct gcgccttatc cggtaactat cgtcttgagt ccaacccggt aagacacgac 8220 ttatcgccac tggcagcagc cactggtaac aggattagca gagcgaggta tgtaggcggt 8280 gctacagagt tcttgaagtg gtggcctaac tacggctaca ctagaagaac agtatttggt 8340 atctgcgctc tgctgaagcc agttaccttc ggaaaaagag ttggtagctc ttgatccggc 8400 aaacaaacca ccgctggtag cggtggtttt tttgtttgca agcagcagat tacgcgcaga 8460 aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc tcagtggaac 8520 gaaaactcac gttaagggat tttggtcatg agattatcaa aaaggatctt cacctagatc 8580 cttttaaatt aaaaatgaag ttttaaatca atctaaagta tatatgagta aacttggtct 8640 gacagaaata ataaaaaagc cggattaata atctggcttt ttatattctc tctctagtat 8700 ataaacgcag aaaggcccac ccgaaggtga gccagtgtga ctctagtatt attagaaaaa 8760 ctcatcgagc atcaaatgaa actgcaattt attcatatca ggattatcaa taccatattt 8820 ttgaaaaagc cgtttctgta atgaaggaga aaactcaccg aggcagttcc aaagaatggc 8880 aaggtcctgg taacggtctg cgattccgac ccgtccaaca tcaatacaac ctattaattt 8940 cccctcgtca aaaataaggt tatcaagtga gaaatcacca tgagtgacga ctgaatccgg 9000 tgagaatggc aagagcttgt gcatttcttt ccagacttgt tcaacaggcc agccattacg 9060 ctcgtcatca aaatcactcg catcaaccaa accgttattc atgcgtgatt gcgcctgagc 9120 aagacgaaat acacgatcgc tgttaaaagg acaattacaa acaggaatcg aatgtaaccg 9180 gcgcaggaac acggccagcg catcaacaat attttcacct gaatcaggat attcttctaa 9240 tacctggaag gctgttttcc caggaatcgc ggtggtgagt aaccacgcat catcaggagt 9300 acggataaaa tgcttgatgg tcgggagagg cataaactcc gtcagccagt tgagacggac 9360 catctcatct gtaacatcat tggcaacgct acctttgcca tgtttcagaa acaactctgg 9420 cgcatcgggc ttcccataca agcgatagat tgtcgcacct gattgcccga cattatcgcg 9480 agcccattta tacccatata aatcagcgtc catgttggag tttaagcgcg gacgggagca 9540 agacgtttcc cgttgaatat ggctcataac accccttgta ttactgttta tgtaagcaga 9600 cagttttatt gttcatgatg atatattttt atcttgtgca atgtaacatc agagattttg 9660 agacacaacg tggctttgtt gaataaatcg aacttttgct gagttgaagg atcagctcta 9720 gtaaaataat aaaaaagccg gattaataat ctggcttttt atattctctc tctagtatat 9780 aaacgcagaa aggcccaccc gaaggtgagc cagtgtgacg gcacatttcc ccgaaaagtg 9840 ccacctaaat tgtaagcgtt aatattttgt taaaattcgc gttaaatttt tgttaaatca 9900 gctcattttt taaccaatag gccgaaatcg gcaaaatccc ttataaatca aaagaataga 9960 ccgagatagg gttgagtgtt gttccagttt ggaacaagag tccactatta aagaacgtgg 10020 actccaacgt caaagggcga aaaaccgtct atcagggcga tggcccacta cgtgaaccat 10080 caccctaatc aagttttttg gggtcgaggt gccgtaaagc actaaatcgg aaccctaaag 10140 ggagcccccg atttagagct tgacggggaa agccggcgaa cgtggcgaga aaggaaggga 10200 agaaagcgaa aggagcgggc gctagggcgc tggcaagtgt agcggtcacg ctgcgcgtaa 10260 ccaccacacc cgccgcgctt aatgcgccgc tacagggcgc gtcccattcg ccattcaggc 10320 tgcgcaactg ttgggaaggg cgatcggtgc gggcctcttc gctattacgc cagctggcga 10380 aagggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc cagtcacgac 10440 gttgtaaaac gacggccagt gagcgcgcgg cgaattgggt accgggcccc c 10491 <210> 24 <211> 7567 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 24 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatct ccctatcagt 60 gatagagatc gcccgagtga gcacgcaggg tctccatttt gaagcgggag gtttgaacgc 120 gcagccgcca tgccggggtt ttacgagatt gtgattaagg tccccagcga ccttgacgag 180 catctgcccg gcatttctga cagctttgtg aactgggtgg ccgagaagga atgggagttg 240 ccgccagatt ctgacatgga tctgaatctg attgagcagg cacccctgac cgtggccgag 300 aagctgcagc gcgactttct gacggaatgg cgccgtgtga gtaaggcccc ggaggctctt 360 ttctttgtgc aatttgagaa gggagagagc tacttccaca tgcacgtgct cgtggaaacc 420 accggggtga aatccatggt tttgggacgt ttcctgagtc agattcgcga aaaactgatt 480 cagagaattt accgcgggat cgagccgact ttgccaaact ggttcgcggt cacaaagacc 540 agaaatggcg ccggaggcgg gaacaaggtg gtggatgagt gctacatccc caattacttg 600 ctccccaaaa cccagcctga gctccagtgg gcgtggacta atatggaaca gtatttaagg 660 taagttccct atcagtgata gagatctccc tatcagtgat agagatactg acatccactt 720 tgcctttctc tccacagcgc ctgtttgaat ctcacggagc gtaaacggtt ggtggcgcag 780 catctgacgc acgtgtcgca gacgcaggag cagaacaaag agaatcagaa tcccaattct 840 gatgcgccgg tgatcagatc aaaaacttca gccaggtaca tggagctggt cgggtggctc 900 gtggacaagg ggattacctc ggagaagcag tggatccagg aggaccaggc ctcatacatc 960 tccttcaatg cggcctccaa ctcgcggtcc caaatcaagg ctgccttgga caatgcggga 1020 aagattatga gcctgactaa aaccgccccc gactacctgg tgggccagca gcccgtggag 1080 gacatttcca gcaatcggat ttataaaatt ttggaactaa acgggtacga tccccaatat 1140 gcggcttccg tctttctggg atgggccacg aaaaagttcg gcaagaggaa caccatctgg 1200 ctgtttgggc ctgcaactac cgggaagacc aacatcgcgg aggccatagc ccacactgtg 1260 cccttctacg ggtgcgtaaa ctggaccaat gagaactttc ccttcaacga ctgtgtcgac 1320 aagatggtga tctggtggga ggaggggaag atgaccgcca aggtcgtgga gtcggccaaa 1380 gccattctcg gaggaagcaa ggtgcgcgtg gaccagaaat gcaagtcctc ggcccagata 1440 gacccgactc ccgtgatcgt cacctccaac accaacatgt gcgccgtgat tgacgggaac 1500 tcaacgacct tcgaacacca gcagccgttg caagaccgga tgttcaaatt tgaactcacc 1560 cgccgtctgg atcatgactt tgggaaggtc accaagcagg aagtcaaaga ctttttccgg 1620 tgggcaaagg atcacgtggt tgaggtggag catgaattct acgtcaaaaa gggtggagcc 1680 aagaaaagac ccgcccccag tgacgcagat ataagtgagc ccaaacgggt gcgcgagtca 1740 gttgcgcagc catcgacgtc agacgcggaa gcttcgatca actacgcaga caggtaccaa 1800 aacaaatgtt ctcgtcacgt gggcatgaat ctgatgctgt ttccctgcag acaatgcgag 1860 agaatgaatc agaattcaaa tatctgcttc actcacggac agaaagactg tttagagtgc 1920 tttcccgtgt cagaatctca acccgtttct gtcgtcaaaa aggcgtatca gaaactgtgc 1980 tacattcatc atatcatggg aaaggtgcca gacgcttgca ctgcctgcga tctggtcaat 2040 gtggatttgg atgactgcat ctttgaacaa taaatgattt aaatcaggta tggctgccga 2100 tggttatctt ccagattggc tcgaggacaa cctctctgag ggcattcgcg agtggtggga 2160 cttgaaacct ggagccccga aacccaaagc caaccagcaa aagcaggacg acggccgggg 2220 tctggtgctt cctggctaca agtacctcgg acccttcaac ggactcgaca agggggagcc 2280 cgtcaacgcg gcggacgcag cggccctcga gcacgacaag gcctacgacc agcagctcaa 2340 agcgggtgac aatccgtacc tgcggtataa ccacgccgac gccgagtttc aggagcgtct 2400 gcaagaagat acgtcttttg ggggcaacct cgggcgagca gtcttccagg ccaagaagcg 2460 ggttctcgaa cctctcggtc tggttgagga aggcgctaag acggctcctg gaaagaagag 2520 accggtagag caatcacccc aggaaccaga ctcctcttcg ggcatcggca agaaaggcca 2580 gcagcccgcg agaaagagac tcaactttgg gcagactggc gactcagagt cagtgcccga 2640 ccctcaacca ctcggagaac cccccgcagc cccctctggt gtgggatcta atacaatggc 2700 tgcaggcggt ggcgctccaa tggcagacaa taacgaaggc gccgacggag tgggtaacgc 2760 ctcaggaaat tggcattgcg attccacatg gctgggcgac agagtcatca ccaccagcac 2820 ccgaacctgg gccctcccca cctacaacaa ccacctctac aagcaaatct ccagccaatc 2880 gggaggcagc accaacgaca acacctactt cggctacagc accccctggg ggtattttga 2940 ctttaacaga ttccactgcc acttctcacc acgtgactgg cagcgactca tcaacaacaa 3000 ctggggattc cggcccaaga agctcaactt caagctcttc aacatccagg tcaaggaggt 3060 cacgacgaat gatggcacca cgaccatcgc caataacctt accagcacgg ttcaggtctt 3120 tacggactcg gaataccagc tcccgtacgt cctcggctct gcgcaccagg gctgcctgcc 3180 tccgttcccg gcggacgtct tcatgattcc tcagtacggg tacctgactc tgaacaatgg 3240 cagtcaggcc gtgggccgtt cctccttcta ctgcctggaa tactttcctt ctcaaatgct 3300 gagaacgggc aacaactttc agttcagcta cacgtttgag gacgtgcctt ttcacagcag 3360 ctacgcgcac agccaaagcc tggaccggct gatgaacccc ctcatcgacc agtacctgta 3420 ctacctgtct cggactcaga ccacgagtgg taccgcagga aatcggacgt tgcaattttc 3480 tcaggccggg cctagtagca tggcgaatca ggccaaaaac tggctacccg ggccctgcta 3540 ccggcagcaa cgcgtctcca agacaaccaa tcaaaataac aacagcaact ttgcctggac 3600 cggtgccacc aagtatcatc tgaatggcag agactctctg gtaaatcccg gtcccgctat 3660 ggcaacccac aaggacgacg aagacaaatt ttttccgatg agcggagtct taatatttgg 3720 gaaacaggga gctggaaata gcaacgtgga ccttgacaac gttatgataa ccaacgagga 3780 agaaattaaa accaccaacc cagtggccac agaagagtac ggcacggtgg ccactaacct 3840 gcaatcggcc aacaccgctc ctgctacagg gaccgtcaac agtcaaggag ccttacctgg 3900 catggtctgg caggaccggg acgtgtacct gcagggtcct atctgggcca agattcctca 3960 cacggacgga cactttcatc cctcgccgct gatgggaggc tttggactga aacacccgcc 4020 tcctcagatc ctgattaaga atacacctgt tcccgcgaat cctccaacta ccttcagtcc 4080 agctaagttt gcgtcgttca tcacgcagta cagcaccgga caggtcagcg tggaaattga 4140 atgggagctg cagaaagaaa acagcaaacg ctggaaccca gagattcaat acacttccaa 4200 ctacaacaaa tctacaaatg tggactttgc tgttgacaca aatggcgttt attctgagcc 4260 tcgccccatc ggcacccgtt acctcacccg taatctgtaa actagtttgc ttgttaatca 4320 ataaaccgtt taattcgttt cagttgaact ttggtctctg cgtatttctt tcttatctag 4380 tttccatgct ctagaggtcc tgtattagag gtcacgtgag tgttttgcga cattttgcga 4440 caccatgtgg tcacgctggg tatttaagcc cgagtgagca cgcagggtct ccattttgaa 4500 gcgggaggtt tgaacgcgca gccgccaagc cgaattctgc agatatccat cacactggcg 4560 gccgctcgac tagagcggcc gccaccgcgg tggagctcca gcttttgttc gcgcgcttgg 4620 cgtaatcatg gtcatagctg tttcctgtgt gaaattccac agcctggggt gcctaattgc 4680 gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat 4740 cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac 4800 tgactcgctg cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt 4860 aatacggtta tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaggcca 4920 gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc 4980 ccctgacgag catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact 5040 ataaagatac caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct 5100 gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcatag 5160 ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca 5220 cgaacccccc gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa 5280 cccggtaaga cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc 5340 gaggtatgta ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag 5400 aagaacagta tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg 5460 tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca 5520 gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc 5580 tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag 5640 gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata 5700 tgagtaaact tggtctgaca gaaataataa aaaagccgga ttaataatct ggctttttat 5760 attctctctc tagtatataa acgcagaaag gcccacccga aggtgagcca gtgtgactct 5820 agtattatta gaaaaactca tcgagcatca aatgaaactg caatttattc atatcaggat 5880 tatcaatacc atatttttga aaaagccgtt tctgtaatga aggagaaaac tcaccgaggc 5940 agttccaaag aatggcaagg tcctggtaac ggtctgcgat tccgacccgt ccaacatcaa 6000 tacaacctat taatttcccc tcgtcaaaaa taaggttatc aagtgagaaa tcaccatgag 6060 tgacgactga atccggtgag aatggcaaga gcttgtgcat ttctttccag acttgttcaa 6120 caggccagcc attacgctcg tcatcaaaat cactcgcatc aaccaaaccg ttattcatgc 6180 gtgattgcgc ctgagcaaga cgaaatacac gatcgctgtt aaaaggacaa ttacaaacag 6240 gaatcgaatg taaccggcgc aggaacacgg ccagcgcatc aacaatattt tcacctgaat 6300 caggatattc ttctaatacc tggaaggctg ttttcccagg aatcgcggtg gtgagtaacc 6360 acgcatcatc aggagtacgg ataaaatgct tgatggtcgg gagaggcata aactccgtca 6420 gccagttgag acggaccatc tcatctgtaa catcattggc aacgctacct ttgccatgtt 6480 tcagaaacaa ctctggcgca tcgggcttcc catacaagcg atagattgtc gcacctgatt 6540 gcccgacatt atcgcgagcc catttatacc catataaatc agcgtccatg ttggagttta 6600 agcgcggacg ggagcaagac gtttcccgtt gaatatggct cataacaccc cttgtattac 6660 tgtttatgta agcagacagt tttattgttc atgatgatat atttttatct tgtgcaatgt 6720 aacatcagag attttgagac acaacgtggc tttgttgaat aaatcgaact tttgctgagt 6780 tgaaggatca gctctagtaa aataataaaa aagccggatt aataatctgg ctttttatat 6840 tctctctcta gtatataaac gcagaaaggc ccacccgaag gtgagccagt gtgacggcac 6900 atttccccga aaagtgccac ctaaattgta agcgttaata ttttgttaaa attcgcgtta 6960 aatttttgtt aaatcagctc attttttaac caataggccg aaatcggcaa aatcccttat 7020 aaatcaaaag aatagaccga gatagggttg agtgttgttc cagtttggaa caagagtcca 7080 ctattaaaga acgtggactc caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc 7140 ccactacgtg aaccatcacc ctaatcaagt tttttggggt cgaggtgccg taaagcacta 7200 aatcggaacc ctaaagggag cccccgattt agagcttgac ggggaaagcc ggcgaacgtg 7260 gcgagaaagg aagggaagaa agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg 7320 gtcacgctgc gcgtaaccac cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc 7380 cattcgccat tcaggctgcg caactgttgg gaagggcgat cggtgcgggc ctcttcgcta 7440 ttacgccagc tggcgaaagg gggatgtgct gcaaggcgat taagttgggt aacgccaggg 7500 ttttcccagt cacgacgttg taaaacgacg gccagtgagc gcgcggcgaa ttgggtaccg 7560 ggccccc 7567 <210> 25 <211> 7567 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 25 cctcgagggc tagccattct atttaatctc cctatcagtg atagagatct ccctatcagt 60 gatagagatc gcccgagtga gcacgcaggg tctccatttt gaagcgggag gtttgaacgc 120 gcagccgcca tgccggggtt ttacgagatt gtgattaagg tccccagcga ccttgacgag 180 catctgcccg gcatttctga cagctttgtg aactgggtgg ccgagaagga atgggagttg 240 ccgccagatt ctgacatgga tctgaatctg attgagcagg cacccctgac cgtggccgag 300 aagctgcagc gcgactttct gacggaatgg cgccgtgtga gtaaggcccc ggaggctctt 360 ttctttgtgc aatttgagaa gggagagagc tacttccaca tgcacgtgct cgtggaaacc 420 accggggtga aatccatggt tttgggacgt ttcctgagtc agattcgcga aaaactgatt 480 cagagaattt accgcgggat cgagccgact ttgccaaact ggttcgcggt cacaaagacc 540 agaaatggcg ccggaggcgg gaacaaggtg