KR20220010062A - 리소좀 장애를 위한 유전자 요법 - Google Patents
리소좀 장애를 위한 유전자 요법 Download PDFInfo
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Abstract
일부 측면에서, 본 개시내용은 비정상적인 리소좀 기능과 연관된 질환, 예를 들어, 파킨슨병 및 고셰병 치료를 위한 조성물 및 방법에 관한 것이다. 일부 실시양태에서, 본 개시내용은 SCNA 또는 그의 일부, TMEM106B 또는 그의 일부, 또는 상기의 임의의 조합을 표적화하는 하나 이상의 억제성 핵산을 코딩하는 트랜스진을 포함하는 발현 구축물을 제공한다. 일부 실시양태에서, 본 개시내용은 파킨슨병 방법을 필요로 하는 대상체에게 상기 발현 구축물을 투여함으로써 파킨슨병 방법을 제공한다.
Description
관련 출원
본 출원은 35 U.S.C. 119(e)하에 2017년 10월 3일 출원된 미국 가출원 일련 번호 62/567,303 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS"), 및 2017년 10월 3일 출원된 미국 가출원 일련 번호 62/567,305 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS")의 이익을 주장하고, 각 출원의 전체 내용이 본원에서 참조로 포함된다.
고셰병(Gaucher disease)은 리소좀 산 β-글루코세레브로시다제 (Gcase, "GBA")의 결핍에 기인한, 선천성 글리코스핑고리피드 대사 이상 희귀 질환이다. 환자는 간비장비대, 범혈구감소증으로 이어지는 골수 기능 부전, 폐 장애 및 섬유증, 골 결손을 비롯한, 비-CNS 증상 및 소견을 앓는다. 추가로, 상당수의 환자들은 결함성 도약 안구 운동 및 시선, 발작, 인지 결손, 발달 지연, 및 파킨슨병을 비롯한 운동 장애를 포함하는, 신경학적 증상을 앓는다.
말초 질환 및 조혈 골수 및 내장에서의 주요 임상 증상을 처리하는 여러 치료제들이 존재하며, 이는 하기 기술되는 바와 같은 효소 대체 요법, 결함성 Gcase에 결합하고, 안정성을 개선시키는 샤페론 유사 소분자 약물, 및 증상 및 소견으로 이어지는, 고셰병에서 축적되는 기질의 생산을 차단하는 기질 감소 요법을 포함한다. 그러나, 고셰병의 다른 측면 (특히, 골격 및 뇌에서 발병되는 것)은 치료에 대하여 난치성인 것으로 보인다.
(GBA1 유전자의 두 염색체 대립유전자 모두에 돌연변이를 갖는) 고셰병 환자 이외에도, GBA1의 단 하나의 대립유전자에만 돌연변이를 갖는 환자는 파킨슨병 (PD)에 걸릴 위험이 매우 높다. 보행 장애, 휴식시 떨림, 경직, 및 흔히 우울증, 수면 장애, 및 인지 저하를 포함하는, PD 증상의 중증도는 효소 활성 감소 정도와 상관관계를 갖는다. 따라서, 고셰병 환자는 가장 중증의 과정을 갖는 반면, GBA1 중 단일의 가벼운 돌연변이를 갖는 환자는 전형적으로 더욱 양성의 과정을 갖는다. 돌연변이 보유자는 또한, 실행 기능 장애, 정신병, 및 PD 유사 운동 장애를 특징으로 하는 루이소체 치매, 및 특유의 운동 및 인지 장애를 갖는 다계통 위축을 비롯한, 다른 PD 관련 장애의 위험이 높다. 이러한 장애의 거침없이 계속되는 과정을 변경하는 요법은 현재 없다.
일부 측면에서, 본 개시내용은 PD 연관 유전자 (예컨대, α-시누클레인 (α-Syn), 막횡단 단백질 106B (TMEM106B), 리보솜 단백질 s25 (RPS25), 미세소관 결합 단백질 타우 (MAPT), 또는 그의 조합)를 표적화하는 하나 이상의 억제성 RNA (예컨대, shRNA, miRNA 등)를 코딩하는 발현 구축물에 기초한다. 일부 측면에서, 본 개시내용은 Gcase (또는 그의 일부) 및 PD 연관 유전자 (예컨대, α-Syn)로부터의 하나 이상의 추가 유전자 생성물을 코딩하는 발현 구축물 (예컨대, 벡터)에 기초한다. 어느 특정 이론에 의해 제한하고자 하지 않으면서, 본원에 기술된 유전자 생성물의 조합은 대상체에서 발현되었을 때, 함께 (예컨대, 시너지적으로) 작용하여 PD의 하나 이상의 징후 및 증상을 감소시킨다.
따라서, 일부 측면에서, 본 개시내용은 SNCA (예컨대, SCNA의 일부)를 표적화하고, α-Syn의 발현 및/또는 활성을 억제시키는 억제성 RNA를 코딩하는 단리된 핵산을 제공한다. 일부 측면에서, 본 개시내용은 제1 유전자 생성물 및 제2 유전자 생성물을 코딩하는 발현 구축물을 포함하는 단리된 핵산이며, 여기서 각 유전자 생성물은 독립적으로 표 1에 기재된 유전자 생성물 또는 그의 일부로부터 선택되는 것인, 단리된 핵산을 제공한다.
따라서, 일부 측면에서, 본 개시내용은 TMEM106B (예컨대, TMEM106B의 일부)를 표적화하고, TMEM106B의 발현 및/또는 활성을 억제시키는 억제성 RNA를 코딩하는 단리된 핵산을 제공한다. 일부 측면에서, 본 개시내용은 제1 유전자 생성물 및 제2 유전자 생성물을 코딩하는 발현 구축물을 포함하는 단리된 핵산이며, 여기서 각 유전자 생성물은 독립적으로 표 1에 기재된 유전자 생성물 또는 그의 일부로부터 선택되는 것인, 단리된 핵산을 제공한다.
따라서, 일부 측면에서, 본 개시내용은 RPS25를 코딩하는 유전자 (예컨대, RPS25를 코딩하는 유전자의 일부)를 표적화하고, RPS25의 발현 및/또는 활성을 억제시키는 억제성 RNA를 코딩하는 단리된 핵산을 제공한다. 일부 측면에서, 본 개시내용은 제1 유전자 생성물 및 제2 유전자 생성물을 코딩하는 발현 구축물을 포함하는 단리된 핵산이며, 여기서 각 유전자 생성물은 독립적으로 표 1에 기재된 유전자 생성물 또는 그의 일부로부터 선택되는 것인, 단리된 핵산을 제공한다.
따라서, 일부 측면에서, 본 개시내용은 MAPT (예컨대, MAPT를 코딩하는 유전자의 일부)를 표적화하고, MAPT의 발현 및/또는 활성을 억제시키는 억제성 RNA를 코딩하는 단리된 핵산을 제공한다. 일부 측면에서, 본 개시내용은 제1 유전자 생성물 및 제2 유전자 생성물을 코딩하는 발현 구축물을 포함하는 단리된 핵산이며, 여기서 각 유전자 생성물은 독립적으로 표 1에 기재된 유전자 생성물 또는 그의 일부로부터 선택되는 것인, 단리된 핵산을 제공한다.
일부 실시양태에서, 제1 유전자 생성물 또는 제2 유전자 생성물은 Gcase 단백질, 또는 그의 일부이다. 일부 실시양태에서, 제1 유전자 생성물 또는 제2 유전자 생성물은 간섭 핵산 (예컨대, shRNA, miRNA, dsRNA 등)이다. 일부 실시양태에서, 간섭 핵산은 α-시누클레인 (α-시누클레인)의 발현을 억제시킨다. 일부 실시양태에서, 제1 유전자 생성물은 Gcase 단백질이고, 제2 유전자 생성물은 α-Syn의 발현을 억제시키는 간섭 핵산 (예컨대, shRNA, miRNA, dsRNA 등) (예컨대, SCNA를 표적화하는 간섭 핵산)이다.
일부 실시양태에서, 간섭 핵산은 TMEM106B의 발현을 억제시킨다. 일부 실시양태에서, 제1 유전자 생성물은 Gcase 단백질이고, 제2 유전자 생성물은 TMEM106B의 발현을 억제시키는 간섭 핵산 (예컨대, shRNA, miRNA, dsRNA 등) (예컨대, TMEM106B를 표적화하는 간섭 핵산)이다.
일부 실시양태에서, 간섭 핵산은 RPS25의 발현을 억제시킨다. 일부 실시양태에서, 제1 유전자 생성물은 Gcase 단백질이고, 제2 유전자 생성물은 RPS25를 코딩하는 유전자의 발현을 억제시키는 간섭 핵산 (예컨대, shRNA, miRNA, dsRNA 등) (예컨대, RPS25 코딩 서열을 표적화하는 간섭 핵산)이다.
일부 실시양태에서, 간섭 핵산은 MAPT의 발현을 억제시킨다. 일부 실시양태에서, 제1 유전자 생성물은 Gcase 단백질이고, 제2 유전자 생성물은 MAPT의 발현을 억제시키는 간섭 핵산 (예컨대, shRNA, miRNA, dsRNA 등) (예컨대, MAPT를 표적화하는 간섭 핵산)이다.
일부 실시양태에서, 발현 구축물은 하나 이상의 프로모터를 추가로 포함한다. 일부 실시양태에서, 프로모터는 닭 베타 액틴 (CBA) 프로모터, CAG 프로모터, CD68 프로모터, 또는 JeT 프로모터이다. 일부 실시양태에서, 프로모터는 RNA pol II 프로모터 또는 RNA pol III 프로모터 (예컨대, U6)이다.
일부 실시양태에서, 발현 구축물은 내부 리보솜 진입 부위 (IRES)를 추가로 포함한다. 일부 실시양태에서, IRES는 제1 유전자 생성물과 제2 유전자 생성물 사이에 위치한다.
일부 실시양태에서, 발현 구축물은 자기 절단 펩티드 코딩 서열을 추가로 포함한다. 일부 실시양태에서, 자기 절단 펩티드는 T2A 펩티드이다.
일부 실시양태에서, 발현 구축물은 2개의 아데노-연관 바이러스 (AAV) 역전된 말단 반복부 (ITR) 서열을 포함한다. 일부 실시양태에서, ITR 서열은 제1 유전자 생성물 및 제2 유전자 생성물에 플랭킹된다 (예컨대, 5' 단부에서 3' 단부 방향으로 하기와 같이 배열되어 있다: ITR-제1 유전자 생성물-제2 유전자 생성물-ITR). 일부 실시양태에서, 단리된 핵산의 ITR 서열 중 하나에는 기능성 말단 분해 부위 (trs)가 결손되어 있다. 예를 들어, 일부 실시양태에서, ITR 중 하나는 ΔITR이다.
일부 측면에서, 본 개시내용은 변형된 "D" 영역 (예컨대, 야생형 AAV2 ITR 기준으로 변형된 D 서열, 서열식별번호(SEQ ID NO:) 16)을 갖는 ITR을 포함하는 rAAV 벡터에 관한 것이다. 일부 실시양태에서, 변형된 D 영역을 갖는 ITR은 rAAV 벡터의 5' ITR이다. 일부 실시양태에서, 변형된 "D" 영역은 예를 들어, 서열식별번호 13에 기재되어 있는 바와 같은 "S" 서열을 포함한다. 일부 실시양태에서, 변형된 "D" 영역을 갖는 ITR은 rAAV 벡터의 3' ITR이다. 일부 실시양태에서, 일부 실시양태에서, 변형된 "D" 영역은 "D" 영역이 ITR의 3' 단부에 (예컨대, 벡터의 트랜스진 인서트 기준으로 ITR의 외부 또는 말단 단부 상에) 위치하는 3' ITR을 포함한다. 일부 실시양태에서, 변형된 "D" 영역은 서열식별번호 13 또는 14에 기재되어 있는 바와 같은 서열을 포함한다.
일부 실시양태에서, 단리된 핵산 (예컨대, rAAV 벡터)는 TRY 영역을 포함한다. 일부 실시양태에서, TRY 영역은 서열식별번호 16에 기재되어 있는 바와 같은 서열을 포함한다.
일부 실시양태에서, 본 개시내용에 의해 기술된 단리된 핵산은 서열식별번호 1-67에 기재된 서열을 포함하거나 또는 그로 이루어진다.
일부 측면에서, 본 개시내용은 본 개시내용에 의해 기술된 바와 같은 단리된 핵산을 포함하는 벡터를 제공한다. 일부 실시양태에서, 벡터는 플라스미드, 또는 바이러스 벡터이다. 일부 실시양태에서, 바이러스 벡터는 재조합 AAV (rAAV) 벡터또는 배큘로바이러스 벡터이다. 일부 실시양태에서, rAAV 벡터는 단일-가닥 (예컨대, 단일-가닥 DNA)이다.