gtggatgagt gctacatccc caattacttg 600 ctccccaaaa cccagcctga gctccagtgg gcgtggacta atatggaaca gtatttaagc 660 gcctgtttga atctcacgga aaggtaagtt ccctatcagt gatagagatc tccctatcag 720 tgatagagat actgacatcc actttgcctt tctctccaca ggaaacggtt ggtggcgcag 780 catctgacgc acgtgtcgca gacgcaggag cagaacaaag agaatcagaa tcccaattct 840 gatgcgccgg tgatcagatc aaaaacttca gccaggtaca tggagctggt cgggtggctc 900 gtggacaagg ggattacctc ggagaagcag tggatccagg aggaccaggc ctcatacatc 960 tccttcaatg cggcctccaa ctcgcggtcc caaatcaagg ctgccttgga caatgcggga 1020 aagattatga gcctgactaa aaccgccccc gactacctgg tgggccagca gcccgtggag 1080 gacatttcca gcaatcggat ttataaaatt ttggaactaa acgggtacga tccccaatat 1140 gcggcttccg tctttctggg atgggccacg aaaaagttcg gcaagaggaa caccatctgg 1200 ctgtttgggc ctgcaactac cgggaagacc aacatcgcgg aggccatagc ccacactgtg 1260 cccttctacg ggtgcgtaaa ctggaccaat gagaactttc ccttcaacga ctgtgtcgac 1320 aagatggtga tctggtggga ggaggggaag atgaccgcca aggtcgtgga gtcggccaaa 1380 gccattctcg gaggaagcaa ggtgcgcgtg gaccagaaat gcaagtcctc ggcccagata 1440 gacccgactc ccgtgatcgt cacctccaac accaacatgt gcgccgtgat tgacgggaac 1500 tcaacgacct tcgaacacca gcagccgttg caagaccgga tgttcaaatt tgaactcacc 1560 cgccgtctgg atcatgactt tgggaaggtc accaagcagg aagtcaaaga ctttttccgg 1620 tgggcaaagg atcacgtggt tgaggtggag catgaattct acgtcaaaaa gggtggagcc 1680 aagaaaagac ccgcccccag tgacgcagat ataagtgagc ccaaacgggt gcgcgagtca 1740 gttgcgcagc catcgacgtc agacgcggaa gcttcgatca actacgcaga caggtaccaa 1800 aacaaatgtt ctcgtcacgt gggcatgaat ctgatgctgt ttccctgcag acaatgcgag 1860 agaatgaatc agaattcaaa tatctgcttc actcacggac agaaagactg tttagagtgc 1920 tttcccgtgt cagaatctca acccgtttct gtcgtcaaaa aggcgtatca gaaactgtgc 1980 tacattcatc atatcatggg aaaggtgcca gacgcttgca ctgcctgcga tctggtcaat 2040 gtggatttgg atgactgcat ctttgaacaa taaatgattt aaatcaggta tggctgccga 2100 tggttatctt ccagattggc tcgaggacaa cctctctgag ggcattcgcg agtggtggga 2160 cttgaaacct ggagccccga aacccaaagc caaccagcaa aagcaggacg acggccgggg 2220 tctggtgctt cctggctaca agtacctcgg acccttcaac ggactcgaca agggggagcc 2280 cgtcaacgcg gcggacgcag cggccctcga gcacgacaag gcctacgacc agcagctcaa 2340 agcgggtgac aatccgtacc tgcggtataa ccacgccgac gccgagtttc aggagcgtct 2400 gcaagaagat acgtcttttg ggggcaacct cgggcgagca gtcttccagg ccaagaagcg 2460 ggttctcgaa cctctcggtc tggttgagga aggcgctaag acggctcctg gaaagaagag 2520 accggtagag caatcacccc aggaaccaga ctcctcttcg ggcatcggca agaaaggcca 2580 gcagcccgcg agaaagagac tcaactttgg gcagactggc gactcagagt cagtgcccga 2640 ccctcaacca ctcggagaac cccccgcagc cccctctggt gtgggatcta atacaatggc 2700 tgcaggcggt ggcgctccaa tggcagacaa taacgaaggc gccgacggag tgggtaacgc 2760 ctcaggaaat tggcattgcg attccacatg gctgggcgac agagtcatca ccaccagcac 2820 ccgaacctgg gccctcccca cctacaacaa ccacctctac aagcaaatct ccagccaatc 2880 gggaggcagc accaacgaca acacctactt cggctacagc accccctggg ggtattttga 2940 ctttaacaga ttccactgcc acttctcacc acgtgactgg cagcgactca tcaacaacaa 3000 ctggggattc cggcccaaga agctcaactt caagctcttc aacatccagg tcaaggaggt 3060 cacgacgaat gatggcacca cgaccatcgc caataacctt accagcacgg ttcaggtctt 3120 tacggactcg gaataccagc tcccgtacgt cctcggctct gcgcaccagg gctgcctgcc 3180 tccgttcccg gcggacgtct tcatgattcc tcagtacggg tacctgactc tgaacaatgg 3240 cagtcaggcc gtgggccgtt cctccttcta ctgcctggaa tactttcctt ctcaaatgct 3300 gagaacgggc aacaactttc agttcagcta cacgtttgag gacgtgcctt ttcacagcag 3360 ctacgcgcac agccaaagcc tggaccggct gatgaacccc ctcatcgacc agtacctgta 3420 ctacctgtct cggactcaga ccacgagtgg taccgcagga aatcggacgt tgcaattttc 3480 tcaggccggg cctagtagca tggcgaatca ggccaaaaac tggctacccg ggccctgcta 3540 ccggcagcaa cgcgtctcca agacaaccaa tcaaaataac aacagcaact ttgcctggac 3600 cggtgccacc aagtatcatc tgaatggcag agactctctg gtaaatcccg gtcccgctat 3660 ggcaacccac aaggacgacg aagacaaatt ttttccgatg agcggagtct taatatttgg 3720 gaaacaggga gctggaaata gcaacgtgga ccttgacaac gttatgataa ccaacgagga 3780 agaaattaaa accaccaacc cagtggccac agaagagtac ggcacggtgg ccactaacct 3840 gcaatcggcc aacaccgctc ctgctacagg gaccgtcaac agtcaaggag ccttacctgg 3900 catggtctgg caggaccggg acgtgtacct gcagggtcct atctgggcca agattcctca 3960 cacggacgga cactttcatc cctcgccgct gatgggaggc tttggactga aacacccgcc 4020 tcctcagatc ctgattaaga atacacctgt tcccgcgaat cctccaacta ccttcagtcc 4080 agctaagttt gcgtcgttca tcacgcagta cagcaccgga caggtcagcg tggaaattga 4140 atgggagctg cagaaagaaa acagcaaacg ctggaaccca gagattcaat acacttccaa 4200 ctacaacaaa tctacaaatg tggactttgc tgttgacaca aatggcgttt attctgagcc 4260 tcgccccatc ggcacccgtt acctcacccg taatctgtaa actagtttgc ttgttaatca 4320 ataaaccgtt taattcgttt cagttgaact ttggtctctg cgtatttctt tcttatctag 4380 tttccatgct ctagaggtcc tgtattagag gtcacgtgag tgttttgcga cattttgcga 4440 caccatgtgg tcacgctggg tatttaagcc cgagtgagca cgcagggtct ccattttgaa 4500 gcgggaggtt tgaacgcgca gccgccaagc cgaattctgc agatatccat cacactggcg 4560 gccgctcgac tagagcggcc gccaccgcgg tggagctcca gcttttgttc gcgcgcttgg 4620 cgtaatcatg gtcatagctg tttcctgtgt gaaattccac agcctggggt gcctaattgc 4680 gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat 4740 cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac 4800 tgactcgctg cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt 4860 aatacggtta tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaggcca 4920 gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc 4980 ccctgacgag catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact 5040 ataaagatac caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct 5100 gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcatag 5160 ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca 5220 cgaacccccc gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa 5280 cccggtaaga cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc 5340 gaggtatgta ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag 5400 aagaacagta tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg 5460 tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca 5520 gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc 5580 tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag 5640 gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata 5700 tgagtaaact tggtctgaca gaaataataa aaaagccgga ttaataatct ggctttttat 5760 attctctctc tagtatataa acgcagaaag gcccacccga aggtgagcca gtgtgactct 5820 agtattatta gaaaaactca tcgagcatca aatgaaactg caatttattc atatcaggat 5880 tatcaatacc atatttttga aaaagccgtt tctgtaatga aggagaaaac tcaccgaggc 5940 agttccaaag aatggcaagg tcctggtaac ggtctgcgat tccgacccgt ccaacatcaa 6000 tacaacctat taatttcccc tcgtcaaaaa taaggttatc aagtgagaaa tcaccatgag 6060 tgacgactga atccggtgag aatggcaaga gcttgtgcat ttctttccag acttgttcaa 6120 caggccagcc attacgctcg tcatcaaaat cactcgcatc aaccaaaccg ttattcatgc 6180 gtgattgcgc ctgagcaaga cgaaatacac gatcgctgtt aaaaggacaa ttacaaacag 6240 gaatcgaatg taaccggcgc aggaacacgg ccagcgcatc aacaatattt tcacctgaat 6300 caggatattc ttctaatacc tggaaggctg ttttcccagg aatcgcggtg gtgagtaacc 6360 acgcatcatc aggagtacgg ataaaatgct tgatggtcgg gagaggcata aactccgtca 6420 gccagttgag acggaccatc tcatctgtaa catcattggc aacgctacct ttgccatgtt 6480 tcagaaacaa ctctggcgca tcgggcttcc catacaagcg atagattgtc gcacctgatt 6540 gcccgacatt atcgcgagcc catttatacc catataaatc agcgtccatg ttggagttta 6600 agcgcggacg ggagcaagac gtttcccgtt gaatatggct cataacaccc cttgtattac 6660 tgtttatgta agcagacagt tttattgttc atgatgatat atttttatct tgtgcaatgt 6720 aacatcagag attttgagac acaacgtggc tttgttgaat aaatcgaact tttgctgagt 6780 tgaaggatca gctctagtaa aataataaaa aagccggatt aataatctgg ctttttatat 6840 tctctctcta gtatataaac gcagaaaggc ccacccgaag gtgagccagt gtgacggcac 6900 atttccccga aaagtgccac ctaaattgta agcgttaata ttttgttaaa attcgcgtta 6960 aatttttgtt aaatcagctc attttttaac caataggccg aaatcggcaa aatcccttat 7020 aaatcaaaag aatagaccga gatagggttg agtgttgttc cagtttggaa caagagtcca 7080 ctattaaaga acgtggactc caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc 7140 ccactacgtg aaccatcacc ctaatcaagt tttttggggt cgaggtgccg taaagcacta 7200 aatcggaacc ctaaagggag cccccgattt agagcttgac ggggaaagcc ggcgaacgtg 7260 gcgagaaagg aagggaagaa agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg 7320 gtcacgctgc gcgtaaccac cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc 7380 cattcgccat tcaggctgcg caactgttgg gaagggcgat cggtgcgggc ctcttcgcta 7440 ttacgccagc tggcgaaagg gggatgtgct gcaaggcgat taagttgggt aacgccaggg 7500 ttttcccagt cacgacgttg taaaacgacg gccagtgagc gcgcggcgaa ttgggtaccg 7560 ggccccc 7567 <210> 26 <211> 11801 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 26 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcgtttaaac ttaagcttgg taccgagctc ggatccacta 1560 gtccagtgtg gtggaattcc tgcttcgcga tgtacgggcc agatatacgc gttgacattg 1620 attattgact agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat 1680 ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc 1740 ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca 1800 ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta 1860 tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 1920 tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 1980 cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 2040 ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggaacca 2100 aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 2160 taggcgtgta cggtgggagg tctatataag cagagctctc cctatcagtg atagagatct 2220 ccctatcagt gatagagatc gtcgacgagc tcgtttagtg aaccgtcaga tcgcctggag 2280 acgccatcca cgctgttttg acctccatag aagacaccgg gaccgatcca gcctccggac 2340 tctagcgttt aaacttaagc ttgccaccat ggccagtcgg gaagaggagc agcgcgaaac 2400 cacccccgag cgcggacgcg gtgcggcgcg acgtccccca accatggagg acgtgtcgtc 2460 cccgtccccg tcgccgccgc ctccccgggc gcccccaaaa aagcggatga ggcggcgtat 2520 cgagtccgag gacgaggaag actcatcaca agacgcgctg gtgccgcgca cacccagccc 2580 gcggccatcg acctcggcgg cggatttggc cattgcgccc aagaagaaaa agaagcgccc 2640 ttctcccaag cccgagcgcc cgccatcacc agaggtaatc gtggacagcg aggaagaaag 2700 agaagatgtg gcgctacaaa tggtgggttt cagcaaccca ccggtgctaa tcaagcatgg 2760 caaaggaggt aagcgcacag tgcggcggct gaatgaagac gacccagtgg cgcgtggtat 2820 gcggacgcaa gaggaagagg aagagcccag cgaagcggaa agtgaaatta cggtgatgaa 2880 cccgctgagt gtgccgatcg tgtctgcgtg ggagaagggc atggaggctg cgcgcgcgct 2940 gatggacaag taccacgtgg ataacgatct aaaggcgaac ttcaaactac tgcctgacca 3000 agtggaagct ctggcggccg tatgcaagac ctggctgaac gaggagcacc gcgggttgca 3060 gctgaccttc accagcaaca agacctttgt gacgatgatg gggcgattcc tgcaggcgta 3120 cctgcagtcg tttgcagagg tgacctacaa gcatcacgag cccacgggct gcgcgttgtg 3180 gctgcaccgc tgcgctgaga tcgaaggcga gcttaagtgt ctacacggaa gcattatgat 3240 aaataaggag cacgtgattg aaatggatgt gacgagcgaa aacgggcagc gcgcgctgaa 3300 ggagcagtct agcaaggcca agatcgtgaa gaaccggtgg ggccgaaatg tggtgcagat 3360 ctccaacacc gacgcaaggt gctgcgtgca cgacgcggcc tgtccggcca atcagttttc 3420 cggcaagtct tgcggcatgt tcttctctga aggcgcaaag gctcaggtgg cttttaagca 3480 gatcaaggct tttatgcagg cgctgtatcc taacgcccag accgggcacg gtcacctttt 3540 gatgccacta cggtgcgagt gcaactcaaa gcctgggcac gcgccctttt tgggaaggca 3600 gctaccaaag ttgactccgt tcgccctgag caacgcggag gacctggacg cggatctgat 3660 ctccgacaag agcgtgctgg ccagcgtgca ccacccggcg ctgatagtgt tccagtgctg 3720 caaccctgtg tatcgcaact cgcgcgcgca gggcggaggc cccaactgcg acttcaagat 3780 atcggcgccc gacctgctaa acgcgttggt gatggtgcgc agcctgtgga gtgaaaactt 3840 caccgagctg ccgcggatgg ttgtgcctga gtttaagtgg agcactaaac accagtatcg 3900 caacgtgtcc ctgccagtgg cgcatagcga tgcgcggcag aacccctttg atttttaacc 3960 cgggagttct agggatctgc ccctctccct cccccccccc taacgttact ggccgaagcc 4020 gcttggaata aggccggtgt gcgtttgtct atatgttatt ttccaccata ttgccgtctt 4080 ttggcaatgt gagggcccgg aaacctggcc ctgtcttctt gacgagcatt cctaggggtc 4140 tttcccctct cgccaaagga atgcaaggtc tgttgaatgt cgtgaaggaa gcagttcctc 4200 tggaagcttc ttgaagacaa acaacgtctg tagcgaccct ttgcaggcag cggaaccccc 4260 cacctggcga caggtgcctc tgcggccaaa agccacgtgt ataagataca cctgcaaagg 4320 cggcacaacc ccagtgccac gttgtgagtt ggatagttgt ggaaagagtc aaatggctct 4380 cctcaagcgt attcaacaag gggctgaagg atgcccagaa ggtaccccat tgtatgggat 4440 ctgatctggg gcctcggtgc acatgcttta catgtgttta gtcgaggtta aaaaaacgtc 4500 taggcccccc gaaccacggg gacgtggttt tcctttgaaa aacacgatga taaggatcca 4560 ccggaggcca ccatgactac gtccggcgtt ccatttggca tgacactacg accaacacga 4620 tctcggttgt ctcggcgcac tccgtacagt agggatcgtc tacctccttt tgagacagaa 4680 acccgcgcta ccatactgga ggatcatccg ctgctgcccg aatgtaacac tttgacaatg 4740 cacaacgtga gttacgtgcg aggtcttccc tgcagtgtgg gatttacgct gattcaggaa 4800 tgggttgttc cctgggatat ggttctaacg cgggaggagc ttgtaatcct gaggaagtgt 4860 atgcacgtgt gcctgtgttg tgccaacatt gatatcatga cgagcatgat gatccatggt 4920 tacgagtcct gggctctcca ctgtcattgt tccagtcccg gttccctgca gtgtatagcc 4980 ggcgggcagg ttttggccag ctggtttagg atggtggtgg atggcgccat gtttaatcag 5040 aggtttatat ggtaccggga ggtggtgaat tacaacatgc caaaagaggt aatgtttatg 5100 tccagcgtgt ttatgagggg tcgccactta atctacctgc gcttgtggta tgatggccac 5160 gtgggttctg tggtccccgc catgagcttt ggatacagcg ccttgcactg tgggattttg 5220 aacaatattg tggtgctgtg ctgcagttac tgtgctgatt taagtgagat cagggtgcgc 5280 tgctgtgccc ggaggacaag gcgccttatg ctgcgggcgg tgcgaatcat cgctgaggag 5340 accactgcca tgttgtattc ctgcaggacg gagcggcggc ggcagcagtt tattcgcgcg 5400 ctgctgcagc accaccgccc tatcctgatg cacgattatg actctacccc catgtaggcg 5460 gccgtcgagt ctagagggcc cgtttaaacc cgctgatcag cctcgactgt gccttctagt 5520 tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 5580 cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 5640 tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 5700 aggcatgctg gggatgcggt gggctctatg gcttctgagg cggaaagaac cagctggggc 5760 tctagggggt atccccggcg cgccggggtt gagctattcc agaagtagtg aagaggcttt 5820 tttggaggcc taggcttttg caaaaagctc cggatcgatt ggggttgcgc cttttccaag 5880 gcttttcccc gtatcccccc aggtgtctgc aggctcaaag agcagcgaga agcgttcaga 5940 ggaaagcgat cccgtgccac cttccccgtg cccgggctgt ccccgcacgc tgccggctcg 6000 gggatgcggg gggagcgccg gaccggagcg gagccccggg cggctcgctg ctgcccccta 6060 gcgggggagg gacgtaatta catccctggg ggctttgggg gggggctgtc cctctagggg 6120 atcctctagg gcctctgagc tattccagaa gtagtgaaga ggcttttttg gaggcctagg 6180 cttttgcaaa aagctccgga tcgatcgagc ggatccagca cagtggcggc cgcaatattt 6240 gcatgtcgct atgtgttctg ggaaatcacc ataaacgtga aatccctatc agtgatagag 6300 acttataagt tccctatcag tgatagagaa ccggtgggca ctcttccgtg gtctggtgga 6360 taaattcgca agggtatcat ggcggacgac cggggttcga gccccgtatc cggccgtccg 6420 ccgtgatcca tgcggttacc gcccgcgtgt cgaacccagg tgtgcgacgt cagacaacgg 6480 gggagtgctc ctttttgaat tccactttgg ccgcggctcg agtgagctat tccagaagta 6540 gtgaagaggc ttttttggag gcctaggctt ttgcaaaaag ctccggatcg atgcccgggg 6600 gatccactag ttctagaggg acagcccccc cccaaagccc ccagggatgt aattacgtcc 6660 ctcccccgct agggggcagc agcgagccgc ccggggctcc gctccggtcc ggcgctcccc 6720 ccgcatcccc gagccggcag cgtgcgggga cagcccgggc acggggaagg tggcacggga 6780 tcgctttcct ctgaacgctt ctcgctgctc tttgagcctg cagacacctg gggggatacg 6840 gggaaaaggc ctccaaggcc agcttcccac aataagttgg gtgaattttg gctgagctat 6900 tccagaagta gtgaagaggc ttttttggag gcctaggctt ttgcaaaaag ctccggatcg 6960 atcatatatg gcagatatac gcgttgacat tgattattga ctagttatta atagtaatca 7020 attacggggt cattagttca tagcccatat atggagttcc gcgttacata acttacggta 7080 aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat aatgacgtat 7140 gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga gtatttacgg 7200 taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc ccctattgac 7260 gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt atgggacttt 7320 cctacttggc agtacatcta cgtattagtc atcgctatta ccatggtgat gcggttttgg 7380 cagtacatca atgggcgtgg atagcggttt gactcacggg gatttccaag tctccacccc 7440 attgacgtca atgggagttt gttttggcac caaaatcaac gggactttcc aaaatgtcgt 7500 aacaactccg ccccattgac gcaaatgggc ggtaggcgtg tacggtggga ggtctatata 7560 agcagagctc tctggctaac tatcgtcgac gagctcgttt agtgaaccgt cagatcgcct 7620 ggagacgcca tccacgctgt tttgacctcc atagaagaca ccgggaccga tccagcctcc 7680 ggactctagc gtttaaactt aagcttgcca ccatgaccga gtacaagccc acggtgcgcc 7740 tcgccacccg cgacgacgtc cccagggccg tacgcaccct cgccgccgcg ttcgccgact 7800 accccgccac gcgccacacc gtcgatccgg accgccacat cgagcgggtc accgagctgc 7860 aagaactctt cctcacgcgc gtcgggctcg acatcggcaa ggtgtgggtc gcggacgacg 7920 gcgccgcggt ggcggtctgg accacgccgg agagcgtcga agcgggggcg gtgttcgccg 7980 agatcggccc gcgcatggcc gagttgagcg gttcccggct ggccgcgcag caacagatgg 8040 aaggcctcct ggcgccgcac cggcccaagg agcccgcgtg gttcctggcc accgtcggcg 8100 tctcgcccga ccaccagggc aagggtctgg gcagcgccgt cgtgctcccc ggagtggagg 8160 cggccgagcg cgccggggtg cccgccttcc tggagacctc cgcgccccgc aacctcccct 8220 tctacgagcg gctcggcttc accgtcaccg ccgacgtcga ggtgcccgaa ggaccgcgca 8280 cctggtgcat gacccgcaag cccggtgcct gaagcgcggg gatctcatgc tggagttctt 8340 cgcccacccc aacttgttta ttgcagctta taatggttac aaataaagca atagcatcac 8400 aaatttcaca aataaagcat ttttttcact gcattctagt tgtggtttgt ccaaactcat 8460 caatgtatct tatcatgtct gtagctgatg tatacctagg atccggccgg cctgcaggtg 8520 tcctcacagg aacgaagtcc ctaaagaaac agtggcagcc aggtttagcc ccggaattga 8580 ctggattcct tttttagggc ccattggtat ggctttttcc ccgtatcccc ccaggtgtct 8640 gcaggctcaa agagcagcga gaagcgttca gaggaaagcg atcccgtgcc accttccccg 8700 tgcccgggct gtccccgcac gctgccggct cggggatgcg gggggagcgc cggaccggag 8760 cggagccccg ggcggctcgc tgctgccccc tagcggggga gggacgtaat tacatccctg 8820 ggggctttgg gggggggctg tccctctaga gcggccgcca ccgcggtgga gctccagctt 8880 ttgttccctt tagtgagggt taattagatc ttaatacgac tcactatagg gcgaattggg 8940 taccgggccc cccctcgagg tcgacggtat cgataagctt gatatctata acaagaaaat 9000 atatatataa taagttatca cgtaagtaga acatgaaata acaatataat tatcgtatga 9060 gttaaatctt aaaagtcacg taaaagataa tcatgcgtca ttttgactca cgcggtcgtt 9120 atagttcaaa atcagtgaca cttaccgcat tgacaagcac gcctcacggg agctccaagc 9180 ggcgactgag atgtcctaaa tgcacagcga cggattcgcg ctatttagaa agagagagca 9240 atatttcaag aatgcatgcg tcaattttac gcagactatc tttctagggt taatctagct 9300 gcatcaggat catatcgtcg ggtctttttt ccggctcagt catcgcccaa gctggcgcta 9360 tctgggcatc ggggaggaag aagcccgtgc cttttcccgc gaggttgaag cggcatggaa 9420 agagtttgcc gaggatgact gctgctgcat tgacgttgag cgaaaacgca cgtttaccat 9480 gatgattcgg gaaggtgtgg ccatgcacgc ctttaacggt gaactgttcg ttcaggccac 9540 ctgggatacc agttcgtcgc ggcttttccg gacacagttc cggatggtca gcccgaagcg 9600 catcagcaac ccgaacaata ccggcgacag ccggaactgc cgtgccggtg tgcagattaa 9660 tgacagcggt gcggcgctgg gatattacgt cagcgaggac gggtatcctg gctggatgcc 9720 gcagaaatgg acatggatac cccgtgagtt acccggcggg cgcgcttggc gtaatcatgg 9780 tcatagctgt ttcctgtgtg aaattgttat ccgctcacaa ttccacacaa catacgagcc 9840 ggaagcataa agtgtaaagc ctggggtgcc taatgagtga gctaactcac attaattgcg 9900 ttgcgctcac tgcccgcttt ccagtcggga aacctgtcgt gccagctgca ttaatgaatc 9960 ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc ctcgctcact 10020 gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc aaaggcggta 10080 atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc aaaaggccag 10140 caaaaggcca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag gctccgcccc 10200 cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc gacaggacta 10260 taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt tccgaccctg 10320 ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct ttctcatagc 10380 tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg ctgtgtgcac 10440 gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct tgagtccaac 10500 ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat tagcagagcg 10560 aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg ctacactaga 10620 aggacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa aagagttggt 10680 agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt ttgcaagcag 10740 cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc tacggggtct 10800 gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt atcaaaaagg 10860 atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta aagtatatat 10920 gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat ctcagcgatc 10980 tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac tacgatacgg 11040 gagggcttac catctggccc cagtgctgca atgataccgc gagacccacg ctcaccggct 11100 ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag tggtcctgca 11160 actttatccg cctccatcca gtctattaat tgttgccggg aagctagagt aagtagttcg 11220 ccagttaata gtttgcgcaa cgttgttgcc attgctacag gcatcgtggt gtcacgctcg 11280 tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt tacatgatcc 11340 cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt cagaagtaag 11400 ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct tactgtcatg 11460 ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt ctgagaatag 11520 tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatac cgcgccacat 11580 agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa actctcaagg 11640 atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa ctgatcttca 11700 gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca aaatgccgca 11760 aaaaagggaa taagggcgac acggaaatgt tgaatactca t 11801 <210> 27 <211> 7798 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 27 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcaaacgcca gcaacgcggc ctttttacgg ttcctggcct 1560 tttgctggcc ttttgctcac atgtcctgca ggcagctgcg cgctcgctcg ctcactgagg 1620 ccgcccgggc aaagcccggg cgtcgggcga cctttggtcg cccggcctca gtgagcgagc 1680 gagcgcgcag agagggagtg gccaactcca tcactagggg ttcctgcggc cgcacgcgtg 1740 gagctagtta ttaatagtaa tcaattacgg ggtcattagt tcatagccca tatatggagt 1800 tccgcgttac ataacttacg gtaaatggcc cgcctggctg accgcccaac gacccccgcc 1860 cattgacgtc aataatgacg tatgttccca tagtaacgtc aatagggact ttccattgac 1920 gtcaatgggt ggagtattta cggtaaactg cccacttggc agtacatcaa gtgtatcata 1980 tgccaagtac gccccctatt gacgtcaatg acggtaaatg gcccgcctgg cattatgccc 2040 agtacatgac cttatgggac tttcctactt ggcagtacat ctacgtatta gtcatcgcta 2100 ttaccatggt gatgcggttt tggcagtaca tcaatgggcg tggatagcgg tttgactcac 2160 ggggatttcc aagtctccac cccattgacg tcaatgggag tttgttttgc accaaaatca 2220 acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg gcggtaggcg 2280 tgtacggtgg gaggtctata taagcagagc tcgtttagtg aaccgtcaga tcgcctggag 2340 acgccatcca cgctgttttg acctccatag aagacaccgg gaccgatcca gcctccgcgg 2400 attcgaatcc cggccgggaa cggtgcattg gaacgcggat tccccgtgcc aagagtgacg 2460 taagtaccgc ctatagagtc tataggccca caaaaaatgc tttcttcttt taatatactt 2520 ttttgtttat cttatttcta atactttccc taatctcttt ctttcagggc aataatgata 2580 caatgtatca tgcctctttg caccattcta aagaataaca gtgataattt ctgggttaag 2640 gcaatagcaa tatttctgca tataaatatt tctgcatata aattgtaact gatgtaagag 2700 gtttcatatt gctaatagca gctacaatcc agctaccatt ctgcttttat tttatggttg 2760 ggataaggct ggattattct gagtccaagc taggcccttt tgctaatcat gttcatacct 2820 cttatcttcc tcccacagct cctgggcaac gtgctggtct gtgtgctggc ccatcacttt 2880 ggcaaagaat tgggattcga acatcgattg aattctgaat ggtgagcaag ggcgaggagc 2940 tgttcaccgg ggtggtgccc atcctggtcg agctggacgg cgacgtaaac ggccacaagt 3000 tcagcgtgtc cggcgagggc gagggcgatg ccacctacgg caagctgacc ctgaagttca 3060 tctgcaccac cggcaagctg cccgtgccct ggcccaccct cgtgaccacc ctgacctacg 3120 gcgtgcagtg cttcagccgc taccccgacc acatgaagca gcacgacttc ttcaagtccg 3180 ccatgcccga aggctacgtc caggagcgca ccatcttctt caaggacgac ggcaactaca 3240 agacccgcgc cgaggtgaag ttcgagggcg acaccctggt gaaccgcatc gagctgaagg 3300 gcatcgactt caaggaggac ggcaacatcc tggggcacaa gctggagtac aactacaaca 3360 gccacaacgt ctatatcatg gccgacaagc agaagaacgg catcaaggtg aacttcaaga 3420 tccgccacaa catcgaggac ggcagcgtgc agctcgccga ccactaccag cagaacaccc 3480 ccatcggcga cggccccgtg ctgctgcccg acaaccacta cctgagcacc cagtccgccc 3540 tgagcaaaga ccccaacgag aagcgcgatc acatggtcct gctggagttc gtgaccgccg 3600 ccgggatcac tctcggcatg gacgagctgt acaagtactc agatctcgag ctcaagtagg 3660 gatcctctag agtcgacctg cagaagcttg cctcgagcag cgctgctcga gagatctacg 3720 ggtggcatcc ctgtgacccc tccccagtgc ctctcctggc cctggaagtt gccactccag 3780 tgcccaccag ccttgtccta ataaaattaa gttgcatcat tttgtctgac taggtgtcct 3840 tctataatat tatggggtgg aggggggtgg tatggagcaa ggggcaagtt gggaagacaa 3900 cctgtagggc ctgcggggtc tattgggaac caagctggag tgcagtggca caatcttggc 3960 tcactgcaat ctccgcctcc tgggttcaag cgattctcct gcctcagcct cccgagttgt 4020 tgggattcca ggcatgcatg accaggctca gctaattttt gtttttttgg tagagacggg 4080 gtttcaccat attggccagg ctggtctcca actcctaatc tcaggtgatc tacccacctt 4140 ggcctcccaa attgctggga ttacaggcgt gaaccactgc tcccttccct gtccttctga 4200 ttttgtaggt aaccacgtgc ggaccgagcg gccgcaggaa cccctagtga tggagttggc 4260 cactccctct ctgcgcgctc gctcgctcac tgaggccggg cgaccaaagg tcgcccgacg 4320 cccgggcttt gcccgggcgg cctcagtgag cgagcgagcg cgcagctgcc tgcaggggcg 4380 cctgatgcgg tattttctcc ttacgcatct gtgcggtatt tcacaccgca tacgtcgtag 4440 ctgatcaatt ggcgcgccga attcgttaac aagctttaat taacgcgtat acctaggatc 4500 cggccggcct gcaggtgtcc tcacaggaac gaagtcccta aagaaacagt ggcagccagg 4560 tttagccccg gaattgactg gattcctttt ttagggccca ttggtatggc tttttccccg 4620 tatcccccca ggtgtctgca ggctcaaaga gcagcgagaa gcgttcagag gaaagcgatc 4680 ccgtgccacc ttccccgtgc ccgggctgtc cccgcacgct gccggctcgg ggatgcgggg 4740 ggagcgccgg accggagcgg agccccgggc ggctcgctgc tgccccctag cgggggaggg 4800 acgtaattac atccctgggg gctttggggg ggggctgtcc ctctagagcg gccgccaccg 4860 cggtggagct ccagcttttg ttccctttag tgagggttaa ttagatctta atacgactca 4920 ctatagggcg aattgggtac cgggcccccc ctcgaggtcg acggtatcga taagcttgat 4980 atctataaca agaaaatata tatataataa gttatcacgt aagtagaaca tgaaataaca 5040 atataattat cgtatgagtt aaatcttaaa agtcacgtaa aagataatca tgcgtcattt 5100 tgactcacgc ggtcgttata gttcaaaatc agtgacactt accgcattga caagcacgcc 5160 tcacgggagc tccaagcggc gactgagatg