일부 측면에서, 본 개시내용은 본 개시내용에 의해 기술된 바와 같은 단리된 핵산, 또는 본 개시내용에 의해 기술된 바와 같은 벡터를 포함하는 숙주 세포를 제공한다.
일부 측면에서, 본 개시내용은 본 개시내용에 의해 기술된 바와 같은 캡시드 단백질 및 단리된 핵산 또는 벡터를 포함하는 재조합 아데노-연관 바이러스 (rAAV)를 제공한다.
일부 실시양태에서, 캡시드 단백질, 예를 들어, AAV9 캡시드 단백질 또는 AAVrh.10 캡시드 단백질은 혈액-뇌 장벽을 건널 수 있다. 일부 실시양태에서, rAAV는 중추 신경계 (CNS)의 뉴런 세포 및 비-뉴런 세포를 형질도입한다.
일부 측면에서, 본 개시내용은 파킨슨병을 앓거나 또는 앓을 것으로 의심되는 대상체에게 본 개시내용에 의해 기술된 바와 같은 조성물 (예컨대, 단리된 핵산 또는 벡터 또는 rAAV를 포함하는 조성물)을 투여하는 단계를 포함하는, 파킨슨병을 앓거나 또는 앓을 것으로 의심되는 대상체를 치료하는 방법을 제공한다.
일부 실시양태에서, 투여는 대상체의 CNS에의 직접 주사를 포함한다. 일부 실시양태에서, 직접 주사는 대뇌내 주사, 실질내 주사, 경막내 주사, 대수조내 주사, 또는 그의 임의의 조합이다. 일부 실시양태에서, 대상체의 CNS에의 직접 주사는 컨벡션 강화 전달법 (CED)을 포함한다.
일부 실시양태에서, 투여는 말초 주사를 포함한다. 일부 실시양태에서, 말초 주사는 정맥내 주사이다.
도 1은 Gcase (예컨대, GBA1 또는 그의 일부) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 벡터의 한 실시양태를 도시한 개략도이다.
도 2는 SCNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 3은 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 4는 프로그래뉼린 (PGRN) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 5는 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 6은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 7은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 3' ITR의 "D" 서열은 벡터의 "외부"에 위치한다.
도 8은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 9는 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 10은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 11은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 12는 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 13은 Gcase (GBA1) 및 프로그래뉼린 (PGRN), 및 TMEM106B를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 14는 GFP 리포터 검정법 (상단) 및 α-Syn 검정법 (하단)에 의해, 시험관내에서 SCNA의 침묵화가 성공적으로 이루어졌다는 것을 나타내는 대표적인 데이터를 보여주는 것이다.
도 15는 GFP 리포터 검정법 (상단) 및 α-Syn 검정법 (하단)에 의해, 시험관내에서 TMEM106B의 침묵화가 성공적으로 이루어졌다는 것을 나타내는 대표적인 데이터를 보여주는 것이다.
도 16은 ITR의 "외부"에 (예컨대, 트랜스진 인서트 또는 발현 구축물 기준으로 ITR의 말단에 인접하게) 위치하는 "D" 영역을 포함하는 rAAV 벡터 (상단), 및 벡터의 "내부"에 (예컨대, 벡터의 트랜스진 인서트에 인접한 위치에) ITR을 갖는 야생형 rAAV 벡터를 도시한 개략도이다.
도 17은 "D" 서열이 야생형으로 (동그라미 표시) 또는 대안적으로 (예컨대, "외부에"; 사각형 표시) 배치되어 있는 ITR을 갖는 rAAV를 이용한 HEK293 세포의 형질도입에 대한 데이터를 보여주는 것이다. "외부에" 배치된 ITR을 갖는 rAAV는 야생형 ITR을 갖는 rAAV만큼 효율적으로 세포를 형질도입시킬 수 있었다.
도 18은 RPS25를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 19는 RPS25를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 20은 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 21은 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 22는 프로그래뉼린 (PGRN) 및 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 PGRN 코딩 서열 사이의 인트론 내에 위치한다.
도 23은 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 24는 프로그래뉼린 (PGRN) 및 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 PGRN 코딩 서열 사이의 인트론 내에 위치한다.
도 2는 SCNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 3은 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 4는 프로그래뉼린 (PGRN) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 5는 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 6은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 7은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 3' ITR의 "D" 서열은 벡터의 "외부"에 위치한다.
도 8은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 9는 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 10은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 11은 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 12는 Gcase (GBA1) 및 SCNA를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 13은 Gcase (GBA1) 및 프로그래뉼린 (PGRN), 및 TMEM106B를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 Gcase 코딩 서열 사이의 인트론 내에 위치한다.
도 14는 GFP 리포터 검정법 (상단) 및 α-Syn 검정법 (하단)에 의해, 시험관내에서 SCNA의 침묵화가 성공적으로 이루어졌다는 것을 나타내는 대표적인 데이터를 보여주는 것이다.
도 15는 GFP 리포터 검정법 (상단) 및 α-Syn 검정법 (하단)에 의해, 시험관내에서 TMEM106B의 침묵화가 성공적으로 이루어졌다는 것을 나타내는 대표적인 데이터를 보여주는 것이다.
도 16은 ITR의 "외부"에 (예컨대, 트랜스진 인서트 또는 발현 구축물 기준으로 ITR의 말단에 인접하게) 위치하는 "D" 영역을 포함하는 rAAV 벡터 (상단), 및 벡터의 "내부"에 (예컨대, 벡터의 트랜스진 인서트에 인접한 위치에) ITR을 갖는 야생형 rAAV 벡터를 도시한 개략도이다.
도 17은 "D" 서열이 야생형으로 (동그라미 표시) 또는 대안적으로 (예컨대, "외부에"; 사각형 표시) 배치되어 있는 ITR을 갖는 rAAV를 이용한 HEK293 세포의 형질도입에 대한 데이터를 보여주는 것이다. "외부에" 배치된 ITR을 갖는 rAAV는 야생형 ITR을 갖는 rAAV만큼 효율적으로 세포를 형질도입시킬 수 있었다.
도 18은 RPS25를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 19는 RPS25를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 20은 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 21은 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 22는 프로그래뉼린 (PGRN) 및 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 PGRN 코딩 서열 사이의 인트론 내에 위치한다.
도 23은 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다.
도 24는 프로그래뉼린 (PGRN) 및 MAPT를 표적화하는 억제성 RNA를 코딩하는 발현 구축물을 포함하는 rAAV 벡터를 포함하는 플라스미드의 한 실시양태를 도시한 개략도이다. 억제성 RNA는 프로모터 서열과 PGRN 코딩 서열 사이의 인트론 내에 위치한다.
본 개시내용은 부분적으로 대상체에서 PD 연관 유전자 생성물의 조합의 발현을 위한 조성물 및 방법에 기초한다. 유전자 생성물은 단백질, 단백질의 단편 (예컨대, 일부), PD 연관 유전자를 억제시키는 간섭 핵산 등일 수 있다. 일부 실시양태에서, 유전자 생성물은 PD 연관 유전자에 의해 코딩되는 단백질 또는 단백질 단편이다. 일부 실시양태에서, 유전자 생성물은 PD 연관 유전자를 억제시키는 간섭 핵산 (예컨대, shRNA, siRNA, miRNA, amiRNA 등)이다.
PD 연관 유전자란, PD와 유전적으로, 생화학적으로 또는 기능적으로 연관이 있는 유전자 생성물을 코딩하는 유전자를 지칭한다. 예를 들어, (단백질 Gcase를 코딩하는) GBA1 유전자 중 돌연변이를 갖는 개체는 GBA1 중에 돌연변이를 가지지 않는 것과 비교하였을 때, PD가 발생할 위험이 증가되어 있는 것으로 관찰되었다. 또 다른 예에서, PD는 α-시누클레인 (α-Syn)을 포함하는 단백질 응집체의 축적과 연관이 있고; 따라서, (α-Syn을 코딩하는) SCNA가 PD 연관 유전자이다. 일부 실시양태에서, 본원에 기술된 발현 카세트는 야생형 또는 비-돌연변이체 형태의 PD 연관 유전자 (또는 그의 코딩 서열)이다. PD 연관 유전자의 예는 표 1에 열거되어 있다.
<표 1>
PD 연관 유전자의 예
단리된 핵산 및 벡터
단리된 핵산은 DNA 또는 RNA일 수 있다. 일부 측면에서, 본 개시내용은 하나 이상의 PD 연관 유전자, 예를 들어, SCNA, TMEM106B, RPS25, 및 MAPT를 표적화하는 하나 이상의 억제성 핵산을 코딩하는 단리된 핵산 (예컨대, rAAV 벡터)을 제공한다. 일부 실시양태에서, 단리된 핵산은 단백질 코딩 서열, 예를 들어, Gcase (예컨대, GBA1) 또는 프로그래뉼린 (예컨대, PGRN)을 코딩하는 핵산 서열을 추가로 포함한다.
일반적으로, 본원에 기술된 단리된 핵산은 1, 2, 3, 4, 5, 6, 7, 8, 9, 10개, 또는 그 초과의 억제성 핵산 (예컨대, dsRNA, siRNA, shRNA, miRNA, amiRNA 등)을 코딩할 수 있다. 일부 실시양태에서, 단리된 핵산은 10개 초과의 억제성 핵산을 코딩한다. 일부 실시양태에서, 하나 이상의 억제성 핵산은 각각 상이한 유전자 또는 유전자의 일부를 표적화한다 (예컨대, 제1 miRNA는 유전자의 제1 표적 서열을 표적화하고, 제2 miRNA는 제1 표적 서열과 상이한 유전자의 제2 표적 서열을 표적화한다). 일부 실시양태에서, 하나 이상의 억제성 핵산은 각각 동일한 유전자의 동일한 표적 서열을 표적화한다 (예컨대, 단리된 핵산은 동일한 miRNA의 다중 카피를 코딩한다).
본 개시내용의 측면은 α-시누클레인 단백질 (예컨대, SCNA 유전자의 유전자 생성물)을 표적화하는 하나 이상의 간섭 핵산 (예컨대, dsRNA, siRNA, miRNA, amiRNA 등)을 코딩하는 발현 구축물을 포함하는 단리된 핵산에 관한 것이다. α-시누클레인 단백질은, 시냅스 소포체를 클러스터링함으로써 시냅스 전 말단에서 시냅스 소포체의 공급을 유지하고, 도파민의 방출을 조절하는 데 중요한 역할을 하는, 뇌 조직에서 발견되는 단백질을 지칭한다. 인간에서, SCNA 유전자는 염색체 4에 위치한다. 일부 실시양태에서, SCNA 유전자는 NCBI 참조 서열(NCBI Reference Sequence) NP_001139527.1에 의해 제시되는 펩티드를 코딩한다. 일부 실시양태에서, SCNA 유전자는 서열식별번호 1에 기재된 서열을 포함한다.
SCNA를 표적화하는 억제성 핵산은 길이가 6 내지 50개의 뉴클레오티드 길이인, 상보성 영역 (예컨대, 표적 유전자, 예컨대, SCNA에 하이브리드화하는 억제성 핵산의 영역)을 포함할 수 있다. 일부 실시양태에서, 억제성 핵산은 길이가 약 6 내지 30개, 약 8 내지 20개, 또는 약 10 내지 19개의 뉴클레오티드 길이인, SCNA와 상보성인 영역을 포함한다. 일부 실시양태에서, 억제성 핵산은 SCNA 서열의 적어도 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 또는 25개의 연속적인 뉴클레오티드와 상보성이다.
본 개시내용의 측면은 TMEM106B 단백질 (예컨대, SCNA 유전자의 유전자 생성물)을 표적화하는 하나 이상의 간섭 핵산 (예컨대, dsRNA, siRNA, miRNA, amiRNA 등)을 코딩하는 발현 구축물을 포함하는 단리된 핵산에 관한 것이다. TMEM106B 단백질은, 수상돌기 형태발생 및 리소좀 수송 조절에 관여하는 단백질인, 막횡단 단백질 106B를 지칭한다. 인간에서, TMEM106B 유전자는 염색체 7에 위치한다. 일부 실시양태에서, TMEM106B 유전자는 NCBI 참조 서열 NP_060844.2에 의해 제시되는 펩티드를 코딩한다. 일부 실시양태에서, TMEM106B 유전자는 서열식별번호 2에 기재된 서열을 포함한다.