tcctaaatgc acagcgacgg attcgcgcta 5220 tttagaaaga gagagcaata tttcaagaat gcatgcgtca attttacgca gactatcttt 5280 ctagggttaa tctagctgca tcaggatcat atcgtcgggt cttttttccg gctcagtcat 5340 cgcccaagct ggcgctatct gggcatcggg gaggaagaag cccgtgcctt ttcccgcgag 5400 gttgaagcgg catggaaaga gtttgccgag gatgactgct gctgcattga cgttgagcga 5460 aaacgcacgt ttaccatgat gattcgggaa ggtgtggcca tgcacgcctt taacggtgaa 5520 ctgttcgttc aggccacctg ggataccagt tcgtcgcggc ttttccggac acagttccgg 5580 atggtcagcc cgaagcgcat cagcaacccg aacaataccg gcgacagccg gaactgccgt 5640 gccggtgtgc agattaatga cagcggtgcg gcgctgggat attacgtcag cgaggacggg 5700 tatcctggct ggatgccgca gaaatggaca tggatacccc gtgagttacc cggcgggcgc 5760 gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc 5820 cacacaacat acgagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgagct 5880 aactcacatt aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc 5940 agctgcatta atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt 6000 ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag 6060 ctcactcaaa ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca 6120 tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt 6180 tccataggct ccgcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc 6240 gaaacccgac aggactataa agataccagg cgtttccccc tggaagctcc ctcgtgcgct 6300 ctcctgttcc gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg 6360 tggcgctttc tcatagctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca 6420 agctgggctg tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact 6480 atcgtcttga gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta 6540 acaggattag cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta 6600 actacggcta cactagaagg acagtatttg gtatctgcgc tctgctgaag ccagttacct 6660 tcggaaaaag agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt 6720 tttttgtttg caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga 6780 tcttttctac ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca 6840 tgagattatc aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat 6900 caatctaaag tatatatgag taaacttggt ctgacagtta ccaatgctta atcagtgagg 6960 cacctatctc agcgatctgt ctatttcgtt catccatagt tgcctgactc cccgtcgtgt 7020 agataactac gatacgggag ggcttaccat ctggccccag tgctgcaatg ataccgcgag 7080 acccacgctc accggctcca gatttatcag caataaacca gccagccgga agggccgagc 7140 gcagaagtgg tcctgcaact ttatccgcct ccatccagtc tattaattgt tgccgggaag 7200 ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt tgttgccatt gctacaggca 7260 tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag ctccggttcc caacgatcaa 7320 ggcgagttac atgatccccc atgttgtgca aaaaagcggt tagctccttc ggtcctccga 7380 tcgttgtcag aagtaagttg gccgcagtgt tatcactcat ggttatggca gcactgcata 7440 attctcttac tgtcatgcca tccgtaagat gcttttctgt gactggtgag tactcaacca 7500 agtcattctg agaatagtgt atgcggcgac cgagttgctc ttgcccggcg tcaatacggg 7560 ataataccgc gccacatagc agaactttaa aagtgctcat cattggaaaa cgttcttcgg 7620 ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg 7680 cacccaactg atcttcagca tcttttactt tcaccagcgt ttctgggtga gcaaaaacag 7740 gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg gaaatgttga atactcat 7798 <210> 28 <211> 9399 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 28 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcttaagcgc tgatcaattg gcgcgccgaa ttcgttatct 1560 gcagaattcg gcttggcggc tgcgcgttca aacctcccgc ttcaaaatgg agaccctgcg 1620 tgctcactcg ggcttaaata cccagcgtga ccacatggtg tcgcaaaatg tcgcaaaaca 1680 ctcacgtgac ctctaataca ggacctctag agcatggaaa ctagataaga aagaaatacg 1740 cagagaccaa agttcaactg aaacgaatta aacggtttat tgattaacaa gcaaactagt 1800 ttacagatta cgggtgaggt aacgggtgcc aatggggcgg ggttcagagt acacgccttc 1860 tgtattaaca gcaaagtcca cacttgtaga tttgtagtag ttggaggtgt actggatctc 1920 ggggttccag cgcttgctgt tttccttctg cagctcccat tcaatttcca cgctgacctg 1980 tccggtgctg tattgcgtga tgaaagagtt cagctttgac tggttgaagg tggtcggagg 2040 atccgcaggt acaggcgtgt tcttgatcag gatctgaggc ggaggatgtt tcaggccaaa 2100 gccgcccatc agcggagacg ggtggaagtt gccgtccgtg tgaggaatct tggcccagat 2160 gggaccctgc aggtacacgt cccggttctg ccagaccata ccgggtaagg ccccctggct 2220 gttgacagtt ccaatttgag gagccgtgtt ttgctgctgc aagttatctg ccacgatacc 2280 gtattcctct gtagccacag ggttagtggt tttgatttct tcctcgctgg tgagcatgac 2340 atcgctgtaa tccgcattgt ctctggcagc attttgtttg ccaaaaatca ggatcccgtt 2400 actgggaaaa aaacgctcct cgtcgtcttt gtgtgttgcc atagcgatgc caggattagc 2460 caatgaattt cttccattca gatggtattt ggtcccagca gtccaggcaa agttgctatt 2520 gttgttttgc ccggttgtcg ttgagacgcg ttgttggcgg taacagggtc ctggcagcca 2580 gttctttgcc tgattggcca ttgtattagg cccaccttgg ctgaagccca gagtctgcgt 2640 atttgccgtg cctcctgttg tttgagtccg agacaagtag tacaggtact ggtcaatcag 2700 aggattcatc agccggtcca agctctggct gtgggcgtag ctgctgtgga aaggcacgtc 2760 ctcgaaggtg taagtaaact ggaagttgtt gccggttctc agcatctgcg aaggaaagta 2820 ttccaggcag tagaaggagg agcgtcccac ggcctgacta ccgttgttga gtgttaggta 2880 gccgtactgg ggaatcatga acacgtccgc cgggaacgga ggcaggcagc cctggtgggc 2940 agagccgaga acgtacggca gctggtactc cgagtccgta aacacctgga tggtgctggt 3000 gaggttattg gcgatggtct tggtgccttc attctgcgtg acctccttga cctggatgtt 3060 gaagagcttg aagctgagtc tcttgggccg gaatccccag ttgttgttga tgagtcgctg 3120 ccagtcacgt ggtgaaaagt ggcagtggaa tctgttaaag tcaaaatacc cccagggggt 3180 gctgtagccg aagtaggtgt tgtcgttggt ggctcctccc gatgtcccgt tggagatttg 3240 cttgtagagg tggttgttgt aggtgggcag ggcccaggtt cgggtgctgg tggtgatgac 3300 tctgtcgccc agccatgtgg aatcgcaatg ccaatttccc gaggaactac ccactccgtc 3360 ggcgccttcg ttattgtctg ccattggtgc gccaccgcct gcagccattg tattaggtcc 3420 cacaccagag ggcgctgctg gaggttctcc gagaggttga gggtctggaa ctgactctga 3480 gtcgccagtc tgaccaaaat tgagtctttt tctggcgggc tgttggcctt tcttgccgat 3540 gcccgtagag gagtctggag aacgctgggg tgatggctct accggtctct tctttccagg 3600 agccgtctta gcgccttcct caaccagacc gagaggttcg agaacccgct tcttggcctg 3660 gaagactgct cgcccgaggt tgcccccaaa agacgtatct tcttgcagac gctcctgaaa 3720 ctcggcgtcg gcgtggttat accgcaggta cggattgtca cccgcctgca gctgctggtc 3780 gtaggccttg tcgtgctcga gggccgctgc gtccgccgcg ttgacgggct cccccttgtc 3840 gagtccgttg aagggtccga ggtacttgta gccaggaagc accagacccc ggccgtcgtc 3900 ctgcttttgc tggttggctt tgggcttcgg ggctccaggt ttcagcgccc accactcgcg 3960 aatgccctca gagaggttgt cctcgagcca atctggaaga taaccatcgg cagccatacc 4020 tgatttaaat catttattgt tcaaagatgc agtcatccaa atccacattg accagatcgc 4080 aggcagtgca agcgtctggc acctttccca tgatatgatg aatgtagcac agtttctgat 4140 acgccttttt gacgacagaa acgggttgag attctgacac gggaaagcac tctaaacagt 4200 ctttctgtcc gtgagtgaag cagatatttg aattctgatt cattctctcg cattgtctgc 4260 agggaaacag catcagattc atgcccacgt gacgagaaca tttgttttgg tacctgtctg 4320 cgtagttgat cgaagcttcc gcgtctgacg tcgatggctg cgcaactgac tcgcgcaccc 4380 gtttgggctc acttatatct gcgtcactgg gggcgggtct tttcttggct ccaccctttt 4440 tgacgtagaa ttcatgctcc acctcaacca cgtgatcctt tgcccaccgg aaaaagtctt 4500 tgacttcctg cttggtgacc ttcccaaagt catgatccag acggcgggtg agttcaaatt 4560 tgaacatccg gtcttgcaac ggctgctggt gttcgaaggt cgttgagttc ccgtcaatca 4620 cggcgcacat gttggtgttg gaggtgacga tcacgggagt cgggtctatc tgggccgagg 4680 acttgcattt ctggtccacg cgcaccttgc ttcctccgag aatggctttg gccgactcca 4740 cgaccttggc ggtcatcttc ccctcctccc accagatcac catcttgtcg acacagtcgt 4800 tgaagggaaa gttctcattg gtccagttta cgcacccgta gaagggcaca gtgtgggcta 4860 tggcctccgc gatgttggtc ttcccggtag ttgcaggccc aaacagccag atggtgttcc 4920 tcttgccgaa ctttttcgtg gcccatccca gaaagacgga agccgcatat tggggatcgt 4980 acccgtttag ttccaaaatt ttataaatcc gattgctgga aatgtcctcc acgggctgct 5040 ggcccaccag gtagtcgggg gcggttttag tcaggctcat aatctttccc gcattgtcca 5100 aggcagcctt gatttgggac cgcgagttgg aggccgcatt gaaggagatg tatgaggcct 5160 ggtcctcctg gatccactgc ttctccgagg taatcccctt gtccacgagc cacccgacca 5220 gctccatgta cctggctgaa gtttttgatc tgatcaccgg cgcatcagaa ttgggattct 5280 gattctcttt gttctgctcc tgcgtctgcg acacgtgcgt cagatgctgc gccaccaacc 5340 gtttacgctc cgtgagattc aaacaggcgc tgtggagaga aaggcaaagt ggatgtcagt 5400 atctctatca ctgataggga gatctctatc actgataggg aacttacctt aaatactgtt 5460 ccatattagt ccacgcccac tggagctcag gctgggtttt ggggagcaag taattgggga 5520 tgtagcactc atccaccacc ttgttcccgc ctccggcgcc atttctggtc tttgtgaccg 5580 cgaaccagtt tggcaaagtc ggctcgatcc cgcggtaaat tctctgaatc agtttttcgc 5640 gaatctgact caggaaacgt cccaaaacca tggatttcac cccggtggtt tccacgagca 5700 cgtgcatgtg gaagtagctc tctcccttct caaattgcac aaagaaaaga gcctccgggg 5760 ccttactcac acggcgccat tccgtcagaa agtcgcgctg cagcttctcg gccacggtca 5820 ggggtgcctg ctcaatcaga ttcagatcca tgtcagaatc tggcggcaac tcccattcct 5880 tctcggccac ccagttcaca aagctgtcag aaatgccggg cagatgctcg tcaaggtcgc 5940 tggggacctt aatcacaatc tcgtaaaacc ccggcatggc ggctgcgcgt tcaaacctcc 6000 cgcttcaaaa tggagaccct gcgtgctcac tcgggcgatc tctatcactg atagggagat 6060 ctctatcact gatagggaga ttaaatagaa tggctaggat ccggccggcc tgcaggtgtc 6120 ctcacaggaa cgaagtccct aaagaaacag tggcagccag gtttagcccc ggaattgact 6180 ggattccttt tttagggccc attggtatgg ctttttcccc gtatcccccc aggtgtctgc 6240 aggctcaaag agcagcgaga agcgttcaga ggaaagcgat cccgtgccac cttccccgtg 6300 cccgggctgt ccccgcacgc tgccggctcg gggatgcggg gggagcgccg gaccggagcg 6360 gagccccggg cggctcgctg ctgcccccta gcgggggagg gacgtaatta catccctggg 6420 ggctttgggg gggggctgtc cctctagagc ggccgccacc gcggtggagc tccagctttt 6480 gttcccttta gtgagggtta attagatctt aatacgactc actatagggc gaattgggta 6540 ccgggccccc cctcgaggtc gacggtatcg ataagcttga tatctataac aagaaaatat 6600 atatataata agttatcacg taagtagaac atgaaataac aatataatta tcgtatgagt 6660 taaatcttaa aagtcacgta aaagataatc atgcgtcatt ttgactcacg cggtcgttat 6720 agttcaaaat cagtgacact taccgcattg acaagcacgc ctcacgggag ctccaagcgg 6780 cgactgagat gtcctaaatg cacagcgacg gattcgcgct atttagaaag agagagcaat 6840 atttcaagaa tgcatgcgtc aattttacgc agactatctt tctagggtta atctagctgc 6900 atcaggatca tatcgtcggg tcttttttcc ggctcagtca tcgcccaagc tggcgctatc 6960 tgggcatcgg ggaggaagaa gcccgtgcct tttcccgcga ggttgaagcg gcatggaaag 7020 agtttgccga ggatgactgc tgctgcattg acgttgagcg aaaacgcacg tttaccatga 7080 tgattcggga aggtgtggcc atgcacgcct ttaacggtga actgttcgtt caggccacct 7140 gggataccag ttcgtcgcgg cttttccgga cacagttccg gatggtcagc ccgaagcgca 7200 tcagcaaccc gaacaatacc ggcgacagcc ggaactgccg tgccggtgtg cagattaatg 7260 acagcggtgc ggcgctggga tattacgtca gcgaggacgg gtatcctggc tggatgccgc 7320 agaaatggac atggataccc cgtgagttac ccggcgggcg cgcttggcgt aatcatggtc 7380 atagctgttt cctgtgtgaa attgttatcc gctcacaatt ccacacaaca tacgagccgg 7440 aagcataaag tgtaaagcct ggggtgccta atgagtgagc taactcacat taattgcgtt 7500 gcgctcactg cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt aatgaatcgg 7560 ccaacgcgcg gggagaggcg gtttgcgtat tgggcgctct tccgcttcct cgctcactga 7620 ctcgctgcgc tcggtcgttc ggctgcggcg agcggtatca gctcactcaa aggcggtaat 7680 acggttatcc acagaatcag gggataacgc aggaaagaac atgtgagcaa aaggccagca 7740 aaaggccagg aaccgtaaaa aggccgcgtt gctggcgttt ttccataggc tccgcccccc 7800 tgacgagcat cacaaaaatc gacgctcaag tcagaggtgg cgaaacccga caggactata 7860 aagataccag gcgtttcccc ctggaagctc cctcgtgcgc tctcctgttc cgaccctgcc 7920 gcttaccgga tacctgtccg cctttctccc ttcgggaagc gtggcgcttt ctcatagctc 7980 acgctgtagg tatctcagtt cggtgtaggt cgttcgctcc aagctgggct gtgtgcacga 8040 accccccgtt cagcccgacc gctgcgcctt atccggtaac tatcgtcttg agtccaaccc 8100 ggtaagacac gacttatcgc cactggcagc agccactggt aacaggatta gcagagcgag 8160 gtatgtaggc ggtgctacag agttcttgaa gtggtggcct aactacggct acactagaag 8220 gacagtattt ggtatctgcg ctctgctgaa gccagttacc ttcggaaaaa gagttggtag 8280 ctcttgatcc ggcaaacaaa ccaccgctgg tagcggtggt ttttttgttt gcaagcagca 8340 gattacgcgc agaaaaaaag gatctcaaga agatcctttg atcttttcta cggggtctga 8400 cgctcagtgg aacgaaaact cacgttaagg gattttggtc atgagattat caaaaaggat 8460 cttcacctag atccttttaa attaaaaatg aagttttaaa tcaatctaaa gtatatatga 8520 gtaaacttgg tctgacagtt accaatgctt aatcagtgag gcacctatct cagcgatctg 8580 tctatttcgt tcatccatag ttgcctgact ccccgtcgtg tagataacta cgatacggga 8640 gggcttacca tctggcccca gtgctgcaat gataccgcga gacccacgct caccggctcc 8700 agatttatca gcaataaacc agccagccgg aagggccgag cgcagaagtg gtcctgcaac 8760 tttatccgcc tccatccagt ctattaattg ttgccgggaa gctagagtaa gtagttcgcc 8820 agttaatagt ttgcgcaacg ttgttgccat tgctacaggc atcgtggtgt cacgctcgtc 8880 gtttggtatg gcttcattca gctccggttc ccaacgatca aggcgagtta catgatcccc 8940 catgttgtgc aaaaaagcgg ttagctcctt cggtcctccg atcgttgtca gaagtaagtt 9000 ggccgcagtg ttatcactca tggttatggc agcactgcat aattctctta ctgtcatgcc 9060 atccgtaaga tgcttttctg tgactggtga gtactcaacc aagtcattct gagaatagtg 9120 tatgcggcga ccgagttgct cttgcccggc gtcaatacgg gataataccg cgccacatag 9180 cagaacttta aaagtgctca tcattggaaa acgttcttcg gggcgaaaac tctcaaggat 9240 cttaccgctg ttgagatcca gttcgatgta acccactcgt gcacccaact gatcttcagc 9300 atcttttact ttcaccagcg tttctgggtg agcaaaaaca ggaaggcaaa atgccgcaaa 9360 aaagggaata agggcgacac ggaaatgttg aatactcat 9399 <210> 29 <211> 9393 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 29 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcttaagcgc tgatcaattg gcgcgccgaa ttcgttatct 1560 gcagaattcg gcttggcggc tgcgcgttca aacctcccgc ttcaaaatgg agaccctgcg 1620 tgctcactcg ggcttaaata cccagcgtga ccacatggtg tcgcaaaatg tcgcaaaaca 1680 ctcacgtgac ctctaataca ggacctctag agcatggaaa ctagataaga aagaaatacg 1740 cagagaccaa agttcaactg aaacgaatta aacggtttat tgattaacaa gcaaactagt 1800 ttacagatta cgagtcaggt atctggtgcc aatggggcgg ggttcactat atacaccttc 1860 agtattaaca gcaaattcaa cattattaga cttgtaatag ttggaagtgt actggatctc 1920 cgggttccag cgcttgctgt tttccttctg cagctcccac tcgatctcca cgctgacttg 1980 gccagtagaa tactgggtga tgaaagagtt cagcttgtcc ttgttgaagg ccgttggagg 2040 atccgcaggt acaggtgtgt ttttgatgag gatctgagga ggcgggtgct tcattccaaa 2100 ccctcccatc agcggagaag ggtgaaagtt gccgtccgtg tgaggaattt tggcccaaat 2160 gggtccttgc aggtacacat ctctgtcctg ccaaaccata cccggaagta ttccttggtt 2220 ttgaacccag ccggtctgcg cctgtgcttg ggcactctgg tggtttgtgg ccacttgtcc 2280 ataggactcc gttgctaccg ggttagtagt tttaatttct tcttcgttgg ttatcatgac 2340 tttgtccgca tccacgttgt ctcttccagt tccttgtttg ccaaaaatta aagatccaga 2400 caaaggaaag aaacggtcct ctccttcttt gtggctggcc atagcaggtc caggattcat 2460 caagctatta cgtccattga gagcccaaga agaagctcca ggccaagcaa attcgctgtt 2520 gttgttttga gtcacagtgg ttgagacacg ttgttgtcgg tagctgggtc caggtatgta 2580 gtttcttccc tggacagcca tgttgctggg tccggccaca ctgaatttta gcgtttgttg 2640 attctgtcca gaaccgttaa tagtctttga gagatagtac aagtattggt cgatgagtgg 2700 attcattagt cggtccaggc tttggctgtg agcgtagctg ctatggaaag gtacgttctc 2760 aaactcgtag ctgaactgga agttgttacc cgttcttagc atttgcgacg ggaaatattc 2820 caggcagtaa aaggacgaac gacccacggc ctggcttcca tcattaagcg tcagataccc 2880 gtactgagga atcatgaaaa cgtccgctgg gaacggcggg aggcagccct cgtgagccga 2940 cccgagcacg tacgggagct gatagtctga gtccgtgaag acctggaccg tgctggtaag 3000 gttattggcg atggtcttga ctccattgtt gtccgtaacc tctttgacct gaatgttgaa 3060 gagcttgaag ttgagtcgct taggccggaa tccccagttg ttgttgatga gtcgctgcca 3120 gtcacgtggt gagaagtggc agtggaatct gttgaagtca aaataccccc agggggtgct 3180 gtagccgaag taggcgttgt catttgaaga tcctccagat gtgctgttgg agatttgctt 3240 gtagaggtga ttgttgtagg tgggcagggc ccaggttcgg gtgctggtgg tgatgactct 3300 gtcccccagc cattgggaat cgcaatgcca atttcccgag gaactaccca ctccatcggc 3360 accttcgtta ttgtctgcca ctggtgcgcc accacctgaa gccattgtaa gagatcccac 3420 acctgagggg gctgcgggag gttctccgat tggttgaggg tctgggactg actctgtgtc 3480 gccagtctga ccgaaattga gtctcttttt agcgggctgt gcacccgatt tgccaatacc 3540 cgcggaggag tccggttcct gaggagactg ctctacaggc ctcttctttc caggagccgt 3600 cttagccgct tcctcaacca gaccaagagg ttcaagaagc ctctttttgg cctggaagac 3660 tgctcgcccg aggttgcccc caaaagacgt atcttctttg agccgctcct ggaactcggc 3720 gtcggcgtgg ttgtacttga ggtacgggtt gtctccggcc ttgagctgct ggtcgtaggc 3780 cttgtcgtgc tcgagggccg ccgcgtctgc tgcgttgacc ggctccccct tgtcgagtcc 3840 gttgccgggt ccaaggtatt tgtaacccgg aagcacaaga cctcgagcgt tgtcttgatg 3900 ttgttgattt gccttgggtt gaggggctcc aggtttcaaa gcccaccact cgcgaattcc 3960 ttcactaagg ttgtcctcga gccaatctgg aagataacca tcggcagcca tacctgattt 4020 aaatcattta ttgttcaaag atgcagtcat ccaaatccac attgaccaga tcgcaggcag 4080 tgcaagcgtc tggcaccttt cccatgatat gatgaatgta gcacagtttc tgatacgcct 4140 ttttgacgac agaaacgggt tgagattctg acacgggaaa gcactctaaa cagtctttct 4200 gtccgtgagt gaagcagata tttgaattct gattcattct ctcgcattgt ctgcagggaa 4260 acagcatcag attcatgccc acgtgacgag aacatttgtt ttggtacctg tctgcgtagt 4320 tgatcgaagc ttccgcgtct gacgtcgatg gctgcgcaac tgactcgcgc acccgtttgg 4380 gctcacttat atctgcgtca ctgggggcgg gtcttttctt ggctccaccc tttttgacgt 4440 agaattcatg ctccacctca accacgtgat cctttgccca ccggaaaaag tctttgactt 4500 cctgcttggt gaccttccca aagtcatgat ccagacggcg ggtgagttca aatttgaaca 4560 tccggtcttg caacggctgc tggtgttcga aggtcgttga gttcccgtca atcacggcgc 4620 acatgttggt gttggaggtg acgatcacgg gagtcgggtc tatctgggcc gaggacttgc 4680 atttctggtc cacgcgcacc ttgcttcctc cgagaatggc tttggccgac tccacgacct 4740 tggcggtcat cttcccctcc tcccaccaga tcaccatctt gtcgacacag tcgttgaagg 4800 gaaagttctc attggtccag tttacgcacc cgtagaaggg cacagtgtgg gctatggcct 4860 ccgcgatgtt ggtcttcccg gtagttgcag gcccaaacag ccagatggtg ttcctcttgc 4920 cgaacttttt cgtggcccat cccagaaaga cggaagccgc atattgggga tcgtacccgt 4980 ttagttccaa aattttataa atccgattgc tggaaatgtc ctccacgggc tgctggccca 5040 ccaggtagtc gggggcggtt ttagtcaggc tcataatctt tcccgcattg tccaaggcag 5100 ccttgatttg ggaccgcgag ttggaggccg cattgaagga gatgtatgag gcctggtcct 5160 cctggatcca ctgcttctcc gaggtaatcc ccttgtccac gagccacccg accagctcca 5220 tgtacctggc tgaagttttt gatctgatca ccggcgcatc agaattggga ttctgattct 5280 ctttgttctg ctcctgcgtc tgcgacacgt gcgtcagatg ctgcgccacc aaccgtttac 5340 gctccgtgag attcaaacag gcgctgtgga gagaaaggca aagtggatgt cagtatctct 5400 atcactgata gggagatctc tatcactgat agggaactta ccttaaatac tgttccatat 5460 tagtccacgc ccactggagc tcaggctggg ttttggggag caagtaattg gggatgtagc 5520 actcatccac caccttgttc ccgcctccgg cgccatttct ggtctttgtg accgcgaacc 5580 agtttggcaa agtcggctcg atcccgcggt aaattctctg aatcagtttt tcgcgaatct 5640 gactcaggaa acgtcccaaa accatggatt tcaccccggt ggtttccacg agcacgtgca 5700 tgtggaagta gctctctccc ttctcaaatt gcacaaagaa aagagcctcc ggggccttac 5760 tcacacggcg ccattccgtc agaaagtcgc gctgcagctt ctcggccacg gtcaggggtg 5820 cctgctcaat cagattcaga tccatgtcag aatctggcgg caactcccat tccttctcgg 5880 ccacccagtt cacaaagctg tcagaaatgc cgggcagatg ctcgtcaagg tcgctgggga 5940 ccttaatcac aatctcgtaa aaccccggca tggcggctgc gcgttcaaac ctcccgcttc 6000 aaaatggaga ccctgcgtgc tcactcgggc gatctctatc actgataggg agatctctat 6060 cactgatagg gagattaaat agaatggcta ggatccggcc ggcctgcagg tgtcctcaca 6120 ggaacgaagt ccctaaagaa acagtggcag ccaggtttag ccccggaatt gactggattc 6180 cttttttagg gcccattggt atggcttttt ccccgtatcc ccccaggtgt ctgcaggctc 6240 aaagagcagc gagaagcgtt cagaggaaag cgatcccgtg ccaccttccc cgtgcccggg 6300 ctgtccccgc acgctgccgg ctcggggatg cggggggagc gccggaccgg agcggagccc 6360 cgggcggctc gctgctgccc cctagcgggg gagggacgta attacatccc tgggggcttt 6420 gggggggggc tgtccctcta gagcggccgc caccgcggtg gagctccagc ttttgttccc 6480 tttagtgagg gttaattaga tcttaatacg actcactata gggcgaattg ggtaccgggc 6540 cccccctcga ggtcgacggt atcgataagc ttgatatcta taacaagaaa atatatatat 6600 aataagttat cacgtaagta gaacatgaaa taacaatata attatcgtat gagttaaatc 6660 ttaaaagtca cgtaaaagat aatcatgcgt cattttgact cacgcggtcg ttatagttca 6720 aaatcagtga cacttaccgc attgacaagc acgcctcacg ggagctccaa gcggcgactg 6780 agatgtccta aatgcacagc gacggattcg cgctatttag aaagagagag caatatttca 6840 agaatgcatg cgtcaatttt acgcagacta tctttctagg gttaatctag ctgcatcagg 6900 atcatatcgt cgggtctttt ttccggctca gtcatcgccc aagctggcgc tatctgggca 6960 tcggggagga agaagcccgt gccttttccc gcgaggttga agcggcatgg aaagagtttg 7020 ccgaggatga ctgctgctgc attgacgttg agcgaaaacg cacgtttacc atgatgattc 7080 gggaaggtgt ggccatgcac gcctttaacg gtgaactgtt cgttcaggcc acctgggata 7140 ccagttcgtc gcggcttttc cggacacagt tccggatggt cagcccgaag cgcatcagca 7200 acccgaacaa taccggcgac agccggaact gccgtgccgg tgtgcagatt aatgacagcg 7260 gtgcggcgct gggatattac gtcagcgagg acgggtatcc tggctggatg ccgcagaaat 7320 ggacatggat accccgtgag ttacccggcg ggcgcgcttg gcgtaatcat ggtcatagct 7380 gtttcctgtg tgaaattgtt atccgctcac aattccacac aacatacgag ccggaagcat 7440 aaagtgtaaa gcctggggtg cctaatgagt gagctaactc acattaattg cgttgcgctc 7500 actgcccgct ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg 7560 cgcggggaga ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct 7620 gcgctcggtc gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt 7680 atccacagaa tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc 7740 caggaaccgt aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga 7800 gcatcacaaa aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata 7860 ccaggcgttt ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac 7920 cggatacctg tccgcctttc tcccttcggg aagcgtggcg ctttctcata gctcacgctg 7980 taggtatctc agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc 8040 cgttcagccc gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag 8100 acacgactta tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt 8160 aggcggtgct acagagttct tgaagtggtg gcctaactac ggctacacta gaaggacagt 8220 atttggtatc tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg 8280 atccggcaaa caaaccaccg ctggtagcgg tggttttttt gtttgcaagc agcagattac 8340 gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt tctacggggt ctgacgctca 8400 gtggaacgaa aactcacgtt aagggatttt ggtcatgaga ttatcaaaaa ggatcttcac 8460 ctagatcctt ttaaattaaa aatgaagttt taaatcaatc taaagtatat atgagtaaac 8520 ttggtctgac agttaccaat gcttaatcag tgaggcacct atctcagcga tctgtctatt 8580 tcgttcatcc atagttgcct gactccccgt cgtgtagata actacgatac gggagggctt 8640 accatctggc cccagtgctg caatgatacc gcgagaccca cgctcaccgg ctccagattt 8700 atcagcaata aaccagccag ccggaagggc cgagcgcaga agtggtcctg caactttatc 8760 cgcctccatc cagtctatta attgttgccg ggaagctaga gtaagtagtt cgccagttaa 8820 tagtttgcgc aacgttgttg ccattgctac aggcatcgtg gtgtcacgct cgtcgtttgg 8880 tatggcttca ttcagctccg gttcccaacg atcaaggcga gttacatgat cccccatgtt 8940 gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt gtcagaagta agttggccgc 9000 agtgttatca ctcatggtta tggcagcact gcataattct cttactgtca tgccatccgt 9060 aagatgcttt tctgtgactg gtgagtactc aaccaagtca ttctgagaat agtgtatgcg 9120 gcgaccgagt tgctcttgcc cggcgtcaat acgggataat accgcgccac atagcagaac 9180 tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga aaactctcaa ggatcttacc 9240 gctgttgaga tccagttcga tgtaacccac tcgtgcaccc aactgatctt cagcatcttt 9300 tactttcacc agcgtttctg ggtgagcaaa aacaggaagg caaaatgccg caaaaaaggg 9360 aataagggcg acacggaaat gttgaatact cat 9393 <210> 30 <211> 9393 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 30 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atcgaattcc tgcagcccgg gggatccact 1140 agttctagag ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg 1200 ctagggggca gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc 1260 ccgagccggc agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc 1320 ctctgaacgc ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaag 1380 gcctccaagg ccagcttccc acaataagtt gggtgaattt tggctcattc ctcctttcta 1440 taggattgag gtcagagctt tgtgatggga attctgtgga atgtgtgtca gttagggtgt 1500 ggaaagtccc gcgatcgcta gcttaagcgc tgatcaattg gcgcgccgaa ttcgttatct 1560 gcagaattcg gcttggcggc tgcgcgttca aacctcccgc ttcaaaatgg agaccctgcg 1620 tgctcactcg ggcttaaata cccagcgtga ccacatggtg tcgcaaaatg tcgcaaaaca 1680 ctcacgtgac ctctaataca ggacctctag agcatggaaa ctagataaga aagaaatacg 1740 cagagaccaa agttcaactg aaacgaatta aacggtttat tgattaacaa gcaaactagt 1800 ttacagatta cgggtgaggt aacgggtgcc gatggggcga ggctcagaat aaacgccatt 1860 tgtgtcaaca gcaaagtcca catttgtaga tttgttgtag ttggaagtgt attgaatctc 1920 tgggttccag cgtttgctgt tttctttctg cagctcccat tcaatttcca cgctgacctg 1980 tccggtgctg tactgcgtga tgaacgacgc aaacttagct ggactgaagg tagttggagg 2040 attcgcggga acaggtgtat tcttaatcag gatctgagga ggcgggtgtt tcagtccaaa 2100 gcctcccatc agcggcgagg gatgaaagtg tccgtccgtg tgaggaatct tggcccagat 2160 aggaccctgc aggtacacgt cccggtcctg ccagaccatg ccaggtaagg ctccttgact 2220 gttgacggtc cctgtagcag gagcggtgtt ggccgattgc aggttagtgg ccaccgtgcc 2280 gtactcttct gtggccactg ggttggtggt tttaatttct tcctcgttgg ttatcataac 2340 gttgtcaagg tccacgttgc tatttccagc tccctgtttc ccaaatatta agactccgct 2400 catcggaaaa aatttgtctt cgtcgtcctt gtgggttgcc atagcgggac cgggatttac 2460 cagagagtct ctgccattca gatgatactt ggtggcaccg gtccaggcaa agttgctgtt 2520 gttattttga ttggttgtct tggagacgcg ttgctgccgg tagcagggcc cgggtagcca 2580 gtttttggcc tgattcgcca tgctactagg cccggcctga gaaaattgca acgtccgatt 2640 tcctgcggta ccactcgtgg tctgagtccg agacaggtag tacaggtact ggtcgatgag 2700 ggggttcatc agccggtcca ggctttggct gtgcgcgtag ctgctgtgaa aaggcacgtc 2760 ctcaaacgtg tagctgaact gaaagttgtt gcccgttctc agcatttgag aaggaaagta 2820 ttccaggcag tagaaggagg aacggcccac ggcctgactg ccattgttca gagtcaggta 2880 cccgtactga ggaatcatga agacgtccgc cgggaacgga ggcaggcagc cctggtgcgc 2940 agagccgagg acgtacggga gctggtattc cgagtccgta aagacctgaa ccgtgctggt 3000 aaggttattg gcgatggtcg tggtgccatc attcgtcgtg acctccttga cctggatgtt 3060 gaagagcttg aagttgagct tcttgggccg gaatccccag ttgttgttga tgagtcgctg 3120 ccagtcacgt ggtgagaagt ggcagtggaa tctgttaaag tcaaaatacc cccagggggt 3180 gctgtagccg aagtaggtgt tgtcgttggt gctgcctccc gattggctgg agatttgctt 3240 gtagaggtgg ttgttgtagg tggggagggc ccaggttcgg gtgctggtgg tgatgactct 3300 gtcgcccagc catgtggaat cgcaatgcca atttcctgag gcgttaccca ctccgtcggc 3360 gccttcgtta ttgtctgcca ttggagcgcc accgcctgca gccattgtat tagatcccac 3420 accagagggg gctgcggggg gttctccgag tggttgaggg