TMEM106B를 표적화하는 억제성 핵산은 길이가 6 내지 50개의 뉴클레오티드 길이인, 상보성 영역 (예컨대, 표적 유전자, 예컨대, TMEM106B에 하이브리드화하는 억제성 핵산의 영역)을 포함할 수 있다. 일부 실시양태에서, 억제성 핵산은 길이가 약 6 내지 30개, 약 8 내지 20개, 또는 약 10 내지 19개의 뉴클레오티드 길이인, TMEM106B와 상보성인 영역을 포함한다. 일부 실시양태에서, 억제성 핵산은 TMEM106B 서열의 적어도 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 또는 25개의 연속적인 뉴클레오티드와 상보성이다.
본 개시내용의 측면은 리보솜 단백질 s25 (RPS25) (예컨대, RPS25 유전자의 유전자 생성물)을 표적화하는 하나 이상의 간섭 핵산 (예컨대, dsRNA, siRNA, miRNA, amiRNA 등)을 코딩하는 발현 구축물을 포함하는 단리된 핵산에 관한 것이다. RPS25 단백질은, 단백질 합성에 관여하는 단백질 복합체인 s40 리보솜의 서브유닛인 리보솜 단백질을 지칭한다. 인간에서, RPS25 유전자는 염색체 11에 위치한다. 일부 실시양태에서, RPS25 유전자는 NCBI 참조 서열 NP_001019.1에 의해 제시되는 펩티드를 코딩한다. 일부 실시양태에서, RPS25 유전자는 서열식별번호 36에 기재된 서열을 포함한다.
RPS25를 표적화하는 억제성 핵산은 길이가 6 내지 50개의 뉴클레오티드 길이인, 상보성 영역 (예컨대, 표적 유전자, 예컨대, RPS25에 하이브리드화하는 억제성 핵산의 영역)을 포함할 수 있다. 일부 실시양태에서, 억제성 핵산은 길이가 약 6 내지 30개, 약 8 내지 20개, 또는 약 10 내지 19개의 뉴클레오티드 길이인, RPS25와 상보성인 영역을 포함한다. 일부 실시양태에서, 억제성 핵산은 RPS25 서열의 적어도 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 또는 25개의 연속적인 뉴클레오티드와 상보성이다.
본 개시내용의 측면은 미세소관 결합 단백질 타우, MAPT (예컨대, MAPT 유전자의 유전자 생성물)을 표적화하는 하나 이상의 간섭 핵산 (예컨대, dsRNA, siRNA, miRNA, amiRNA 등)을 코딩하는 발현 구축물을 포함하는 단리된 핵산에 관한 것이다. MAPT 단백질은 미세소관 안정화에 관여하는 단백질인 미세소관 결합 단백질을 지칭한다. 인간에서, MAPT 유전자는 염색체 17에 위치한다. 일부 실시양태에서, MAPT 유전자는 NCBI 참조 서열 NP_005901.2에 의해 제시되는 펩티드를 코딩한다. 일부 실시양태에서, MAPT 유전자는 서열식별번호 37에 기재된 서열을 포함한다.
MAPT를 표적화하는 억제성 핵산은 길이가 6 내지 50개의 뉴클레오티드 길이인, 상보성 영역 (예컨대, 표적 유전자, 예컨대, MAPT에 하이브리드화하는 억제성 핵산의 영역)을 포함할 수 있다. 일부 실시양태에서, 억제성 핵산은 길이가 약 6 내지 30개, 약 8 내지 20개, 또는 약 10 내지 19개의 뉴클레오티드 길이인, MAPT와 상보성인 영역을 포함한다. 일부 실시양태에서, 억제성 핵산은 MAPT 서열의 적어도 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 또는 25개의 연속적인 뉴클레오티드와 상보성이다.
일부 측면에서, 본 개시내용은 제1 유전자 생성물 및 제2 유전자 생성물을 코딩하는 발현 구축물을 포함하는 단리된 핵산이며, 여기서 각 유전자 생성물은 독립적으로 표 1에 기재된 유전자 생성물 또는 그의 일부로부터 선택되는 것인, 단리된 핵산을 제공한다.
일부 실시양태에서, 유전자 생성물은 자연적으로 발생된 유전자의 코딩 부분 (예컨대, cDNA)에 의해 코딩된다. 일부 실시양태에서, 제1 유전자 생성물은 GBA1 유전자에 의해 코딩된 단백질 (또는 그의 단편)이다. 일부 실시양태에서, 유전자 생성물은 PD 연관 유전자 (예컨대, SCNA)를 표적화하는 (예컨대, 그에 하이브리드화하거나, 또는 그와 상보성인 영역을 포함하는) 억제성 핵산이다. 통상의 기술자는 제1 유전자 생성물 (예컨대, Gcase) 및 제2 유전자 생성물 (예컨대, SCNA를 표적화하는 억제성 RNA)의 발현 순서가 일반적으로 역전될 수 있다는 것 (예컨대, 억제성 RNA가 제1 유전자 생성물이고, Gcase가 제2 유전자 생성물이다)을 이해한다. 일부 실시양태에서, 유전자 생성물은 표 1에 열거된 유전자의 단편 (또는 일부)이다. 단백질 단편은 표 1에 열거된 유전자에 의해 코딩된 단백질의 약 50%, 약 60%, 약 70%, 약 80%, 약 90% 또는 약 99%를 포함할 수 있다. 일부 실시양태에서, 단백질 단편은 표 1에 열거된 유전자에 의해 코딩된 단백질의 50% 내지 99.9% (예컨대, 50% 내지 99.9% 사이의 임의의 값)를 포함한다. 일부 실시양태에서, 유전자 생성물 (예컨대, 억제성 RNA)은 표적 유전자의 일부에 하이브리드화한다 (예컨대, 표적 유전자, 예를 들어, SCNA의 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21개 또는 그 초과의 연속적인 뉴클레오티드에 상보성이다).
일부 실시양태에서, 발현 구축물은 모노시스트론성이다 (예컨대, 발현 구축물은 제1 유전자 생성물 및 제2 유전자 생성물을 포함하는 단일 융합 단백질을 코딩한다). 일부 실시양태에서, 발현 구축물은 폴리시스트론성이다 (예컨대, 발현 구축물은 2개의 전혀 다른 유전자 생성물, 예를 들어, 2개의 상이한 단백질 또는 단백질 단편을 코딩한다).
폴리시스트론성 발현 벡터는 하나 이상의 (예컨대, 1, 2, 3, 4, 5개 또는 그 초과의) 프로모터를 포함할 수 있다. 임의의 적합한 프로모터, 예를 들어, 구성적 프로모터, 유도성 프로모터, 내인성 프로모터, 조직 특이적 프로모터 (예컨대, CNS 특이적 프로모터) 등이 사용될 수 있다. 일부 실시양태에서, 프로모터는 닭 베타-액틴 프로모터 (CBA 프로모터), CAG 프로모터 (예를 들어, 문헌 [Alexopoulou et al. (2008) BMC Cell Biol. 9:2; doi: 10.1186/1471-2121-9-2]에 의해 기술된 것과 같은 것), CD68 프로모터, 또는 JeT 프로모터 (예를 들어, 문헌 [Tornøe et al. (2002) Gene 297(1-2):21-32]에 의해 기술된 것과 같은 것)이다. 일부 실시양태에서, 프로모터는 제1 유전자 생성물, 제2 유전자 생성물, 또는 제1 유전자 생성물 및 제2 유전자 생성물을 코딩하는 핵산 서열에 작동가능하게 연결된다. 일부 실시양태에서, 발현 카세트는 전사 인자 결합 서열, 인트론 스플라이스 부위, 폴리(A) 부가 부위, 인핸서 서열, 리프레서 결합 부위, 또는 상기의 임의의 조합을 포함하나, 이에 제한되지 않는, 하나 이상의 추가의 조절 서열을 포함한다.
일부 실시양태에서, 제1 유전자 생성물을 코딩하는 핵산 서열 및 제2 유전자 생성물을 코딩하는 핵산 서열은 내부 리보솜 진입 부위 (IRES)를 코딩하는 핵산 서열에 의해 이격된다. IRES 부위의 예는 예를 들어, 문헌 [Mokrejs et al. (2006) Nucleic Acids Res. 34(Database issue):D125-30]에 기술되어 있다. 일부 실시양태에서, 제1 유전자 생성물을 코딩하는 핵산 서열 및 제2 유전자 생성물을 코딩하는 핵산 서열은 자기 절단 펩티드를 코딩하는 핵산 서열에 의해 이격된다. 자기 절단 펩티드의 예는 T2A, P2A, E2A, F2A, BmCPV 2A, 및 BmIFV 2A, 및 문헌 [Liu et al. (2017) Sci Rep. 7: 2193]에 의해 기술된 것을 포함하나, 이에 제한되지 않는다. 일부 실시양태에서, 자기 절단 펩티드는 T2A 펩티드이다.
병리학상, 장애, 예컨대, PD 및 고셰병은 대개는 α-시누클레인 (α-Syn) 단백질로 구성된 단백질 응집체의 축적과 연관이 있다. 따라서, 일부 실시양태에서, 본원에 기술된 단리된 핵산은 α-Syn 단백질의 발현을 감소시키거나, 또는 방해하는 억제성 핵산을 포함한다. 억제성 핵산을 코딩하는 서열은 발현 벡터의 비번역 영역 (예컨대, 인트론, 5'UTR, 3'UTR 등)에 배치될 수 있다.
일부 실시양태에서, 억제성 핵산은 발현 구축물의 인트론에, 예를 들어, 제1 유전자 생성물을 코딩하는 서열의 상류쪽 인트론에 위치한다. 억제성 핵산은 이중 가닥 RNA (dsRNA), siRNA, 마이크로RNA (miRNA), 인공 miRNA (amiRNA), 또는 RNA 압타머일 수 있다. 일반적으로, 억제성 핵산은 표적 RNA (예컨대, mRNA)의 약 6개 내지 약 30개의 (예컨대, 6 내지 30 사이의 임의의 정수 (6 및 30 포함)) 연속적인 뉴클레오티드에 결합한다 (예컨대, 그와 하이브리드화한다). 일부 실시양태에서, 억제성 핵산 분자는 miRNA 또는 amiRNA, 예를 들어, SNCA (α-Syn 단백질을 코딩하는 유전자)를 표적화하는 miRNA이다. 일부 실시양태에서, miRNA는 하이브리드화 대상인 SNCA mRNA의 영역과의 미스매치는 포함하지 않는다 (예컨대, miRNA는 "완벽한 것이다"). 일부 실시양태에서, 억제성 핵산은 shRNA (예컨대, SNCA를 표적화하는 shRNA)이다.
일부 실시양태에서, 억제성 핵산은 인공 마이크로RNA (amiRNA)이다. 마이크로RNA (miRNA)는 전형적으로 식물 및 동물에서 발견되는 소형, 비-코딩 RNA를 지칭하고, 유전자 발현의 전사 및 번역 후 조절에서 작용한다. MiRNA는 RNA 폴리머라제에 의해 전사되어 프리-miRNA로 지칭되는 헤어핀-루프 구조를 형성하고, 이는 이어서, 효소 (예컨대, 드로샤(Drosha), 파샤(Pasha), 스플라이소솜 등)에 의해 프리-miRNA 헤어핀 구조로 프로세싱되고, 이는 이어서, 다이서(Dicer)에 의해 프로세싱되어 miRNA/miRNA* 이중체 (여기서 *는 miRNA 이중체의 패신저 가닥을 나타낸다)를 형성하고, 이어서, 상기 중 한 가닥은 RNA-유도 침묵화 복합체 (RISC) 내로 도입된다. 일부 실시양태에서, 본원에 기술된 억제성 RNA는 SCNA 또는 TMEM106B를 표적화하는 miRNA이다.
일부 실시양태에서, SCNA를 표적화하는 억제성 핵산은 miRNA/miRNA* 이중체를 포함한다. 일부 실시양태에서, miRNA/miRNA* 이중체의 miRNA 가닥은 서열식별번호 3-8 중 어느 하나에 기재된 서열을 포함하거나 또는 그로 이루어진다. 일부 실시양태에서, miRNA/miRNA* 이중체의 miRNA* 가닥은 서열식별번호 3-8 중 어느 하나에 기재된 서열을 포함하거나 또는 그로 이루어진다.
일부 실시양태에서, TMEM106B를 표적화하는 억제성 핵산은 miRNA/miRNA* 이중체를 포함한다. 일부 실시양태에서, miRNA/miRNA* 이중체의 miRNA 가닥은 서열식별번호 9 또는 10에 기재된 서열을 포함하거나 또는 그로 이루어진다. 일부 실시양태에서, miRNA/miRNA* 이중체의 miRNA* 가닥은 서열식별번호 9 또는 10에 기재된 서열을 포함하거나 또는 그로 이루어진다.
인공 마이크로RNA (amiRNA)는 천연 miRNA를 변형하여 프리-mRNA의 천연 표적화 영역을 관심 표적화 영역으로 대체함으로써 유도된다. 예를 들어, 자연적으로 발현된 miRNA는 스캐폴드 또는 백본 (예컨대, 프리-miRNA 스캐폴드)으로서 사용될 수 있고, 스템 서열은 관심 유전자를 표적화하는 miRNA의 것으로 대체된다. 인공 전구체 마이크로RNA (프리-amiRNA)는 보통 하나의 단일의 안정적인 소형 RNA가 우선적으로 생성되도록 프로세싱된다. 일부 실시양태에서, 본원에 기술된 scAAV 벡터 및 scAAV는 amiRNA를 코딩하는 핵산을 포함한다. 일부 실시양태에서, amiRNA의 프리-miRNA 스캐폴드는 프리-MIR-21, 프리-MIR-22, 프리-MIR-26a, 프리-MIR-30a, 프리-MIR-33, 프리-MIR-122, 프리-MIR-375, 프리-MIR-199, 프리-MIR-99, 프리-MIR-194, 프리-MIR-155, 및 프리-MIR-451으로 이루어진 군으로부터 선택되는 프리-miRNA로부터 유도된 것이다. 일부 실시양태에서, amiRNA는 예를 들어, 문헌 [Fowler et al. Nucleic Acids Res. 2016 Mar 18; 44(5): e48]에 기술된 바와 같이, SCNA 또는 TMEM106B를 표적화하는 핵산 서열 및 eSIBR amiRNA 스캐폴드를 포함한다.
일부 실시양태에서, SCNA를 표적화하는 amiRNA는 서열식별번호 17-22 중 어느 하나에 기재된 서열을 포함하거나 또는 그로 이루어진다. 일부 실시양태에서, TMEM106B를 표적화하는 amiRNA는 서열식별번호 11 또는 12에 기재된 서열을 포함하거나 또는 그로 이루어진다. 일부 실시양태에서, RPS25를 표적화하는 amiRNA는 서열식별번호 38 내지 45에 기재된 서열을 포함하거나 또는 그로 이루어진다. 일부 실시양태에서, MAPT를 표적화하는 amiRNA는 서열식별번호 46 내지 61에 기재된 서열을 포함하거나 또는 그로 이루어진다.
본원에 기술된 단리된 핵산은 그 자체 단독으로, 또는 벡터의 일부로서 존재할 수 있다. 일반적으로, 벡터는 플라스미드, 코스미드, 파지미드, 박테리아 인공 염색체 (BAC), 또는 바이러스 벡터 (예컨대, 아데노바이러스 벡터, 아데노-연관 바이러스 (AAV) 벡터, 레트로바이러스 벡터, 배큘로바이러스 벡터 등)일 수 있다. 일부 실시양태에서, 벡터는 플라스미드 (예컨대, 본원에 기술된 바와 같은 단리된 핵산을 포함하는 플라스미드)이다. 일부 실시양태에서, 벡터는 재조합 AAV (rAAV) 벡터이다. 일부 실시양태에서, rAAV 벡터는 단일-가닥 (예컨대, 단일-가닥 DNA)이다. 일부 실시양태에서, 벡터는 배큘로바이러스 벡터 (예컨대, 오토그라파 칼리포르니카 핵 다각체병 (AcNPV) 벡터)이다.
전형적으로, rAAV 벡터 (예컨대, rAAV 게놈)는 두 AAV 역전된 말단 반복부 (ITR) 서열에 의해 플랭킹된 트랜스진 (예컨대, 하기 각각의 것: 프로모터, 인트론, 인핸서 서열, 단백질 코딩 서열, 억제성 RNA 코딩 서열, 폴리A 테일 서열 등 중 하나 이상의 것을 포함하는 발현 구축물)을 포함한다. 일부 실시양태에서, rAAV 벡터의 트랜스진은 본 개시내용에 의해 기술된 바와 같은 단리된 핵산을 포함한다. 일부 실시양태에서, rAAV 벡터의 두 ITR 서열은 각각 전장의 ITR (예컨대, 길이 대략 145 bp, 및 기능성 Rep 결합 부위 (RBS) 및 말단 분해 부위 (trs)를 함유하는 것)이다. 일부 실시양태에서, rAAV 벡터의 ITR들 중 하나는 말단절단된 것이다 (예컨대, 단축된 것이거나, 또는 전장의 것이 아니다). 일부 실시양태에서, 말단절단된 ITR에는 기능성 말단 분해 부위 (trs)가 결여되어 있고, 자기 상보성 AAV 벡터 (scAAV 벡터) 제조에 사용된다. 일부 실시양태에서, 말단절단된 ITR은 예를 들어, 문헌 [McCarty et al. (2003) Gene Ther. 10(26):2112-8]에 기술된 바와 같이, ΔITR이다.
본 개시내용의 측면은 야생형 AAV ITR 기준으로, 예를 들어, 야생형 AAV2 ITR (예컨대, 서열식별번호 16) 기준으로 하나 이상의 변형 (예컨대, 핵산 부가, 결실, 치환 등)을 갖는 ITR을 포함하는 단리된 핵산 (예컨대, rAAV 벡터)에 관한 것이다. 야생형 AAV2 ITR의 구조는 도 16에 제시되어 있다. 일반적으로, 야생형 ITR은, 자기 어닐링하여, (각각 B/B' 및 C/C'로 지칭되는 서열에 의해 형성된) 2개의 크로스 아암, (서열 A/A'에 의해 형성된) 더욱 긴 스템 영역, 및 "D" 영역으로 지칭되는 단일-가닥 말단 영역으로 이루어진 회문 이중 가닥 T 형상의 헤어핀 구조를 형성하는 125개의 뉴클레오티드 영역을 포함한다 (도 16). 일반적으로, ITR의 "D" 영역은 A/A' 서열에 의해 형성된 스템 영역과 rAAV 벡터의 트랜스진을 함유하는 인서트 사이에 위치한다 (예컨대, ITR의 말단 기준으로 ITR의 "내부"에 또는 rAAV 벡터의 트랜스진 인서트 또는 발현 구축물에 인접하게 위치한다). 일부 실시양태에서, "D" 영역은 서열식별번호 14에 기재된 서열을 포함한다. "D" 영역은 예를 들어, 문헌 [Ling et al. (2015) J Mol Genet Med 9(3)]에 개시되어 있는 바와 같이, 캡시드 단백질에 의한 rAAV 벡터의 캡시드화에서 중요한 역할을 하는 것으로 관찰되었다.
본 개시내용은 부분적으로 ITR의 "외부"에 (예컨대, 트랜스진 인서트 또는 발현 구축물 기준으로 ITR의 말단에 인접하게) 위치하는 "D" 영역을 포함하는 rAAV 벡터가 비변형된 (예컨대, 야생형) ITR로 ITR을 갖는 rAAV 벡터보다 AAV 캡시드 단백질에 의해 효율적으로 캡시드화된다는 놀라운 발견에 기초한다. 일부 실시양태에서, 변형된 "D" 서열 (예컨대, "외부 위치에 있는 "D" 서열")을 갖는 rAAV 벡터가 야생형 ITR 서열을 갖는 rAAV 벡터 기준으로 감소된 독성을 갖는다.
일부 실시양태에서, 변형된 "D" 서열은 야생형 "D" 서열 (예컨대, 서열식별번호 14) 기준으로 적어도 하나의 뉴클레오티드를 포함한다. 변형된 "D" 서열은 야생형 "D" 서열 (예컨대, 서열식별번호 14) 기준으로 적어도 1, 2, 3, 4, 5, 6, 7, 8, 9, 10개, 또는 10개 초과의 뉴클레오티드 치환을 가질 수 있다. 일부 실시양태에서, 변형된 "D" 서열은 야생형 "D" 서열 (예컨대, 서열식별번호 13) 기준으로 적어도 10, 11, 12, 13, 14, 15, 16, 17, 18, 또는 19개의 핵산 치환을 포함한다. 일부 실시양태에서, 변형된 "D" 서열은 야생형 "D" 서열 (예컨대, 서열식별번호 14)과 약 10% 내지 약 99% (예컨대, 10%, 15%, 20%, 25%, 30%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 또는 99%) 동일하다. 일부 실시양태에서, 변형된 "D" 서열은 문헌 [Wang et al. (1995) J Mol Biol 250(5):573-80]에 기술된 바와 같이 "S" 서열로도 지칭되는, 서열식별번호 13에 기재된 서열을 포함한다.
본 개시내용에 의해 기술된 바와 같은 단리된 핵산 또는 rAAV 벡터는 예를 들어, 서열식별번호 15에 기재된 바와 같은, 또는 문헌 [Francois, et al. 2005. The Cellular TATA Binding Protein Is Required for Rep-Dependent Replication of a Minimal Adeno-Associated Virus Type 2 p5 Element. J Virol]에 기술된 바와 같은 "TRY" 서열을 추가로 포함할 수 있다. 일부 실시양태에서, TRY 서열은 ITR (예컨대, 5' ITR)과 단리된 핵산 또는 rAAV 벡터의 발현 구축물 (예컨대, 트랜스진 코딩 인서트) 사이에 위치한다.
일부 측면에서, 본 개시내용은 본 개시내용에 의해 기술된 바와 같은 단리된 핵산 또는 rAAV 벡터를 포함하는 배큘로바이러스 벡터에 관한 것이다. 일부 실시양태에서, 배큘로바이러스 벡터는 예를 들어, 문헌 [Urabe et al. (2002) Hum Gene Ther 13(16):1935-43] 및 [Smith et al. (2009) Mol Ther 17(11):1888-1896]에 의해 기술된 바와 같은, 오토그라파 칼리포르니카 핵 다각체병 (AcNPV) 벡터이다.
일부 측면에서, 본 개시내용은 본원에 기술된 바와 같은 단리된 핵산 또는 벡터를 포함하는 숙주 세포를 제공한다. 숙주 세포는 원핵 세포 또는 진핵 세포일 수 있다. 예를 들어, 숙주 세포는 포유동물 세포, 박테리아 세포, 효모 세포, 곤충 세포 등일 수 있다. 일부 실시양태에서, 숙주 세포는 포유동물 세포, 예를 들어, HEK293T 세포이다. 일부 실시양태에서, 숙주 세포는 박테리아 세포, 예를 들어, E. 콜라이(E. coli) 세포이다.
rAAV
일부 측면에서, 본 개시내용은 본원에 기술된 바와 같은 핵산을 코딩하는 트랜스진을 포함하는 재조합 AAV (rAAV) (예컨대, 본원에 기술된 바와 같은 rAAV 벡터)에 관한 것이다. "rAAV"라는 용어는 일반적으로 하나 이상의 AAV 캡시드 단백질에 의해 캡시드화된 rAAV 벡터를 포함하는 바이러스 입자를 지칭한다. 본 개시내용에 의해 기술된 rAAV는 AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, 및 AAV10으로부터 선택되는 혈청형을 갖는 캡시드 단백질을 포함할 수 있다. 일부 실시양태에서, rAAV는 비-인간 숙주로부터의 캡시드 단백질, 예를 들어, 레수스 AAV 캡시드 단백질, 예컨대, AAVrh.10, AAVrh.39 등을 포함한다. 일부 실시양태에서, 본 개시내용에 의해 기술된 rAAV는 야생형 캡시드 단백질의 변이체인 캡시드 단백질, 예컨대, 유래 기점이 되는 야생형 AAV 캡시드 단백질 기준으로 적어도 1, 2, 3, 4, 5, 6, 7, 8, 9, 10개, 또는 10개 초과의 (예컨대¸ 15, 20 25, 50, 100개 등) 아미노산 치환 (예컨대, 돌연변이)을 포함하는 캡시드 단백질 변이체를 포함한다.
일부 실시양태에서, 본 개시내용에 의해 기술된 rAAV는 특히 CSF 공간 내로, 또는 뇌 실질 내로 직접 도입되었을 때, CNS를 통해 쉽게 확산된다. 따라서, 일부 실시양태에서, 본 개시내용에 의해 기술된 rAAV는 혈액-뇌 장벽 (BBB)을 건널 수 있는 캡시드 단백질을 포함한다. 예를 들어, 일부 실시양태에서, rAAV는 AAV9 또는 AAVrh.10 혈청형을 갖는 캡시드 단백질 포함한다. rAAV 제조는 예를 들어, 문헌 [Samulski et al. (1989) J Virol. 63(9):3822-8] 및 [Wright (2009) Hum Gene Ther. 20(7): 698-706]에 의해 기술되어 있다.