tcgggcactg actctgagtc 3480 gccagtctgc ccaaagttga gtctctttct cgcgggctgc tggcctttct tgccgatgcc 3540 cgaagaggag tctggttcct ggggtgattg ctctaccggt ctcttctttc caggagccgt 3600 cttagcgcct tcctcaacca gaccgagagg ttcgagaacc cgcttcttgg cctggaagac 3660 tgctcgcccg aggttgcccc caaaagacgt atcttcttgc agacgctcct gaaactcggc 3720 gtcggcgtgg ttataccgca ggtacggatt gtcacccgct ttgagctgct ggtcgtaggc 3780 cttgtcgtgc tcgagggccg ctgcgtccgc cgcgttgacg ggctccccct tgtcgagtcc 3840 gttgaagggt ccgaggtact tgtagccagg aagcaccaga ccccggccgt cgtcctgctt 3900 ttgctggttg gctttgggtt tcggggctcc aggtttcaag tcccaccact cgcgaatgcc 3960 ctcagagagg ttgtcctcga gccaatctgg aagataacca tcggcagcca tacctgattt 4020 aaatcattta ttgttcaaag atgcagtcat ccaaatccac attgaccaga tcgcaggcag 4080 tgcaagcgtc tggcaccttt cccatgatat gatgaatgta gcacagtttc tgatacgcct 4140 ttttgacgac agaaacgggt tgagattctg acacgggaaa gcactctaaa cagtctttct 4200 gtccgtgagt gaagcagata tttgaattct gattcattct ctcgcattgt ctgcagggaa 4260 acagcatcag attcatgccc acgtgacgag aacatttgtt ttggtacctg tctgcgtagt 4320 tgatcgaagc ttccgcgtct gacgtcgatg gctgcgcaac tgactcgcgc acccgtttgg 4380 gctcacttat atctgcgtca ctgggggcgg gtcttttctt ggctccaccc tttttgacgt 4440 agaattcatg ctccacctca accacgtgat cctttgccca ccggaaaaag tctttgactt 4500 cctgcttggt gaccttccca aagtcatgat ccagacggcg ggtgagttca aatttgaaca 4560 tccggtcttg caacggctgc tggtgttcga aggtcgttga gttcccgtca atcacggcgc 4620 acatgttggt gttggaggtg acgatcacgg gagtcgggtc tatctgggcc gaggacttgc 4680 atttctggtc cacgcgcacc ttgcttcctc cgagaatggc tttggccgac tccacgacct 4740 tggcggtcat cttcccctcc tcccaccaga tcaccatctt gtcgacacag tcgttgaagg 4800 gaaagttctc attggtccag tttacgcacc cgtagaaggg cacagtgtgg gctatggcct 4860 ccgcgatgtt ggtcttcccg gtagttgcag gcccaaacag ccagatggtg ttcctcttgc 4920 cgaacttttt cgtggcccat cccagaaaga cggaagccgc atattgggga tcgtacccgt 4980 ttagttccaa aattttataa atccgattgc tggaaatgtc ctccacgggc tgctggccca 5040 ccaggtagtc gggggcggtt ttagtcaggc tcataatctt tcccgcattg tccaaggcag 5100 ccttgatttg ggaccgcgag ttggaggccg cattgaagga gatgtatgag gcctggtcct 5160 cctggatcca ctgcttctcc gaggtaatcc ccttgtccac gagccacccg accagctcca 5220 tgtacctggc tgaagttttt gatctgatca ccggcgcatc agaattggga ttctgattct 5280 ctttgttctg ctcctgcgtc tgcgacacgt gcgtcagatg ctgcgccacc aaccgtttac 5340 gctccgtgag attcaaacag gcgctgtgga gagaaaggca aagtggatgt cagtatctct 5400 atcactgata gggagatctc tatcactgat agggaactta ccttaaatac tgttccatat 5460 tagtccacgc ccactggagc tcaggctggg ttttggggag caagtaattg gggatgtagc 5520 actcatccac caccttgttc ccgcctccgg cgccatttct ggtctttgtg accgcgaacc 5580 agtttggcaa agtcggctcg atcccgcggt aaattctctg aatcagtttt tcgcgaatct 5640 gactcaggaa acgtcccaaa accatggatt tcaccccggt ggtttccacg agcacgtgca 5700 tgtggaagta gctctctccc ttctcaaatt gcacaaagaa aagagcctcc ggggccttac 5760 tcacacggcg ccattccgtc agaaagtcgc gctgcagctt ctcggccacg gtcaggggtg 5820 cctgctcaat cagattcaga tccatgtcag aatctggcgg caactcccat tccttctcgg 5880 ccacccagtt cacaaagctg tcagaaatgc cgggcagatg ctcgtcaagg tcgctgggga 5940 ccttaatcac aatctcgtaa aaccccggca tggcggctgc gcgttcaaac ctcccgcttc 6000 aaaatggaga ccctgcgtgc tcactcgggc gatctctatc actgataggg agatctctat 6060 cactgatagg gagattaaat agaatggcta ggatccggcc ggcctgcagg tgtcctcaca 6120 ggaacgaagt ccctaaagaa acagtggcag ccaggtttag ccccggaatt gactggattc 6180 cttttttagg gcccattggt atggcttttt ccccgtatcc ccccaggtgt ctgcaggctc 6240 aaagagcagc gagaagcgtt cagaggaaag cgatcccgtg ccaccttccc cgtgcccggg 6300 ctgtccccgc acgctgccgg ctcggggatg cggggggagc gccggaccgg agcggagccc 6360 cgggcggctc gctgctgccc cctagcgggg gagggacgta attacatccc tgggggcttt 6420 gggggggggc tgtccctcta gagcggccgc caccgcggtg gagctccagc ttttgttccc 6480 tttagtgagg gttaattaga tcttaatacg actcactata gggcgaattg ggtaccgggc 6540 cccccctcga ggtcgacggt atcgataagc ttgatatcta taacaagaaa atatatatat 6600 aataagttat cacgtaagta gaacatgaaa taacaatata attatcgtat gagttaaatc 6660 ttaaaagtca cgtaaaagat aatcatgcgt cattttgact cacgcggtcg ttatagttca 6720 aaatcagtga cacttaccgc attgacaagc acgcctcacg ggagctccaa gcggcgactg 6780 agatgtccta aatgcacagc gacggattcg cgctatttag aaagagagag caatatttca 6840 agaatgcatg cgtcaatttt acgcagacta tctttctagg gttaatctag ctgcatcagg 6900 atcatatcgt cgggtctttt ttccggctca gtcatcgccc aagctggcgc tatctgggca 6960 tcggggagga agaagcccgt gccttttccc gcgaggttga agcggcatgg aaagagtttg 7020 ccgaggatga ctgctgctgc attgacgttg agcgaaaacg cacgtttacc atgatgattc 7080 gggaaggtgt ggccatgcac gcctttaacg gtgaactgtt cgttcaggcc acctgggata 7140 ccagttcgtc gcggcttttc cggacacagt tccggatggt cagcccgaag cgcatcagca 7200 acccgaacaa taccggcgac agccggaact gccgtgccgg tgtgcagatt aatgacagcg 7260 gtgcggcgct gggatattac gtcagcgagg acgggtatcc tggctggatg ccgcagaaat 7320 ggacatggat accccgtgag ttacccggcg ggcgcgcttg gcgtaatcat ggtcatagct 7380 gtttcctgtg tgaaattgtt atccgctcac aattccacac aacatacgag ccggaagcat 7440 aaagtgtaaa gcctggggtg cctaatgagt gagctaactc acattaattg cgttgcgctc 7500 actgcccgct ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg 7560 cgcggggaga ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct 7620 gcgctcggtc gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt 7680 atccacagaa tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc 7740 caggaaccgt aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga 7800 gcatcacaaa aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata 7860 ccaggcgttt ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac 7920 cggatacctg tccgcctttc tcccttcggg aagcgtggcg ctttctcata gctcacgctg 7980 taggtatctc agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc 8040 cgttcagccc gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag 8100 acacgactta tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt 8160 aggcggtgct acagagttct tgaagtggtg gcctaactac ggctacacta gaaggacagt 8220 atttggtatc tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg 8280 atccggcaaa caaaccaccg ctggtagcgg tggttttttt gtttgcaagc agcagattac 8340 gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt tctacggggt ctgacgctca 8400 gtggaacgaa aactcacgtt aagggatttt ggtcatgaga ttatcaaaaa ggatcttcac 8460 ctagatcctt ttaaattaaa aatgaagttt taaatcaatc taaagtatat atgagtaaac 8520 ttggtctgac agttaccaat gcttaatcag tgaggcacct atctcagcga tctgtctatt 8580 tcgttcatcc atagttgcct gactccccgt cgtgtagata actacgatac gggagggctt 8640 accatctggc cccagtgctg caatgatacc gcgagaccca cgctcaccgg ctccagattt 8700 atcagcaata aaccagccag ccggaagggc cgagcgcaga agtggtcctg caactttatc 8760 cgcctccatc cagtctatta attgttgccg ggaagctaga gtaagtagtt cgccagttaa 8820 tagtttgcgc aacgttgttg ccattgctac aggcatcgtg gtgtcacgct cgtcgtttgg 8880 tatggcttca ttcagctccg gttcccaacg atcaaggcga gttacatgat cccccatgtt 8940 gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt gtcagaagta agttggccgc 9000 agtgttatca ctcatggtta tggcagcact gcataattct cttactgtca tgccatccgt 9060 aagatgcttt tctgtgactg gtgagtactc aaccaagtca ttctgagaat agtgtatgcg 9120 gcgaccgagt tgctcttgcc cggcgtcaat acgggataat accgcgccac atagcagaac 9180 tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga aaactctcaa ggatcttacc 9240 gctgttgaga tccagttcga tgtaacccac tcgtgcaccc aactgatctt cagcatcttt 9300 tactttcacc agcgtttctg ggtgagcaaa aacaggaagg caaaatgccg caaaaaaggg 9360 aataagggcg acacggaaat gttgaatact cat 9393 <210> 31 <211> 7147 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 31 gacggatcgg gagatctgag ctcacgggga cagccccccc ccaaagcccc cagggatgta 60 attacgtccc tcccccgcta gggggcagca gcgagccgcc cggggctccg ctccggtccg 120 gcgctccccc cgcatccccg agccggcagc gtgcggggac agcccgggca cggggaaggt 180 ggcacgggat cgctttcctc tgaacgcttc tcgctgctct ttgagcctgc agacacctgg 240 ggggatacgg ggaaaaagct ttaggctgaa agagagattt agaatgacag aatcatagaa 300 cggcctgggt tgcaaaggag cacagtgctc atccagatcc aaccccctgc tatgtgcagg 360 gtcatcaacc agcagcccag gctgcccaga gccacatcca gcctggcctt gaatgcctgc 420 aggcccgatc ccctatggtc gactctcagt acaatctgct ctgatgccgc atagttaagc 480 cagtatctgc tccctgcttg tgtgttggag gtcgctgagt agtgcgcgag caaaatttaa 540 gctacaacaa ggcaaggctt gaccgacaat tgcatgaaga atctgcttag ggttaggcgt 600 tttgcgctgc ttcgcgatgt acgggccaga tatacgcgtt gacattgatt attgactagt 660 tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga gttccgcgtt 720 acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg cccattgacg 780 tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg acgtcaatgg 840 gtggactatt tacggtaaac tgcccacttg gcagtacatc aagtgtatca tatgccaagt 900 acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct ggcattatgc ccagtacatg 960 accttatggg actttcctac ttggcagtac atctacgtat tagtcatcgc tattaccatg 1020 gtgatgcggt tttggcagta catcaatggg cgtggatagc ggtttgactc acggggattt 1080 ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac 1140 tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg 1200 tgggaggtct atataagcag agctctctgg ctaactagag aacccactgc ttactggctt 1260 atcgaaatta atacgactca ctatagggag acccaagctg gctagcgttt aaacttaagc 1320 tttctgtgag tttggggacc cttgattgtt ctttcttttt cgctattgta aaattcatgt 1380 tatatggagg gggcaaagtt ttcagggtgt tgtttagaat gggaagatgt cccttgtatc 1440 accatggacc ctcatgataa ttttgtttct ttcactttct actctgttga caaccattgt 1500 ctcctcttat tttcttttca ttttctgtaa ctttttcgtt aaactttagc ttgcatttgt 1560 aacgaatttt taaattcact tttgtttatt tgtcagattg taagtacttt ctctaatcac 1620 ttttttttca aggcaatcag ggtatattat attgtacttc agcacagttt tagagaacaa 1680 ttgttataat taaatgataa ggtagaatat ttctgcatat aaattctggc tggcgtggaa 1740 atattcttat tggtagaaac aactacatcc tggtcatcat cctgcctttc tctttatggt 1800 tacaatgata tacactgttt gagatgagga taaaatactc tgagtccaaa ccgggcccct 1860 ctgctaacca tgttcatgcc ttcttctttt tcctacagct cctgggcaac gtgctggtta 1920 ttgtgctgtc tcatcatttt ggcaaagaat tgtaatacga ctcactatag ggcgagccac 1980 catggctaga ttagataaaa gtaaagtgat taacagcgca ttagagctgc ttaatgaggt 2040 cggaatcgaa ggtttaacaa cccgtaaact cgcccagaag ctaggtgtag agcagcctac 2100 attgtattgg catgtaaaaa ataagcgggc tttgctcgac gccttagcca ttgagatgtt 2160 agataggcac catactcact tttgcccttt agaaggggaa agctggcaag attttttacg 2220 taataacgct aaaagtttta gatgtgcttt actaagtcat cgcgatggag caaaagtaca 2280 tttaggtaca cggcctacag aaaaacagta tgaaactctc gaaaatcaat tagccttttt 2340 atgccaacaa ggtttttcac tagagaatgc cttatatgca ctcagcgccg tggggcattt 2400 tactttaggt tgcgtattgg aagatcaaga gcatcaagtc gctaaagaag aaagggaaac 2460 acctactact gatagtatgc cgccattatt acgacaagct atcgaattat ttgatcacca 2520 aggtgcagag ccagccttct tattcggcct tgaattgatc atatgcggat tagaaaaaca 2580 acttaaatgt gaaagtgggt ccccaaaaaa gaagagaaag gtcgacggcg gtggttcagt 2640 ttaagcgtac agcgggatcc actagtccag tgtggtggaa ttctgcagat atccagcaca 2700 gtggcggccg ctcgagtcta gagggcccgt ttaaacccgc tgatcagcct cgactgtgcc 2760 ttctagttgc cagccatctg ttgtttgccc ctcccccgtg ccttccttga ccctggaagg 2820 tgccactccc actgtccttt cctaataaaa tgaggaaatt gcatcgcatt gtctgagtag 2880 gtgtcattct attctggggg gtggggtggg gcaggacagc aagggggagg attgggaaga 2940 caatagcagg catgctgggg atgcggtggg ctctatggct tctgaggcgg aaagaaccag 3000 ctggggctct agggggtatc cccacgcgcc ctgtagcggc gcattaagcg cggcgggtgt 3060 ggtggttacg cgcagcgtga ccgctacact tgccagcgcc ctagcgcccg ctcctttcgc 3120 tttcttccct tcctttctcg ccacgttcgc cggctttccc cgtcaagctc taaatcgggg 3180 catcccttta gggttccgat ttagtgcttt acggcacctc gaccccaaaa aacttgatta 3240 gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg gtttttcgcc ctttgacgtt 3300 ggagtccacg ttctttaata gtggactctt gttccaaact ggaacaacac tcaaccctat 3360 ctcggtctat tcttttgatt tataagggat tttggggatt tcggcctatt ggttaaaaaa 3420 tgagctgatt taacaaaaat ttaacgcgaa ttaattctgt ggaatgtgtg tcagttaggg 3480 tgtggaaagt ccccaggctc cccaggcagg cagaagtatg caaagcatgc atctcaatta 3540 gtcagcaacc aggtgtggaa agtccccagg ctccccagca ggcagaagta tgcaaagcat 3600 gcatctcaat tagtcagcaa ccatagtccc gcccctaact ccgcccatcc cgcccctaac 3660 tccgcccagt tccgcccatt ctccgcccca tggctgacta atttttttta tttatgcaga 3720 ggccgaggcc gcctctgcct ctgagctatt ccagaagtag tgaggaggct tttttggagg 3780 cctaggcttt tgcaaaaagc tcccgggagc ttgtatatcc attttcggat ctgatcagca 3840 cgtgttgaca attaatcatc ggcatagtat atcggcatag tataatacga caaggtgagg 3900 aactaaacca tggccaagtt gaccagtgcc gttccggtgc tcaccgcgcg cgacgtcgcc 3960 ggagcggtcg agttctggac cgaccggctc gggttctccc gggacttcgt ggaggacgac 4020 ttcgccggtg tggtccggga cgacgtgacc ctgttcatca gcgcggtcca ggaccaggtg 4080 gtgccggaca acaccctggc ctgggtgtgg gtgcgcggcc tggacgagct gtacgccgag 4140 tggtcggagg tcgtgtccac gaacttccgg gacgcctccg ggccggccat gaccgagatc 4200 ggcgagcagc cgtgggggcg ggagttcgcc ctgcgcgacc cggccggcaa ctgcgtgcac 4260 ttcgtggccg aggagcagga ctgacacgtg ctacgagatt tcgattccac cgccgccttc 4320 tatgaaaggt tgggcttcgg aatcgttttc cgggacgccg gctggatgat cctccagcgc 4380 ggggatctca tgctggagtt cttcgcccac cccaacttgt ttattgcagc ttataatggt 4440 tacaaataaa gcaatagcat cacaaatttc acaaataaag catttttttc actgcattct 4500 agttgtggtt tgtccaaact catcaatgta