일부 실시양태에서, 본 개시내용에 의해 기술된 바와 같은 rAAV (예컨대, AAV 캡시드 단백질에 의해 캡시드화되어 rAAV 캡시드 입자를 형성하는 재조합 rAAV 게놈을 포함하는 것)는 배큘로바이러스 벡터 발현 시스템 (BEVS)에서 제조된다. BEVS를 이용하여 rAAV를 제조하는 것은 예를 들어, 문헌 [Urabe et al. (2002) Hum Gene Ther 13(16):1935-43], [Smith et al. (2009) Mol Ther 17(11):1888-1896], 미국 특허 번호 8,945,918, 미국 특허 번호 9,879,282, 및 국제 PCT 공개 WO 2017/184879에 의해 기술되어 있다. 그러나, rAAV는 임의의 적합한 방법 (예컨대, 재조합 rep 및 cap 유전자를 이용하는 방법)을 이용하여 제조될 수 있다.
제약 조성물
일부 측면에서, 본 개시내용은 본원에 기술된 바와 같은 단리된 핵산 또는 rAAV 및 제약상 허용되는 담체를 포함하는 제약 조성물을 제공한다. 본원에서 사용되는 바, "제약상 허용되는"이라는 용어는 물질, 예컨대, 담체 또는 희석제가 화합물의 생물학적 활성 또는 특성을 폐기하지 않고, 비교적 비독성이라는 것, 예컨대, 물질이 비바람직한 생물학적 효과를 유발하지 않거나, 또는 그와 함께 함유되어 있는 조성물의 성분 중 어느 것과도 유해한 방식으로 상호작용하지 않으면서, 개체에게 투여될 수 있다는 것을 지칭한다.
본원에서 사용되는 바, "제약상 허용되는 담체"라는 용어는 본 발명 내에서 유용한 화합물이 그의 의도된 기능을 수행할 수 있도록 상기 화합물을 환자 내에 또는 환자에게 운반 또는 수송하는 데 관여하는, 제약상 허용되는 물질, 조성물 또는 담체, 예컨대, 액체 또는 고체 충전제, 안정제, 분산화제, 현탁화제, 희석제, 부형제, 증점제, 용매 또는 캡슐화 물질을 의미한다. 본 발명의 실시에서 사용되는 제약 조성물에 포함될 수 있는 추가 성분은 관련 기술분야에 공지되어 있고, 예를 들어, 문헌 [Remington's Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985, Easton, PA)] (상기 문헌은 본원에서 참조로 포함된다)에 기술되어 있다.
본원에서 제공된 조성물 (예컨대, 제약 조성물)은 장관 (예컨대, 경구적), 비경구적, 정맥내, 근육내, 동맥내, 골수내, 경막내, 피하, 뇌실내, 경피, 피부간(interdermal), 직장, 질내, 복강내, 국소 (분제, 연고, 크림제, 및/또는 점적제에 의한 경우), 점막, 비강, 협착, 설하를 비롯한, 임의의 경로에 의해; 기관내 주입, 기관지 주입, 및/또는 흡입에 의해; 및/또는 경구용 스프레이, 비강용 스프레이, 및/또는 에어로졸로서 투여될 수 있다. 경구 투여, 정맥내 투여 (예컨대, 전신 정맥내 주사), 혈액 및/또는 림프 공급을 통한 국부 투여, 및/또는 환부로의 직접 투여가 구체적으로 고려되는 경로이다. 일반적으로, 가장 적절한 투여 경로는 작용제의 성질 (예컨대, 위장관 환경에서의 그의 안정성), 및/또는 대상체의 상태 (예컨대, 대상체가 경구 투여를 허용할 수 있는지 여부)를 비롯한, 다양한 인자에 의존할 것이다. 특정 실시양태에서, 본원에 기술된 화합물 또는 제약 조성물은 대상체의 안구로의 국소 투여에 적합하다.
방법
본 개시내용은 부분적으로 함께 (예컨대, 시너지적으로) 작용하여 파킨슨병을 치료하는, 대상체에서의 PD 연관 유전자 생성물의 조합의 발현을 위한 조성물에 기초한다. 본원에서 사용되는 바, "치료하다" 또는 "치료하는"이라는 것은 (a) 파킨슨병의 발병을 예방하거나, 또는 지연시키고/거나; (b) 파킨슨병의 중증도를 감소시키고/거나; (c) 파킨슨병의 특징적인 증상의 발생을 감소시키거나, 또는 예방하고/거나; (d) 파킨슨병의 특징적인 증상의 악화를 예방하는 것을 지칭한다. 파킨슨병의 증상으로는 예를 들어, 운동 기능장애 (예컨대, 떨림, 경직, 몸동작이 느려지는 서동, 보행 곤란), 인지 기능장애 (예컨대, 치매, 우울증, 불안), 감정 및 행동 기능장애를 포함한다.
따라서, 일부 측면에서, 본 개시내용은 파킨슨병을 앓거나 또는 앓을 것으로 의심되는 대상체에게 본 개시내용에 의해 기술된 바와 같은 조성물 (예컨대, 단리된 핵산 또는 벡터 또는 rAAV를 포함하는 조성물)을 투여하는 단계를 포함하는, 파킨슨병을 앓거나 또는 앓을 것으로 의심되는 대상체를 치료하는 방법을 제공한다.
일부 실시양태에서, 조성물은 대상체의 CNS로 직접, 예를 들어, 대상체의 뇌 및/또는 척수 내로의 직접 주사에 의해 투여된다. CNS 직접 투여 방식의 예로는 대뇌내 주사, 뇌실내 주사, 수조내 주사, 실질내 주사, 경막내 주사, 및 상기의 임의의 조합을 포함하나, 이에 제한되지 않는다. 일부 실시양태에서, 대상체의 CNS 내로 직접 주사하면, 그 결과로 트랜스진은 대상체의 중뇌, 선조체 및/또는 대뇌 피질에서 발현된다 (예컨대, 제1 유전자 생성물, 제2 유전자 생성물, 및 적용가능할 경우, 제3 유전자 생성물은 발현된다). 일부 실시양태에서, CNS 내로 직접 주사하면, 그 결과로 트랜스진은 대상체의 척수 및/또는 CSF에서 발현된다 (예컨대, 제1 유전자 생성물, 제2 유전자 생성물, 및 적용가능할 경우, 제3 유전자 생성물은 발현된다).
일부 실시양태에서, 대상체의 CNS로의 직접 주사는 컨벡션 강화 전달법 (CED)을 포함한다. 컨벡션 강화 전달법은 뇌를 외과적으로 노출시키고, 뇌의 표적 부위 내로 직접 소경 카테터를 배치한 후, 이어서, 치료제 (예컨대, 본원에 기술된 바와 같은 조성물 또는 rAAV)를 대상체의 뇌로 직접 주입하는 것을 포함하는 치료 전략법이다. CED는 예를 들어, 문헌 [Debinski et al. (2009) Expert Rev Neurother. 9(10):1519-27]에 의해 기술되어 있다.
일부 실시양태에서, 조성물은 대상체에게 예를 들어, 말초 주사에 의해 말초적으로 투여된다. 말초 주사의 예로는 피하 주사, 정맥내 주사, 동맥내 주사, 복강내 주사, 또는 상기의 임의의 조합을 포함한다. 일부 실시양태에서, 말초 주사는 동맥내 주사, 예를 들어, 대상체의 경동맥 내로의 주사이다.
일부 실시양태에서, 본 개시내용에 의해 기술된 바와 같은 조성물 (예컨대, 단리된 핵산 또는 벡터 또는 rAAV를 포함하는 조성물)은 말초적으로 및 대상체의 CNS로 직접, 상기 두 방식 모두에 의해 투여된다. 예를 들어, 일부 실시양태에서, 대상체는 동맥내 주사에 의해 (예컨대, 경동맥 내로의 주사에 의해), 및 실질내 주사에 의해 (예컨대, CED에 의한 실질내 주사에 의해) 조성물을 투여받는다. 일부 실시양태에서, CNS로의 직접 주사 및 말초 주사는 동시에 이루어진다 (예컨대, 같은 시간에 수행된다). 일부 실시양태에서, 직접 주사는 말초 주사 이전에 (예컨대, 말초 주사 전 1분 내지 1주 사이에, 또는 그를 초과하는 시간에) 이루어진다. 일부 실시양태에서, 직접 주사는 말초 주사 이후에 (예컨대, 말초 주사 후 1분 내지 1주 사이에, 또는 그를 초과하는 시간에) 이루어진다.
대상체에게 투여되는 본 개시내용에 의해 기술된 바와 같은 조성물 (예컨대, 단리된 핵산 또는 벡터 또는 rAAV를 포함하는 조성물)의 양은 투여 방법에 의존하여 달라질 것이다. 예를 들어, 일부 실시양태에서, 본원에 기술된 바와 같은 rAAV는 약 109 게놈 카피 (GC)/kg 내지 약 1014 GC/kg (예컨대, 약 109 GC/kg, 약 1010 GC/kg, 약 1011 GC/kg, 약 1012 GC/kg, 약 1012 GC/kg, 또는 약 1014 GC/kg)의 역가로 대상체에게 투여된다. 일부 실시양태에서, 대상체는 CSF 공간으로의 주사에 의해, 또는 실질내 주사에 의해 고역가로 (예컨대, >1012 게놈 카피 GC/kg (rAAV)) 투여받는다.
본 개시내용에 의해 기술된 바와 같은 조성물 (예컨대, 단리된 핵산 또는 벡터 또는 rAAV를 포함하는 조성물)은 1회 또는 다회에 걸쳐 (예컨대, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20회 또는 그 초과) 대상체에게 투여될 수 있다. 일부 실시양태에서, 조성물은 대상체에게 연속하여 (예컨대, 만성적으로), 예를 들어, 주입 펌프를 통해 투여된다.
실시예
실시예 1: rAAV 벡터
삼중-플라스미드 형질감염을 위해 세포, 예컨대, HEK293 세포를 사용하여 AAV 벡터를 생성한다. ITR 서열은 각 관심 트랜스진에 대한 프로모터/인핸서 요소, 3' 폴리A 신호, 및 번역 후 신호, 예컨대, WPRE 요소를 포함하는 발현 구축물에 플랭킹된다. 예를 들어, 2개의 별개의 발현 카세트를 이용하는 발현에 의해 예컨대, GBA1 및 하나 이상의 억제성 핵산 (예컨대, SCNA를 표적화하는 억제성 핵산)과 같은 다중 유전자 생성물이 동시에 발현될 수 있다. 발현 유전자 상류쪽의 효율적으로 스플라이싱된 짧은 인트론 서열의 존재가 발현 수준을 개선시킬 수 있다. shRNA 및 다른 조절 RNA가 잠재적으로 상기 서열 내에 포함될 수 있다. 본 개시내용에 의해 기술된 발현 구축물의 예는 도 1-13 및 18-24, 및 하기 표 2에 제시되어 있다.
<표 2>
실시예 2: GBA 결핍 세포로의 바이러스 형질도입에 관한 세포 기반 검정법
예를 들어, GD 환자 단핵구, 또는 hES 세포로부터의 섬유모세포, 또는 환자 유래의 유도 만능 줄기 세포 (iPSC)로서 GBA1 결핍 세포를 수득한다. 이들 세포는 기질, 예컨대, 글루코실세라미드 및 글루코실스핑고신 (GluCer 및 GluSph)을 축적한다. 야생형 또는 돌연변이체 배양 세포주를 Gcase 억제제, 예컨대, CBE로 처리하는 것 또한 GBA 결핍 세포를 수득하는 데 사용된다.
상기 세포 모델을 이용하여, 해당 단백질에 대한 항체 또는 포스포-αSyn을 이용한 후, 형광 현미경법을 이용하여 영상화함으로써 단백질 응집체, 예컨대, α-시누클레인의 축적에 의해 리소좀 결함을 정량화한다. 단백질 마커, 예컨대, LAMP1, LAMP2, LIMP1, LIMP2에 대한 ICC에 의해, 또는 염료, 예컨대, 리소트래커(Lysotracker)를 사용하여, 또는 형광성 덱스트란 또는 다른 마커의 세포내이입 구획을 통한 흡수에 의해 리소좀 이상에 대한 영상화 또한 수행한다. 리소좀과의 결함성 융합에 기인하는 자가포식 마커 축적에 대한, 예컨대 LC3에 대한 영상화 또한 수행될 수 있다. 웨스턴 블롯 및/또는 ELISA는 상기 마커의 비정상적인 축적을 정량화하는 데 사용된다. 또한, 당지질 기질 및 GBA1의 생성물의 축적은 표준 접근법을 이용하여 측정된다.
치료 종점 (예컨대, PD 연관 병상의 감소)은 활성 및 기능을 확인하고, 정량화하기 위해 AAV 벡터의 형질도임의 발현과 관련하여 측정된다. Gcase는 또한 단백질 ELISA 측정을 사용하여, 또는 표준 Gcase 활성 검정법에 의해 정량화될 수 있다.
실시예 3: 돌연변이체 마우스를 이용한 생체내 검정법
본 실시예는 돌연변이체 마우스를 이용한 AAV 벡터에 관한 생체내 검정법을 기술한다. 돌연변이체 마우스에서의 상기와 같은 AAV 벡터에 관한 생체내 연구는 예를 들어, 문헌 [Liou et al. (2006) J. Biol. Chem. 281(7): 4242-4253], [Sun et al. (2005) J. Lipid Res. 46:2102-2113], 및 [Farfel-Becker et al. (2011) Dis. Model Mech. 4(6):746-752]에 의해 기술된 검정법을 이용하여 수행된다.
예를 들어, 5-10 ㎕의 주사 부피로 진한 AAV 스톡을 사용하여 (예컨대, 2x1011 vg/마우스 용량의) 비히클 대조군 및 AAV 벡터의 경막내 또는 뇌실내 전달을 수행한다. 컨벡션 강화 전달법에 의한 실질내 전달을 수행한다.
처리는 증상 발병 이전 또는 발병 이후에 개시한다. 측정되는 종점은 CNS 및 CSF 중 기질 축적, ELISA에 의한 Gcase 효소 축적 및 효소 활성의 축적, 운동 및 인지 종점, 리소좀 기능장애, 및 α-시누클레인 단량체, 원시섬유 또는 원섬유의 축적이다.
실시예 4: 질환의 화학적 모델
본 실시예는 화학적으로 유도된 고셰병을 앓는 마우스 모델 (예컨대, CBE 마우스 모델)을 이용하는 AAV 벡터에 관한 생체내 검정법을 기술한다. 예를 들어, 문헌 [Vardi et al. (2016) J Pathol. 239(4):496-509]에 기술된 바와 같이, 화학적으로 유도된 고셰병을 앓는 마우스 모델에서 상기 AAV 벡터에 관한 생체내 연구를 수행한다.
예를 들어, 5-10 ㎕의 주사 부피로 진한 AAV 스톡을 사용하여 (예컨대, 2x1011 vg/마우스의) 비히클 대조군 및 AAV 벡터의 경막내 또는 뇌실내 전달을 수행한다. 컨벡션 강화 전달법에 의한 실질내 전달을 수행한다. 꼬리 정맥 주사에 의해 말초 전달을 달성한다.
처리는 증상 발병 이전 또는 발병 이후에 개시한다. 측정되는 종점은 CNS 및 CSF 중 기질 축적, ELISA에 의한 Gcase 효소 축적 및 효소 활성의 축적, 운동 및 인지 종점, 리소좀 기능장애, 및 α-시누클레인 단량체, 원시섬유 또는 원섬유의 축적이다.
실시예 5: PD, LBD, 고셰병 환자에서의 임상 시험
일부 실시양태에서, 특정 형태의 고셰병 (예컨대, GD1)을 앓는 환자는 파킨슨병 (PD) 또는 루이소체 치매 (LBD)가 발생할 위험이 증가되어 있다. 본 실시예는 고셰병, PD 및/또는 LBD를 앓는 환자에서 본 개시내용에 의해 기술된 바와 같은 rAAV의 안전성 및 효능을 사정하는 임상 시험을 기술한다.
문헌 [Grabowski et al. (1995) Ann. Intern. Med. 122(1):33-39]에 기술된 것과 유사한 연구 디자인을 사용하여 고셰병, PD 및/또는 LBD 치료를 위한 상기 벡터의 임상 시험을 수행한다.
실시예 6: 말초 질환 치료
일부 실시양태에서, 예를 들어, 문헌 [Biegstraaten et al. (2010) Brain 133(10):2909-2919]에 기술된 바와 같이, 특정 형태의 고셰병을 앓는 환자는 말초 신경병증의 증상을 보인다.
본 실시예는 고셰병 (예컨대, 타입 1 고셰병)과 연관된 말초 신경병증의 치료를 위한 본원에 기술된 바와 같은 AAV 벡터에 관한 생체내 검정법을 기술한다. 간략하면, 말초 신경병증의 징후 또는 증상을 앓는 것으로 확인된 타입 1 고셰병 환자는 본 개시내용에 의해 기술된 바와 같은 rAAV를 투여받는다. 일부 실시양태에서, rAAV의 투여 후에, 예를 들어, 문헌 [Biegstraaten et al.]에 기술된 방법을 사용하여 대상체의 말초 신경병증 징후 및 증상을 모니터링한다.
환자에 (예컨대, 환자의 혈청에, 환자의 말초 조직에 (예컨대, 간 조직, 비장 조직 등에) 존재하는 본 개시내용에 의해 기술된 바와 같은 형질도입된 유전자 생성물의 수준을 예를 들어, 웨스턴 블롯 분석, 효소 기능성 검정법, 또는 영상화 연구에 의해 검정한다.
실시예 7: CNS 형태의 치료
본 실시예는 CNS 형태의 고셰병의 치료를 위한 본원에 기술된 바와 같은 rAAV 벡터에 관한 생체내 검정법을 기술한다. 간략하면, CNS 형태의 고셰병 (예컨대, 타입 2 또는 타입 3 고셰병)을 앓는 것으로 확인된 고셰병 환자는 본 개시내용에 의해 기술된 바와 같은 rAAV를 투여받는다. 환자의 CNS에 (예컨대, 환자의 CNS의 혈청에, 환자의 뇌척수액 (CSF)에, 또는 환자의 CNS 조직에) 존재하는 본 개시내용에 의해 기술된 바와 같은 형질도입된 유전자 생성물의 수준을 예를 들어, 웨스턴 블롯 분석, 효소 기능성 검정법, 또는 영상화 연구에 의해 검정한다.
실시예 8: SCNA 및 TMEM106B shRNA 구축물 시험
HEK293 세포
본 연구에서는 인간 배아 신장 293 세포주 (HEK293) (#85120602, 시그마-알드리치(Sigma-Aldrich)를 사용하였다. HEK293 세포를, 100 유닛/ml 페니실린 및 100 ㎍/ml 스트렙토마이신 (#15140122, 써모 피셔 사이언티픽(Thermo Fisher Scientific))을 함유하는, 10% 우태아 혈청 [FBS] [#10082147, 써모 피셔 사이언티픽])으로 보충된 배양 배지 (D-MEM [#11995065, 써모 피셔 사이언티픽] 중에서 유지시켰다.
플라스미드 형질감염
제조사의 설명서에 따라 리포펙타민(Lipofectamine) 2000 형질감염 시약 (#11668019, 써모 피셔 사이언티픽)을 이용하여 플라스미드 형질감염을 수행하였다. 간략하면, HEK293 세포 (#12022001, 시그마-알드리치)를 항생제가 없는 배양 배지 중에 3x105개의 세포/ml인 밀도로 플레이팅하였다. 다음날, 플라스미드 및 리포펙타민 2000 시약을 옵티-MEM(Opti-MEM) 용액 (#31985062, 써모 피셔 사이언티픽) 중에서 조합하였다. 5분 후, 혼합물을 HEK293 배양물에 첨가하였다. 72시간 후, RNA 또는 단백질 추출을 위해 세포를 수거하거나, 또는 세포에 대해 영상화 분석을 수행하였다. 영상화 분석을 위해, 세포 플레이팅 이전에 플레이트를 0.01% 폴리-L-리신 용액 (P8920, 시그마-알드리치)으로 미리 코팅하였다.
정량적 실시간 PCR (qRT-PCR)에 의한 유전자 발현 분석
제조사의 설명서에 따라 파워 SYBR 그린 셀-투-CT 키트(Power SYBR Green Cells-to-CT Kit) (#4402955, 써모 피셔 사이언티픽)를 이용하여 정량적 실시간 PCR (qRT-PCR)에 의해 상대적인 유전자 발현 수준을 측정하였다. 리포펙타민 2000 형질감염 시약을 이용하여 48 웰 플레이트 상에 플레이팅된 HEK293 세포 (7.5x104개의 세포/웰) 내로 후보 플라스미드를 일시적으로 형질감염시켰다 (50 ㎕ 옵티-MEM 용액 중 0.5 ㎍ 플라스미드 및 1.5 ㎕ 시약). 72시간 후, 세포로부터 RNA를 추출하고, 역전사를 위해 사용하여 제조사의 설명서에 따라 cDNA를 합성하였다. 정량적 PCR 분석을 위해, 파워 SYBR 그린 PCR 마스터 믹스(Power SYBR Green PCR Master Mix) (#4367659, 써모 피셔 사이언티픽)와 함께 유전자 특이적 프라이머 쌍 (최종 농도 250 nM)을 이용하여 2~5 ㎕의 cDNA 생성물을 이중으로 증폭시켰다. SNCA, TMEM106B, 및 GAPDH 유전자에 대한 프라이머 서열은 5'- AAG AGG GTG TTC TCT ATG TAG GC -3' (서열식별번호 64), 5'- GCT CCT CCA ACA TTT GTC ACT T -3' (서열식별번호 65) (SNCA에 대한 것), 5'-ACA CAG TAC CTA CCG TTA TAG CA-3' (서열식별번호 66), 5'-TGT TGT CAC AGT AAC TTG CAT CA-3' (서열식별번호 67) (TMEM106B에 대한 것), 및 5'- CTG GGC TAC ACT GAG CAC C -3' (서열식별번호 68), 5'- AAG TGG TCG TTG AGG GCA ATG -3' (서열식별번호 69) (GAPDH에 대한 것)이었다. 콴트스튜디오 3 리얼-타임 PCR 시스템(QuantStudio 3 Real-Time PCR system) (써모 피셔 사이언티픽)에서 정량적 PCR을 수행하였다. 하우스키핑 유전자 GAPDH에 의해 발현 수준을 정규화하였고, 비교 CT 방법을 이용하여 계산하였다.
형광 영상화 분석
SNCA 및 TMEM106B 넉다운 플라스미드를 확인하는 데 EGFP 코딩 영역 하류의 인간 SNCA 유전자의 3'-UTR을 함유하는 EGFP 리포터 플라스미드를 사용하였다. EGFP 리포터 플라스미드 및 후보 넉다운 플라스미드를 리포펙타민 2000 형질감염 시약을 이용하여, 폴리-L-리신으로 코팅된 96 웰 플레이트 상에 플레이팅된 HEK293 세포 (3.0 x104개의 세포/웰) 내로 동시에 형질감염시켰다 (10 ㎕ 옵티-MEM 용액 중 0.04 ㎍ 리포터 플라스미드, 0.06 ㎍ 넉다운 플라스미드 및 0.3 ㎕ 시약). 72시간 후, 배리오스칸 LUX(Varioskan LUX) 다중모드 판독기 (써모 피셔 사이언티픽)를 이용하여 여기 488 nm/방출 512 nm에서 EGFP 신호의 형광 강도를 측정하였다. 세포를 RT에서 10분 동안 4% PFA로 고정시키고, 40 ㎍/ml 7-아미노액티노마이신 D (7-AAD)를 함유하는 D-PBS와 함께 RT에서 30 min 동안 인큐베이션시켰다. D-PBS로 세척한 후, 배리오스칸 판독기를 이용하여 여기 546 nm/방출 647 nm에서 7-AAD 신호의 형광 강도를 측정하여 세포 개수를 정량화하였다. 7-AAD 신호 수준에 대해 정규화된 EGFP 신호를 대조군 넉다운 샘플과 비교하였다.