tcttatcatg tctgtatacc gtcgacctct 4560 agctagagct tggcgtaatc atggtcatag ctgtttcctg tgtgaaattg ttatccgctc 4620 acaattccac acaacatacg agccggaagc ataaagtgta aagcctgggg tgcctaatga 4680 gtgagctaac tcacattaat tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg 4740 tcgtgccagc tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg 4800 cgctcttccg cttcctcgct cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg 4860 gtatcagctc actcaaaggc ggtaatacgg ttatccacag aatcagggga taacgcagga 4920 aagagagctc acggggacag ccccccccca aagcccccag ggatgtaatt acgtccctcc 4980 cccgctaggg ggcagcagcg agccgcccgg ggctccgctc cggtccggcg ctccccccgc 5040 atccccgagc cggcagcgtg cggggacagc ccgggcacgg ggaaggtggc acgggatcgc 5100 tttcctctga acgcttctcg ctgctctttg agcctgcaga cacctggggg gatacgggga 5160 aaaagcttta ggctgaaaga gagatttaga atgacagaat catagaacgg cctgggttgc 5220 aaaggagcac agtgctcatc cagatccaac cccctgctat gtgcagggtc atcaaccagc 5280 agcccaggct gcccagagcc acatccagcc tggccttgaa tgcctgcagg acatgtgagc 5340 aaaaggccag caaaaggcca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 5400 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 5460 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 5520 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 5580 ttctcaatgc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 5640 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 5700 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 5760 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 5820 ctacactaga aggacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 5880 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 5940 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 6000 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 6060 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 6120 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 6180 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 6240 tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc gagacccacg 6300 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 6360 tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg aagctagagt 6420 aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc attgctacag gcatcgtggt 6480 gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 6540 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 6600 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 6660 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 6720 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatac 6780 cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 6840 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 6900 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 6960 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 7020 ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat acatatttga 7080 atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa aagtgccacc 7140 tgacgtc 7147 <210> 32 <211> 7493 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 32 gacggatcgg gagatctgag ctcacgggga cagccccccc ccaaagcccc cagggatgta 60 attacgtccc tcccccgcta gggggcagca gcgagccgcc cggggctccg ctccggtccg 120 gcgctccccc cgcatccccg agccggcagc gtgcggggac agcccgggca cggggaaggt 180 ggcacgggat cgctttcctc tgaacgcttc tcgctgctct ttgagcctgc agacacctgg 240 ggggatacgg ggaaaaagct ttaggctgaa agagagattt agaatgacag aatcatagaa 300 cggcctgggt tgcaaaggag cacagtgctc atccagatcc aaccccctgc tatgtgcagg 360 gtcatcaacc agcagcccag gctgcccaga gccacatcca gcctggcctt gaatgcctgc 420 aggcccgatc ccctatggtc gactctcagt acaatctgct ctgatgccgc atagttaagc 480 cagtatctgc tccctgcttg tgtgttggag gtcgctgagt agtgcgcgag caaaatttaa 540 gctacaacaa ggcaaggctt gaccgacaat tgcatgaaga atctgcttag ggttaggcgt 600 tttgcgctgc ttcgcgatgt acgggccaga tatacgcgtt gacattgatt attgactagt 660 tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga gttccgcgtt 720 acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg cccattgacg 780 tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg acgtcaatgg 840 gtggactatt tacggtaaac tgcccacttg gcagtacatc aagtgtatca tatgccaagt 900 acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct ggcattatgc ccagtacatg 960 accttatggg actttcctac ttggcagtac atctacgtat tagtcatcgc tattaccatg 1020 gtgatgcggt tttggcagta catcaatggg cgtggatagc ggtttgactc acggggattt 1080 ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac 1140 tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg 1200 tgggaggtct atataagcag agctctctgg ctaactagag aacccactgc ttactggctt 1260 atcgaaatta atacgactca ctatagggag acccaagctg gctagcgttt aaacttaagc 1320 tttctgtgag tttggggacc cttgattgtt ctttcttttt cgctattgta aaattcatgt 1380 tatatggagg gggcaaagtt ttcagggtgt tgtttagaat gggaagatgt cccttgtatc 1440 accatggacc ctcatgataa ttttgtttct ttcactttct actctgttga caaccattgt 1500 ctcctcttat tttcttttca ttttctgtaa ctttttcgtt aaactttagc ttgcatttgt 1560 aacgaatttt taaattcact tttgtttatt tgtcagattg taagtacttt ctctaatcac 1620 ttttttttca aggcaatcag ggtatattat attgtacttc agcacagttt tagagaacaa 1680 ttgttataat taaatgataa ggtagaatat ttctgcatat aaattctggc tggcgtggaa 1740 atattcttat tggtagaaac aactacatcc tggtcatcat cctgcctttc tctttatggt 1800 tacaatgata tacactgttt gagatgagga taaaatactc tgagtccaaa ccgggcccct 1860 ctgctaacca tgttcatgcc ttcttctttt tcctacagct cctgggcaac gtgctggtta 1920 ttgtgctgtc tcatcatttt ggcaaagaat tgtaatacga ctcactatag ggcgagccac 1980 catggctaga ttagataaaa gtaaagtgat taacagcgca ttagagctgc ttaatgaggt 2040 cggaatcgaa ggtttaacaa cccgtaaact cgcccagaag ctaggtgtag agcagcctac 2100 attgtattgg catgtaaaaa ataagcgggc tttgctcgac gccttagcca ttgagatgtt 2160 agataggcac catactcact tttgcccttt agaaggggaa agctggcaag attttttacg 2220 taataacgct aaaagtttta gatgtgcttt actaagtcat cgcgatggag caaaagtaca 2280 tttaggtaca cggcctacag aaaaacagta tgaaactctc gaaaatcaat tagccttttt 2340 atgccaacaa ggtttttcac tagagaatgc cttatatgca ctcagcgccg tggggcattt 2400 tactttaggt tgcgtattgg aagatcaaga gcatcaagtc gctaaagaag aaagggaaac 2460 acctactact gatagtatgc cgccattatt acgacaagct atcgaattat ttgatcacca 2520 aggtgcagag ccagccttct tattcggcct tgaattgatc atatgcggat tagaaaaaca 2580 acttaaatgt gaaagtgggt ccccaaaaaa gaagagaaag gtcgacggcg gtggtgcttt 2640 gtctcctcag cactctgctg tcactcaagg aagtatcatc aagaacaagg agggcatgga 2700 tgctaagtca ctaactgcct ggtcccggac actggtgacc ttcaaggatg tatttgtgga 2760 cttcaccagg gaggagtgga agctgctgga cactgctcag cagatcgtgt acagaaatgt 2820 gatgctggag aactataaga acctggtttc cttgggttat cagcttacta agccagatgt 2880 gatcctccgg ttggagaagg gagaagagcc ctggctggtg gagagagaaa ttcaccaaga 2940 gacccatcct gattcagaga ctgcatttga aatcaaatca tcagtttaag cgtacagcgg 3000 ggatccacta gtccagtgtg gtggaattct gcagatatcc agcacagtgg cggccgctcg 3060 agtctagagg gcccgtttaa acccgctgat cagcctcgac tgtgccttct agttgccagc 3120 catctgttgt ttgcccctcc cccgtgcctt ccttgaccct ggaaggtgcc actcccactg 3180 tcctttccta ataaaatgag gaaattgcat cgcattgtct gagtaggtgt cattctattc 3240 tggggggtgg ggtggggcag gacagcaagg gggaggattg ggaagacaat agcaggcatg 3300 ctggggatgc ggtgggctct atggcttctg aggcggaaag aaccagctgg ggctctaggg 3360 ggtatcccca cgcgccctgt agcggcgcat taagcgcggc gggtgtggtg gttacgcgca 3420 gcgtgaccgc tacacttgcc agcgccctag cgcccgctcc tttcgctttc ttcccttcct 3480 ttctcgccac gttcgccggc tttccccgtc aagctctaaa tcggggcatc cctttagggt 3540 tccgatttag tgctttacgg cacctcgacc ccaaaaaact tgattagggt gatggttcac 3600 gtagtgggcc atcgccctga tagacggttt ttcgcccttt gacgttggag tccacgttct 3660 ttaatagtgg actcttgttc caaactggaa caacactcaa ccctatctcg gtctattctt 3720 ttgatttata agggattttg gggatttcgg cctattggtt aaaaaatgag ctgatttaac 3780 aaaaatttaa cgcgaattaa ttctgtggaa tgtgtgtcag ttagggtgtg gaaagtcccc 3840 aggctcccca ggcaggcaga agtatgcaaa gcatgcatct caattagtca gcaaccaggt 3900 gtggaaagtc cccaggctcc ccagcaggca gaagtatgca aagcatgcat ctcaattagt 3960 cagcaaccat agtcccgccc ctaactccgc ccatcccgcc cctaactccg cccagttccg 4020 cccattctcc gccccatggc tgactaattt tttttattta tgcagaggcc gaggccgcct 4080 ctgcctctga gctattccag aagtagtgag gaggcttttt tggaggccta ggcttttgca 4140 aaaagctccc gggagcttgt atatccattt tcggatctga tcagcacgtg ttgacaatta 4200 atcatcggca tagtatatcg gcatagtata atacgacaag gtgaggaact aaaccatggc 4260 caagttgacc agtgccgttc cggtgctcac cgcgcgcgac gtcgccggag cggtcgagtt 4320 ctggaccgac cggctcgggt tctcccggga cttcgtggag gacgacttcg ccggtgtggt 4380 ccgggacgac gtgaccctgt tcatcagcgc ggtccaggac caggtggtgc cggacaacac 4440 cctggcctgg gtgtgggtgc gcggcctgga cgagctgtac gccgagtggt cggaggtcgt 4500 gtccacgaac ttccgggacg cctccgggcc ggccatgacc gagatcggcg agcagccgtg 4560 ggggcgggag ttcgccctgc gcgacccggc cggcaactgc gtgcacttcg tggccgagga 4620 gcaggactga cacgtgctac gagatttcga ttccaccgcc gccttctatg aaaggttggg 4680 cttcggaatc gttttccggg acgccggctg gatgatcctc cagcgcgggg atctcatgct 4740 ggagttcttc gcccacccca acttgtttat tgcagcttat aatggttaca aataaagcaa 4800 tagcatcaca aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc 4860 caaactcatc aatgtatctt atcatgtctg tataccgtcg acctctagct agagcttggc 4920 gtaatcatgg tcatagctgt ttcctgtgtg aaattgttat ccgctcacaa ttccacacaa 4980 catacgagcc ggaagcataa agtgtaaagc ctggggtgcc taatgagtga gctaactcac 5040 attaattgcg ttgcgctcac tgcccgcttt ccagtcggga aacctgtcgt gccagctgca 5100 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 5160 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 5220 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga gagctcacgg 5280 ggacagcccc cccccaaagc ccccagggat gtaattacgt ccctcccccg ctagggggca 5340 gcagcgagcc gcccggggct ccgctccggt ccggcgctcc ccccgcatcc ccgagccggc 5400 agcgtgcggg gacagcccgg gcacggggaa ggtggcacgg gatcgctttc ctctgaacgc 5460 ttctcgctgc tctttgagcc tgcagacacc tggggggata cggggaaaaa gctttaggct 5520 gaaagagaga tttagaatga cagaatcata gaacggcctg ggttgcaaag gagcacagtg 5580 ctcatccaga tccaaccccc tgctatgtgc agggtcatca accagcagcc caggctgccc 5640 agagccacat ccagcctggc cttgaatgcc tgcaggacat gtgagcaaaa ggccagcaaa 5700 aggccaggaa ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg 5760 acgagcatca caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa 5820 gataccaggc gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc 5880 ttaccggata cctgtccgcc tttctccctt cgggaagcgt ggcgctttct caatgctcac 5940 gctgtaggta tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac 6000 cccccgttca gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg 6060 taagacacga cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt 6120 atgtaggcgg tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagga 6180 cagtatttgg tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct 6240 cttgatccgg caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga 6300 ttacgcgcag aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg 6360 ctcagtggaa cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct 6420 tcacctagat ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt 6480 aaacttggtc tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc 6540 tatttcgttc atccatagtt gcctgactcc ccgtcgtgta gataactacg atacgggagg 6600 gcttaccatc tggccccagt gctgcaatga taccgcgaga cccacgctca ccggctccag 6660 atttatcagc aataaaccag ccagccggaa gggccgagcg cagaagtggt cctgcaactt 6720 tatccgcctc catccagtct attaattgtt gccgggaagc tagagtaagt agttcgccag 6780 ttaatagttt gcgcaacgtt gttgccattg ctacaggcat cgtggtgtca cgctcgtcgt 6840 ttggtatggc ttcattcagc tccggttccc aacgatcaag gcgagttaca tgatccccca 6900 tgttgtgcaa aaaagcggtt agctccttcg gtcctccgat cgttgtcaga agtaagttgg 6960 ccgcagtgtt atcactcatg gttatggcag cactgcataa ttctcttact gtcatgccat 7020 ccgtaagatg cttttctgtg actggtgagt actcaaccaa gtcattctga gaatagtgta 7080 tgcggcgacc gagttgctct tgcccggcgt caatacggga taataccgcg ccacatagca 7140 gaactttaaa agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct 7200 taccgctgtt gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat 7260 cttttacttt caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa 7320 agggaataag ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt 7380 gaagcattta tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa 7440 ataaacaaat aggggttccg cgcacatttc cccgaaaagt gccacctgac gtc 7493

Claims (107)

  1. 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포로서,
    a. 제1 탈억제 가능한 프로모터의 제어하에 바이러스 헬퍼 유전자를 암호화하는 핵산 분자;
    b. 제2 탈억제 가능한 프로모터의 제어하에 AAV 유전자를 암호화하는 핵산 분자; 및
    c. 제1 및 제2 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 핵산 분자를 포함하는 포유동물 세포.
  2. 제1항에 있어서, 상기 포유동물 세포는 포유동물 세포 배양물인 포유동물 세포.
  3. 제2항에 있어서, 상기 포유동물 세포 배양물은 현탁 배양물인 포유동물 세포.
  4. 제1항 내지 제3항 중 어느 한 항에 있어서, 상기 바이러스 헬퍼 유전자는 아데노바이러스 헬퍼 유전자인 포유동물 세포.
  5. 제4항에 있어서, 상기 아데노바이러스 헬퍼 유전자는 E2A 및 E4Orf6 유전자를 포함하는 포유동물 세포.
  6. 제5항에 있어서, 상기 E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함하는 포유동물 세포.
  7. 제1항 내지 제6항 중 어느 한 항에 있어서, 상기 AAV 유전자는 Rep 및 Cap 유전자를 포함하는 포유동물 세포.