효소-결합된 면역흡착 검정법 (ELISA)
단백질 수준으로 넉다운 플라스미드를 확인하는 데 SNCA 코딩 영역 하류의 인간 SNCA 유전자 또는 TMEM106B 유전자의 3'-UTR을 함유하는 α-시누클레인 리포터 플라스미드를 사용하였다. HEK293 세포로부터 추출된 용해물을 이용하여 ELISA (#KHB0061, 써모 피셔 사이언티픽)에 의해 α-시누클레인 단백질의 수준을 측정하였다. 후보 플라스미드를 리포펙타민 2000 형질감염 시약을 이용하여, 48 웰 플레이트 상에 플레이팅된 HEK293 세포 (7.5 x104개의 세포/웰) 내로 일시적으로 형질감염시켰다 (25 ㎕ 옵티-MEM 용액 중 0.1 ㎍ 리포터 플라스미드, 0.15 ㎍ 넉다운 플라스미드 및 0.75 ㎕ 시약). 72시간 후, 프로테아제 억제제 칵테일 (#P8340, 시그마-알드리치)로 보충된 방사성면역침전 검정법 (RIPA) 완충제 (#89900, 써모 피셔 사이언티픽) 중에서 세포를 용해시키고, 몇 초 동안 초음파 처리하였다. 얼음 상에서 30 min 동안 인큐베이션시킨 후, 용해물을 4℃에서 15 min 동안 20,000 x g로 원심분리하고, 상청액을 수집하였다. 단백질 수준을 정량화하였다. 배리오스칸 플레이트 판독기 중 450 nm에서 플레이트를 판독하고, 소프트맥스 프로 5(SoftMax Pro 5) 소프트웨어를 이용하여 농도를 계산하였다. 측정된 단백질 농도를 비신코닌산 검정법 (#23225, 써모 피셔 사이언티픽)을 이용하여 측정된 전체 단백질 농도로 정규화하였다.
도 14 및 하기 표 3은 GFP 리포터 검정법 (상단) 및 α-Syn 검정법 (하단)에 의해, 시험관내에서 SCNA의 침묵화가 성공적으로 이루어졌다는 것을 나타내는 대표적인 데이터를 보여주는 것이다. 도 15 및 하기 표 4는 GFP 리포터 검정법 (상단) 및 α-Syn 검정법 (하단)에 의해, 시험관내에서 TMEM106B의 침묵화가 성공적으로 이루어졌다는 것을 나타내는 대표적인 데이터를 보여주는 것이다.
<표 3>
<표 4>
실시예 9: ITR "D" 서열 배치 및 세포 형질도입
ITR "D" 서열의 배치가 rAAV 벡터의 세포 형질도입에 미치는 효과를 조사하였다. 도 20에 제시된 바와 같은, 1) 야생형 ITR (예컨대, 트랜스진 인서트에 인접하게 위치하고, ITR의 말단에는 원위에 위치하는 "D" 서열) 또는 2) "D" 서열이 벡터의 "외부"에 위치하는 ITR (예컨대, ITR의 말단에 인접하게 위치하고, 트랜스진 인서트에는 원위에 위치하는 "D" 서열)을 갖는 Gcase 코딩 rAAV를 HEK293 세포에 형질도입시켰다. 놀랍게도, 데이터는 "외부" 위치에 위치하는 "D" 서열을 갖는 rAAV가 효율적으로 패키징될 수 있고, 세포를 형질도입시킬 수 있는 능력을 보유한다는 것을 나타낸다 (도 17).
등가물
본 출원은 하기 문헌의 내용, 그 전문을 참조로 포함한다: 2018년 10월 3일 출원된, 대리인 사건 번호 P1094.70002WO00으로 언급되는 국제 PCT 출원; 2018년 10월 3일 출원된, 대리인 사건 번호 P1094.70003WO00으로 언급되는 국제 PCT 출원; 2017년 10월 3일 출원된 가출원 일련 번호 62/567,296 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS"); 2017년 10월 3일 출원된 가출원 일련 번호 62/567,311 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS"); 2017년 10월 3일 출원된 가출원 일련 번호 62/567,319 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS"); 2017년 10월 3일 출원된 가출원 일련 번호 62/567,301 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS"); 2017년 10월 3일 출원된 가출원 일련 번호 62/567,310 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS"); 2017년 10월 3일 출원된 가출원 일련 번호 62/567,303 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS"); 및 2017년 10월 3일 출원된 가출원 일련 번호 62/567,305 (발명의 명칭: "GENE THERAPIES FOR LYSOSOMAL DISORDERS").
따라서, 본 발명의 적어도 하나의 실시양태의 여러 측면을 기술하였는 바, 관련 기술분야의 통상의 기술자는 다양한 변경, 변형 및 개선을 쉽게 착안해 낼 수 있음을 이해하여야 한다. 상기 변경, 변형 및 개선은 본 개시내용의 일부가 되는 것으로 의도되고, 본 발명의 정신 및 범주 내에 포함되는 것으로 의도된다. 따라서, 상기 설명 및 도면은 단지 예일 뿐이다.
본원에 본 발명의 여러 실시양태가 기술되고, 예시되었지만, 관련 기술분야의 통상의 기술자는 기능을 수행하고/거나, 본원에 기술된 결과 및/또는 이점들 중 하나 이상의 것을 수득하기 위해 각종의 다른 수단 및/또는 구조를 쉽게 구상해 낼 수 있을 것이며, 상기 변이 및/또는 변형은 각각 본 발명의 범주 내에 포함되는 것으로 간주된다. 더욱 일반적으로, 관련 기술분야의 통상의 기술자는 본원에 기술된 모든 파라미터, 치수, 물질 및 구성은 예시적인 것임을 의미하며, 실제 파라미터, 치수, 물질 및/또는 구성은 본 발명의 교시(들)가 사용되는 구체적인 적용 또는 적용들에 의존하게 된다는 것을 쉽게 이해할 것이다. 관련 기술분야의 통상의 기술자는 단지 통상의 실험만을 사용하고도, 본원에 기술된 본 발명의 구체적인 실시양태에 대한 다수의 등가물을 쉽게 이해하거나, 또는 확인할 수 있을 것이다. 그러므로, 상기 실시양태는 단지 예시로서 제공되는 것이며, 첨부된 청구범위 및 그의 등가물의 범주 내에서 본 발명은 구체적으로 기술되고, 청구된 것과 다르게 실시될 수 있다는 것을 이해하여야 한다. 본 발명은 본원에 기술된 각각의 개별 특징, 시스템, 물품, 물질, 및/또는 방법에 관한 것이다. 추가로, 상기 특징, 시스템, 물품, 물질, 및/또는 방법이 서로 모순되지 않는다면, 둘 이상의 상기 특징, 시스템, 물품, 물질, 및/또는 방법의 임의의 조합이 본 발명의 범주 내에 포함된다.
명세서 중 및 청구범위 중 본원에서 사용되는 바, "단수형태"는 달리 명확하게 그 반대로 명시되지 않는 한, "적어도 하나"를 의미하는 것으로 이해되어야 한다.
명세서 중 및 청구범위 중 본원에서 사용되는 바, "및/또는"이라는 어구는 그렇게 결합되어 있는 요소 중 "어느 하나 또는 그 둘 모두," 즉, 일부 경우에서는 공동으로 존재하고, 다른 경우에는 분리되어 존재하는 요소를 의미하는 것으로 이해되어야 한다. 달리 명확하게 그 반대로 명시되지 않는 한, 구체적으로 확인된 요소와 관련이 있든 또는 관련이 없든 상관없이, "및/또는" 절에 의해 구체적으로 확인된 요소 이외의 다른 요소가 임의적으로 존재할 수 있다. 따라서, 비제한적인 예로서, 예컨대, "포함하는"이라는 제한을 두지 않은 개방형의 표현과 함께 결합하여 사용될 때, "A 및/또는 B"라고 언급하는 것은 한 실시양태에서는 (임의적으로 B 이외의 다른 요소를 포함하면서) B 없이 A를 지칭할 수 있고; 또 다른 실시양태에서는 (임의적으로 A 이외의 다른 요소를 포함하면서) A 없이 B를 지칭할 수 있고; 추가의 또 다른 실시양태에서는 (임의적으로 다른 요소를 포함하면서) A 및 B, 둘 모두를 지칭할 수 있으며; 기타의 경우도 존재할 수 있다.
명세서 중 및 청구범위 중 본원에서 사용되는 바, "또는"은 상기 정의된 "및/또는"과 동일한 의미를 갖는 것으로 이해되어야 한다. 예를 들어, 목록에서 항목을 분리할 때, "또는" 또는 "및/또는"은 포괄적인 의미로, 즉, 요소의 개수 또는 요소의 목록 중 적어도 하나를 포함할 뿐만 아니라, 그 중 1개 초과의 것을 포함하고, 열거되지 않은 추가 항목을 포함하는 것으로 해석되어야 한다. 그 반대로 명확하게 명시된 용어, 예컨대, "~중 단 하나만" 또는 "~중 정확하게 하나," 또는 청구범위에서 사용될 때, "~으로 이루어진"이라는 용어만이 요소의 개수 또는 요소의 목록 중 정확히 하나의 요소를 포함하는 것을 의미할 것이다. 일반적으로, 본원에서 사용되는 바, "또는"이라는 용어는 오직, 배타적인 용어, 예컨대, "둘 중 어느 하나," "~중 하나," "~중 단 하나만" 또는 "~중 정확하게 하나"라는 용어가 선행될 때 배타적인 대안 (즉, "하나 또는 나머지 다른 하나이지만, 그 둘 모두는 아닌 것")을 나타내는 것으로 해석되어야한다. 청구범위에서 사용될 때, "본질적으로 ~으로 이루어진"이라는 것은 특허법 분야에서 사용되는 바와 같이, 그의 일반적인 의미를 가져야 한다.
본원, 본 명세서 및 청구범위에서 사용되는 바, 하나 이상의 요소의 목록과 관련하여, "적어도 하나의"라는 어구는, 반드시 요소의 목록 내에 구체적으로 열거된 각각의 모든 요소 중 적어도 하나를 포함하여야 하는 것이 아니라, 요소의 목록에서 요소의 임의의 조합을 배제하는 것이 아니라, 적어도 하나의 요소가 요소의 목록에서 요소 중 임의의 하나 이상의 것으로부터 선택된다는 것을 의미하는 것으로 이해되어야 한다. 상기 정의는 또한, 구체적으로 확인된 요소와 관련이 있든 또는 없든 그에 상관없이, "적어도 하나의"라는 어구가 지칭하는 요소의 목록 내에 구체적으로 확인된 요소 이외의 요소가 임의적으로 존재할 수 있다는 것도 허용한다. 따라서, 비제한적인 예로서, "A 및 B 중 적어도 하나의" (또는 동일하게, "A 또는 B 중 적어도 하나의," 또는 동일하게, "A 및/또는 B 중 적어도 하나의")라는 것은 한 실시양태에서는 (임의적으로 B 이외의 다른 요소를 포함하면서) B는 존재하지 않고, 임의적으로 1개 초과의 A를 포함하는 적어도 하나의 A를 지칭할 수 있고; 또 다른 실시양태에서는, (임의적으로 A 이외의 다른 요소를 포함하면서) A는 존재하지 않고, 임의적으로 1개 초과의 B를 포함하는 적어도 하나의 B를 지칭할 수 있고; 추가의 또 다른 실시양태에서, 임의적으로 1개 초과의 A를 포함하는 적어도 하나의 A, 및 임의적으로 1개 초과의 B를 포함하는 적어도 하나의 B (및 다른 요소를 포함하는 것) 등을 칭할 수 있다.
상기 명세서 뿐만 아니라, 청구항에서, 예컨대, "포함하는," "비롯한," "보유하는," "갖는," "함유하는," "수반하는," "보유하는" 등의 모든 전환 어구는 제한을 두지 않은 개방형인 것으로, 즉, ~을 포함하나, 이에 제한되지 않는다는 것을 의미하는 것으로 이해되어야 한다. 미국 특허청의 심사 절차에 관한 매뉴얼, 섹션 2111.03(United States Patent Office Manual of Patent Examining Procedures, Section 2111.03)에 기재되어 있는 바와 같이, 오직 "~으로 이루어진" 및 "본질적으로 ~으로 이루어진"이라는 전환 어구만이 각각 폐쇄형 또는 반-폐쇄형 전환 어구여야 한다.
청구항 중의 청구항을 수식하는 서수 용어, 예컨대, "제1," "제2," "제3" 등의 사용은 그 단독으로 한 청구항의 또 다른 청구항 대비의 임의의 우선함, 우위임, 또는 순서, 또는 방법의 조치가 수행되는 시간적 순서를 내포하는 것이 아니라, 이는 단지 청구항을 구별하기 위해 특정명을 갖는 한 청구항을 동일명을 갖는 또 다른 항을 구별하는 (서수 용어의 사용을 위한) 라벨로서 사용된다.
명백하게 반대로 명시되지 않는 한, 1개 초과의 단계 또는 조치를 포함하는 본원에서 청구되는 임의의 방법에서, 본 방법의 단계 또는 조치의 순서가 반드시 본 방법의 단계 또는 조치가 언급된 순서로 제한되는 것은 아니라는 것도 또한 이해하여야 한다.