  8. 제7항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제3 탈억제 가능한 프로모터의 제어하에 있는 포유동물 세포.
  9. 제7항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제3 탈억제 가능한 프로모터의 제어하에 있는 포유동물 세포.
  10. 제8항 또는 제9항에 있어서, 상기 Cap 유전자는 고유 프로모터의 제어하에 있는 포유동물 세포.
  11. 제1항 내지 제10항 중 어느 한 항에 있어서, 상기 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함하는 포유동물 세포.
  12. 제11항에 있어서, 상기 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터인 포유동물 세포.
  13. 제1항 내지 제12항 중 어느 한 항에 있어서, 상기 억제자 요소는 구성적 프로모터의 제어하에 있는 포유동물 세포.
  14. 제1항 내지 제13항 중 어느 한 항에 있어서, 상기 억제자 요소는 테트라사이클린 억제자 단백질인 포유동물 세포.
  15. 제14항에 있어서, 상기 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함하는 포유동물 세포.
  16. 제1항 내지 제15항 중 어느 한 항에 있어서, 상기 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포인 포유동물 세포.
  17. 제1항 내지 제15항 중 어느 한 항에 있어서, 상기 포유동물 세포는 인간 세포인 포유동물 세포.
  18. 제17항에 있어서, 상기 인간 세포는 인간 배아 신장 (HEK) 세포인 포유동물 세포.
  19. 제1항 내지 제18항 중 어느 한 항에 있어서, 2개의 역위 말단 반복 (ITR) 서열을 포함하는 핵산 분자를 추가로 포함하는 포유동물 세포.
  20. 제1항 내지 제19항 중 어느 한 항에 있어서, 관심 유전자를 암호화하는 핵산 분자를 추가로 포함하는 포유동물 세포.
  21. 제1항 내지 제20항 중 어느 한 항에 있어서, 제4 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA를 암호화하는 핵산을 추가로 포함하는 포유동물 세포.
  22. 아데노 관련 바이러스 (AAV)를 생산하기 위한 포유동물 세포로서,
    a. 핵산 분자로서,
    i. 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자;
    ii. 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자;
    iii. 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA;
    iv. 2개의 역위 말단 반복 (ITR) 서열; 및
    v. 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는, 상기 핵산 분자를 포함하는, 포유동물 세포.
  23. 제22항에 있어서, 상기 포유동물 세포는 포유동물 세포 배양물인 포유동물 세포.
  24. 제23항에 있어서, 상기 포유동물 세포 배양물은 현탁 배양물인 포유동물 세포.
  25. 제22항 내지 제24항 중 어느 한 항에 있어서, 상기 E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함하는 포유동물 세포.
  26. 제22항 내지 제25항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있는 포유동물 세포.
  27. 제22항 내지 제25항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있는 포유동물 세포.
  28. 제26항 또는 제27항에 있어서, 상기 Cap 유전자는 고유 프로모터의 제어하에 있는 포유동물 세포.
  29. 제22항 내지 제28항 중 어느 한 항에 있어서, 상기 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함하는 포유동물 세포.
  30. 제29항에 있어서, 상기 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터인 포유동물 세포.
  31. 제22항 내지 제30항 중 어느 한 항에 있어서, 상기 억제자 요소는 구성적 프로모터의 제어하에 있는 포유동물 세포.
  32. 제22항 내지 제31항 중 어느 한 항에 있어서, 상기 억제자 요소는 테트라사이클린 억제자 단백질인 포유동물 세포.
  33. 제25항에 있어서, 상기 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함하는 포유동물 세포.
  34. 제22항 내지 제33항 중 어느 한 항에 있어서, 상기 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포인 포유동물 세포.
  35. 제22항 내지 제33항 중 어느 한 항에 있어서, 상기 포유동물 세포는 인간 세포인 포유동물 세포.
  36. 제35항에 있어서, 상기 인간 세포는 인간 배아 신장 (HEK) 세포인 포유동물 세포.
  37. 제22항 내지 제36항 중 어느 한 항에 있어서, 관심 유전자를 암호화하는 핵산 분자를 추가로 포함하는 포유동물 세포.
  38. 단리된 핵산 분자로서,
    a. 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자;
    b. 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자;
    c. 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA;
    d. 2개의 역위 말단 반복 (ITR) 서열; 및
    e. 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소를 암호화하는 단리된 핵산 분자.
  39. 제38항에 있어서, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함하는 단리된 핵산.
  40. 제38항 내지 제39항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있는 단리된 핵산.
  41. 제38항 내지 제39항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있는 단리된 핵산.
  42. 제40항 또는 제41항에 있어서, 상기 Cap 유전자는 고유 프로모터의 제어하에 있는 단리된 핵산.
  43. 제38항 내지 제42항 중 어느 한 항에 있어서, 상기 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함하는 단리된 핵산.
  44. 제43항에 있어서, 상기 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터인 단리된 핵산.
  45. 제38항 내지 제44항 중 어느 한 항에 있어서, 상기 억제자 요소는 구성적 프로모터의 제어하에 있는 단리된 핵산.
  46. 제38항 내지 제45항 중 어느 한 항에 있어서, 상기 억제자 요소는 테트라사이클린 억제자 단백질인 단리된 핵산.
  47. 제46항에 있어서, 상기 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함하는 단리된 핵산.
  48. 제38항 내지 제47항 중 어느 한 항에 있어서, 관심 유전자를 추가로 포함하는 단리된 핵산.
  49. 포유동물 세포에서 아데노 관련 바이러스 (AAV)를 생산하는 방법으로서,
    a. 포유동물 세포를 하기를 암호화하는 단리된 핵산 분자로 형질 감염시키는 단계:
    i. 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자;
    ii. 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자;
    iii. 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA;
    iv. 2개의 역위 말단 반복 (ITR) 서열; 및
    v. 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소;
    b. 포유동물 세포를 억제자 요소의 결합 파트너로 처리하는 단계;
    c. 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화시키는 단계;
    d. AAV를 생산하는 단계; 및
    e. AAV를 수확하는 단계를 포함하는, 방법.
  50. 제49항에 있어서, 상기 포유동물 세포는 포유동물 세포 배양물인 방법.
  51. 제50항에 있어서, 상기 포유동물 세포 배양물은 현탁 배양물인 방법.
  52. 제49항 내지 제51항 중 어느 한 항에 있어서, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함하는 방법.
  53. 제49항 내지 제52항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있는 방법.
  54. 제49항 내지 제52항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있는 방법.
  55. 제54항에 있어서, 상기 제4 탈억제 가능한 프로모터는 탈억제 가능한 프로모터를 활성화한 후 AAV를 생산하기 전에 제거되는 방법.
  56. 제53항 또는 제54항에 있어서, 상기 Cap 유전자는 고유 프로모터의 제어하에 있는 방법.
  57. 제49항 내지 제56항 중 어느 한 항에 있어서, 상기 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함하는 방법.
  58. 제57항에 있어서, 상기 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터인 방법.
  59. 제49항 내지 제58항 중 어느 한 항에 있어서, 상기 억제자 요소는 구성적 프로모터의 제어하에 있는 방법.
  60. 제49항 내지 제59항 중 어느 한 항에 있어서, 상기 억제자 요소는 테트라사이클린 억제자 단백질인 방법.
  61. 제60항에 있어서, 상기 핵산은 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함하는 방법.
  62. 제60항 또는 제61항에 있어서, 상기 처리는 독시사이클린으로 처리하는 것을 포함하는 방법.
  63. 제49항 내지 제62항 중 어느 한 항에 있어서, 상기 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포인 방법.
  64. 제49항 내지 제63항 중 어느 한 항에 있어서, 상기 포유동물 세포는 인간 세포인 방법.
  65. 제64항에 있어서, 상기 인간 세포는 인간 배아 신장 (HEK) 세포인 방법.
  66. 제49항 내지 제65항 중 어느 한 항에 있어서, 상기 AAV는 관심 유전자를 암호화하는 핵산 분자를 포함하는 방법.
  67. 제66항에 있어서, 상기 AAV는 치료적 관심 유전자를 포함하는 방법.
  68. 아데노 관련 바이러스 (AAV)를 치료하는 방법으로서,
    a. 포유동물 세포를 하기를 암호화하는 단리된 핵산 분자로 형질 감염시키는 단계:
    i. 제1 탈억제 가능한 프로모터의 제어하에 E2A 및 E4Orf6 유전자를 포함하는 아데노바이러스 헬퍼 유전자;
    ii. 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자;
    iii. 제3 탈억제 가능한 프로모터의 제어하에 바이러스 관련, 비코딩 RNA;
    iv. 2개의 역위 말단 반복 (ITR) 서열; 및
    v. 제1, 제2 및 제3 탈억제 가능한 프로모터의 억제자 요소;
    b. 포유동물 세포를 억제자 요소의 결합 파트너로 처리하는 단계;
    c. 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화시키는 단계;
    d. AAV를 생산하는 단계;
    e. AAV를 수확하는 단계; 및
    f. AAV를 포유동물 환자에 투여하는 단계를 포함하는 방법.
  69. 제68항에 있어서, 상기 포유동물 세포는 포유동물 세포 배양물인 방법.
  70. 제69항에 있어서, 상기 포유동물 세포 배양물은 현탁 배양물인 방법.
  71. 제68항 내지 제70항 중 어느 한 항에 있어서, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함하는 방법.
  72. 제68항 내지 제71항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 제4 탈억제 가능한 프로모터의 제어하에 있는 방법.
  73. 제68항 내지 제72항 중 어느 한 항에 있어서, 상기 Rep78 유전자는 제2 탈억제 가능한 프로모터의 제어하에 있고 Rep52 유전자는 인공 인트론 내에 함유된 제4 탈억제 가능한 프로모터의 제어하에 있는 방법.
  74. 제73항에 있어서, 상기 제4 탈억제 가능한 프로모터는 탈억제 가능한 프로모터를 활성화한 후 AAV를 생산하기 전에 제거되는 방법,
  75. 제73항 또는 제74항에 있어서, 상기 Cap 유전자는 고유 프로모터의 제어하에 있는 방법.
  76. 제68항 내지 제75항 중 어느 한 항에 있어서, 상기 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함하는 방법.
  77. 제76항에 있어서, 상기 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터인 방법.
  78. 제68항 내지 제77항 중 어느 한 항에 있어서, 상기 억제자 요소는 구성적 프로모터의 제어하에 있는 방법.
  79. 제68항 내지 제78항 중 어느 한 항에 있어서, 상기 억제자 요소는 테트라사이클린 억제자 단백질인 방법.
  80. 제79항에 있어서, 상기 핵산은 테트라사이클린 억제자 단백질을 암호화하는 핵산과 프레임에 있는 전사 억제 도메인을 암호화하는 핵산을 추가로 포함하는 방법.
  81. 제79항 또는 제80항에 있어서, 상기 처리는 독시사이클린으로 처리하는 것을 포함하는 방법.
  82. 제68항 내지 제81항 중 어느 한 항에 있어서, 상기 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포인 방법.
  83. 제68항 내지 제82항 중 어느 한 항에 있어서, 상기 포유동물 세포는 인간 세포인 방법.
  84. 제83항에 있어서, 상기 인간 세포는 인간 배아 신장 (HEK) 세포인 방법.
  85. 제68항 내지 제84항 중 어느 한 항에 있어서, 상기 AAV는 관심 유전자를 암호화하는 핵산 분자를 포함하는 방법.
  86. 제85항에 있어서, 상기 AAV는 치료적 관심 유전자를 포함하는 방법.
  87. 제68항 내지 제86항 중 어느 한 항에 있어서, 상기 투여는 흡입, 주사 또는 정맥 내 투여를 포함하는 방법.
  88. 아데노 관련 바이러스 (AAV)를 생산하는 방법으로서,
    a. 하기로 TetR 및/또는 TetR-KRAB을 암호화하는 하나 이상의 핵산을 안정적으로 발현하는 포유동물 세포를 형질 감염시키는 단계:
    i. 제1 탈억제 가능한 프로모터의 제어하에, E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산;
    ii. 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자를 암호화하는 제2 핵산; 및
    iii. 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산;
    b. 포유동물 세포를 TetR의 결합 파트너로 처리하는 단계;
    c. 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화시키는 단계;
    d. AAV를 생산하는 단계; 및
    e. AAV를 수확하는 단계를 포함하는 방법.
  89. 제88항에 있어서, 상기 포유동물 세포는 포유동물 세포 배양물인 방법.
  90. 제88항 내지 제89항 중 어느 한 항에 있어서, 상기 포유동물 세포는 차이니즈 햄스터 난소 (CHO) 세포인 방법.
  91. 제88항 내지 제90항 중 어느 한 항에 있어서, 상기 포유동물 세포는 인간 세포인 방법.
  92. 제91항에 있어서, 상기 인간 세포는 인간 배아 신장 (HEK) 세포인 방법.
  93. 제89항에 있어서, 상기 포유동물 세포 배양물은 현탁 배양물인 방법.
  94. 제88항 내지 제90항 중 어느 한 항에 있어서, E2A와 E4Orf6 유전자 사이에 내부 리보솜 진입 부위 (IRES) 요소를 추가로 포함하는 방법.
  95. 제88항 내지 제91항 중 어느 한 항에 있어서, 상기 각각의 탈억제 가능한 프로모터는 기능적 프로모터 및 2개의 테트라사이클린 작동자 서열 (TetO2)을 포함하는 방법.
  96. 제95항에 있어서, 상기 제1 탈억제 가능한 프로모터의 기능적 프로모터는 거대세포바이러스 (CMV) 프로모터인 방법.
  97. 제88항 내지 제96항 중 어느 한 항에 있어서, 상기 TetR 및/또는 TetR-KRAB은 구성적 프로모터의 제어하에 있는 방법.
  98. 제97항에 있어서, 상기 TetR-KRAB을 암호화하는 핵산은 TetR과 프레임에 융합된 KRAB을 포함하는 방법.
  99. 제88항 내지 제98항 중 어느 한 항에 있어서, 상기 처리는 독시사이클린으로 처리하는 것을 포함하는 방법.
  100. 제88항 내지 제99항 중 어느 한 항에 있어서, 상기 각각의 제1, 제2 및 제3 핵산은 트랜스포존-특이적 역위 말단 반복 (ITR)이 측면에 있는 방법.
  101. 제88항 내지 제100항 중 어느 한 항에 있어서, 상기 포유동물 세포는 충분한 양의 TetR 및/또는 TetR-KRAB을 발현하는 방법.
  102. 제88항 내지 제101항 중 어느 한 항에 있어서, 상기 AAV는 치료적 관심 유전자를 포함하는 방법.
  103. 제88항 내지 제102항 중 어느 한 항에 있어서, 상기 포유동물 세포는 TetR 및/또는 TetR-KRAB 억제자 서열 측면에 있는 닭 과민성 부위-4 (cHS4)를 암호화하는 하나 이상의 핵산의 안정한 발현을 추가로 포함하는 방법.
  104. 제88항 내지 제103항 중 어느 한 항에 있어서, 상기 포유동물 세포는 선별 유전자를 추가로 포함하는 방법.
  105. 아데노 관련 바이러스 (AAV)를 생산하는 방법으로서,
    a. 하기로 포유동물 세포를 안정적으로 형질 감염시키는 단계:
    TetR 및/또는 TetR-KRAB 억제자를 암호화하는 핵산;
    TetR 및/또는 TetR-KRAB 억제자 측면에 있는 닭 과민성 부위-4 (cHS4) 서열; 및
    선별 유전자;
    b. 하기로 안정적으로 형질 감염된 포유동물 세포를 형질 감염시키는 단계:
    i. 제1 탈억제 가능한 프로모터의 제어하에, E2A 유전자, E4Orf 유전자 및 바이러스 관련 비코딩 RNA를 포함하는 아데노바이러스 헬퍼 유전자를 암호화하는 제1 핵산;
    ii. 제2 탈억제 가능한 프로모터의 제어하에 Rep 및 Cap 유전자를 포함하는 AAV 유전자를 암호화하는 제2 핵산; 및
    iii. 선별적으로, 제3 탈억제 가능한 프로모터의 제어하에 관심 유전자를 암호화하는 제3 핵산;
    c. 안정적으로 형질 감염된 포유동물 세포를 TetR의 결합 파트너로 처리하는 단계;
    d. 제1, 제2 및 제3 탈억제 가능한 프로모터를 활성화시키는 단계;
    e. AAV를 생산하는 단계; 및
    f. AAV를 수확하는 단계를 포함하는 방법.
  106. 제105항에 있어서, 상기 안정적으로 형질 감염된 포유동물 세포는 충분한 양의 TetR을 생산하는 방법.
  107. 제105항 내지 제106항 중 어느 한 항에 있어서, 상기 KRAB 억제자 도메인은 TetR과 프레임에 융합된 방법.
KR1020217022728A 2018-12-21 2019-12-18 아데노 관련 바이러스 (aav) 생산자 세포주 및 관련 방법 KR20210108423A (ko)

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