서열
일부 실시양태에서, 하나 이상의 유전자 생성물 (예컨대, 제1, 제2 및/또는 제3 유전자 생성물)을 코딩하는 단리된 핵산, rAAV 벡터, 또는 유전자 발현 카세트는 서열식별번호 1-69 중 어느 하나에 기재된 서열을 포함하거나 또는 그로 이루어진다 (또는 상기 서열을 갖는 펩티드를 코딩한다). 일부 실시양태에서, 유전자 생성물은 서열식별번호 1-69 중 어느 하나의 일부 (예컨대, 단편)에 의해 코딩된다.
SEQUENCE LISTING
<110> Prevail Threapeutics, Inc.
<120> GENE THERAPIES FOR LYSOSOMAL DISORDERS
<130> P1094.70004WO00
<140> Not Yet Assigned
<141> Concurrently herewith
<150> US 62/567,305
<151> 2017-10-03
<150> US 62/567,303
<151> 2017-10-03
<160> 69
<170> PatentIn version 3.5
<210> 1
<211> 3022
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 1
attctggtgt gatccaggaa cagctgtctt ccagctctga aagagtgtgg tgtaaaggaa 60
ttcattagcc atggatgtat tcatgaaagg actttcaaag gccaaggagg gagttgtggc 120
tgctgctgag aaaaccaaac agggtgtggc agaagcagca ggaaagacaa aagagggtgt 180
tctctatgta ggctccaaaa ccaaggaggg agtggtgcat ggtgtggcaa cagtggctga 240
gaagaccaaa gagcaagtga caaatgttgg aggagcagtg gtgacgggtg tgacagcagt 300
agcccagaag acagtggagg gagcagggag cattgcagca gccactggct ttgtcaaaaa 360
ggaccagttg ggcaagaatg aagaaggagc cccacaggaa ggaattctgg aagatatgcc 420
tgtggatcct gacaatgagg cttatgaaat gccttctgag gaagggtatc aagactacga 480
acctgaagcc taagaaatat ctttgctccc agtttcttga gatctgctga cagatgttcc 540
atcctgtaca agtgctcagt tccaatgtgc ccagtcatga catttctcaa agtttttaca 600
gtgtatctcg aagtcttcca tcagcagtga ttgaagtatc tgtacctgcc cccactcagc 660
atttcggtgc ttccctttca ctgaagtgaa tacatggtag cagggtcttt gtgtgctgtg 720
gattttgtgg cttcaatcta cgatgttaaa acaaattaaa aacacctaag tgactaccac 780
ttatttctaa atcctcacta tttttttgtt gctgttgttc agaagttgtt agtgatttgc 840
tatcatatat tataagattt ttaggtgtct tttaatgata ctgtctaaga ataatgacgt 900
attgtgaaat ttgttaatat atataatact taaaaatatg tgagcatgaa actatgcacc 960
tataaatact aaatatgaaa ttttaccatt ttgcgatgtg ttttattcac ttgtgtttgt 1020
atataaatgg tgagaattaa aataaaacgt tatctcattg caaaaatatt ttatttttat 1080
cccatctcac tttaataata aaaatcatgc ttataagcaa catgaattaa gaactgacac 1140
aaaggacaaa aatataaagt tattaatagc catttgaaga aggaggaatt ttagaagagg 1200
tagagaaaat ggaacattaa ccctacactc ggaattccct gaagcaacac tgccagaagt 1260
gtgttttggt atgcactggt tccttaagtg gctgtgatta attattgaaa gtggggtgtt 1320
gaagacccca actactattg tagagtggtc tatttctccc ttcaatcctg tcaatgtttg 1380
ctttacgtat tttggggaac tgttgtttga tgtgtatgtg tttataattg ttatacattt 1440
ttaattgagc cttttattaa catatattgt tatttttgtc tcgaaataat tttttagtta 1500
aaatctattt tgtctgatat tggtgtgaat gctgtacctt tctgacaata aataatattc 1560
gaccatgaat aaaaaaaaaa aaaaagtggg ttcccgggaa ctaagcagtg tagaagatga 1620
ttttgactac accctcctta gagagccata agacacatta gcacatatta gcacattcaa 1680
ggctctgaga gaatgtggtt aactttgttt aactcagcat tcctcacttt ttttttttaa 1740
tcatcagaaa ttctctctct ctctctctct ttttctctcg ctctcttttt tttttttttt 1800
ttacaggaaa tgcctttaaa catcgttgga actaccagag tcaccttaaa ggagatcaat 1860
tctctagact gataaaaatt tcatggcctc ctttaaatgt tgccaaatat atgaattcta 1920
ggatttttcc ttaggaaagg tttttctctt tcagggaaga tctattaact ccccatgggt 1980
gctgaaaata aacttgatgg tgaaaaactc tgtataaatt aatttaaaaa ttatttggtt 2040
tctcttttta attattctgg ggcatagtca tttctaaaag tcactagtag aaagtataat 2100
ttcaagacag aatattctag acatgctagc agtttatatg tattcatgag taatgtgata 2160
tatattgggc gctggtgagg aaggaaggag gaatgagtga ctataaggat ggttaccata 2220
gaaacttcct tttttaccta attgaagaga gactactaca gagtgctaag ctgcatgtgt 2280
catcttacac tagagagaaa tggtaagttt cttgttttat ttaagttatg tttaagcaag 2340
gaaaggattt gttattgaac agtatatttc aggaaggtta gaaagtggcg gttaggatat 2400
attttaaatc tacctaaagc agcatatttt aaaaatttaa aagtattggt attaaattaa 2460
gaaatagagg acagaactag actgatagca gtgacctaga acaatttgag attaggaaag 2520
ttgtgaccat gaatttaagg atttatgtgg atacaaattc tcctttaaag tgtttcttcc 2580
cttaatattt atctgacggt aatttttgag cagtgaatta ctttatatat cttaatagtt 2640
tatttgggac caaacactta aacaaaaagt tctttaagtc atataagcct tttcaggaag 2700
cttgtctcat attcactccc gagacattca cctgccaagt ggcctgagga tcaatccagt 2760
cctaggttta ttttgcagac ttacattctc ccaagttatt cagcctcata tgactccacg 2820
gtcggcttta ccaaaacagt tcagagtgca ctttggcaca caattgggaa cagaacaatc 2880
taatgtgtgg tttggtattc caagtggggt ctttttcaga atctctgcac tagtgtgaga 2940
tgcaaacatg tttcctcatc tttctggctt atccagtatg tagctatttg tgacataata 3000
aatatataca tatatgaaaa ta 3022
<210> 2
<211> 6514
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 2
aggcgcggac gcaggttaca gcagcgcttg gcctctgctg atgccgtcgt tatcctaccc 60
ctcccccgtc ccagctctac ggcggccgcg cgctccaggc cggtcgctcc accccccggc 120
tcccgggact gtggactcca cgaccctgtc ctcggccctg tccgcgccga agcagcccgg 180
gactgcgcag cgccccgcgt gccgatcttt tcctaattca gcagcgattt aaccaagagc 240
ctggaatatt ttaaggagta ataagagaca tttacaaact attctctctg aagcctgcta 300
cctggaggca tcatctagat aatcagaacc ttggcttcca catcctcctc ccttgtctta 360
actacaaaca tttctttctg ctgacttcaa ctcctcagac atgggaaagt ctctttctca 420
tttgcctttg cattcaagca aagaagatgc ttatgatgga gtcacatctg aaaacatgag 480
gaatggactg gttaatagtg aagtccataa tgaagatgga agaaatggag atgtctctca 540
gtttccatat gtggaattta caggaagaga tagtgtcacc tgccctactt gtcagggaac 600
aggaagaatt cctagggggc aagaaaacca actggtggca ttgattccat atagtgatca 660
gagattaagg ccaagaagaa caaagctgta tgtgatggct tctgtgtttg tctgtctact 720
cctttctgga ttggctgtgt ttttcctttt ccctcgctct atcgacgtga aatacattgg 780
tgtaaaatca gcctatgtca gttatgatgt tcagaagcgt acaatttatt taaatatcac 840
aaacacacta aatataacaa acaataacta ttactctgtc gaagttgaaa acatcactgc 900
ccaagttcaa ttttcaaaaa cagttattgg aaaggcacgc ttaaacaaca taaccattat 960
tggtccactt gatatgaaac aaattgatta cacagtacct accgttatag cagaggaaat 1020
gagttatatg tatgatttct gtactctgat atccatcaaa gtgcataaca tagtactcat 1080
gatgcaagtt actgtgacaa caacatactt tggccactct gaacagatat cccaggagag 1140
gtatcagtat gtcgactgtg gaagaaacac aacttatcag ttggggcagt ctgaatattt 1200
aaatgtactt cagccacaac agtaaaaact ggaagagatg gatttaaaga agaaatatct 1260
attgatattt cctatactct caatgaagag gtatttccta ataggagacc ttaaattgaa 1320
caaacctaaa gtttacactt ctaagagtac agttaaaagt atgtggacct gcagttcttg 1380
taactctcca ctctgtgtta atgatatatt tgtactagga tcttttactt gaatctaaat 1440
ttactggttg atttccttct ccagcctatc ccctacaggg aaaagctgat acttccccta 1500
tagtacaata aataattatt taaaagtcat agctccagtc actactgaaa acataatttt 1560
ggtgataaac ataatttgag aaacttaatt tctgaatgtt tttatagaaa attactgaaa 1620
gtctattact catggaagac ttttaaagaa taaccttttt tcctgtttta taaattccca 1680
ttgttatatg gtagtatttc agctacacaa tattttagct tttagctaga catttatagc 1740
ttttcatttg ttgaaatggt aatcatctgc atgtttttgt cacttatttc aggttagtga 1800
ttgcctaaca cttataagcc aaaataatct ttgcaaaatt ccatacctaa aattttgaaa 1860
gcccctaatg ttttcacaca tctttctgta ttagttatag ttttgtgaaa tctttgtgtg 1920
atcttcaaac attatcattt aatgtacaat actgtaaata aactgtgcat ggcttttata 1980
cagctttagt aaatgtcaaa taaagtggta cagactcatt acaacaagtt tctcataaaa 2040
atacaataaa taggaaaatg aaattcagaa acccatagac tgggaatagg ttccagttac 2100
agcttggatc tggcataaaa taaatttgaa ataaaatatt ttgatgctcc atttttttat 2160
gttgcttttc atactaaaga atggtgtaga catgttttgc aactgttagg tacccagtta 2220
tcaattttat caatgtttta gaggaggaaa ttattttttt ggtagaaatt gttcaagaaa 2280
tccttaattg aatgtcatta aatgatggtg gccaaaataa aacctattta gaaatttaat 2340
cactttgcac atcacttgga atatgatgcc tctagtagtt acttttttat agttttctac 2400
ttttggtttt atttaaaatt gttttcaaat atagattatt gacttattca actttgctgt 2460
tttatatttt cagtatcatt tttcattttt tttttttttt gtcttttcac ttaccaagtt 2520
ctagggacat ttaaaatatg tactaagtgt aggagtggtt atgataccaa aaaatgtagc 2580
tgggttgaga ttaatttcgt tctgttttct catgacagaa atcaggtttc cctttcccca 2640
cccctaagtg cctaacttag gtctgaaaca gcctgtttat tagtctgact ctctcaacca 2700
taaaacataa gctttattta attctgcctt taaacacact caggtttccc cttaattttc 2760
atattatttt ctgcaagttt tcttgagtat cttcaattcg ttgaatgtgg tttttggttt 2820
ttttttgttt taacactagt cttcccttaa ttcattgcta actcaagcca tccttactat 2880
taaacccaaa tcagtccttt aagttcatta tggcctttct agtatttaaa aaaaaaaaaa 2940
tcattttcat ttttcttctg ctacgtttcc tgactactac tgcatacttc tctgatacag 3000
gttctgtttg tattttttat atcattctca ttttctcatt tgacatgatc tatgtctata 3060
tatgatatag gtcccctttt gtctcaaaat ttttaattat gtgacttcaa aaatcacctg 3120
tatctgtagt agggcttcca aatctgcttc tccatatgtg accagtcacc tgtctgcttt 3180
cacatttagc tagtgaacta cacatttact aaaatgtgta aattttacac atttagtgac 3240
tgtgtaaaat aaaaaaaaag ttattttatc atatcctttc tattatgttc ccatcctgtc 3300
ctcatgtccc atttacttta ttatcaccat tcatttcttc aaaattatct tttagatacg 3360
ctcatacaaa aatcaatcct tgttttcttg cttgtgtctt ttaaccttgg aaaattacat 3420
cgtgtaaatt aaacagattt ttctgatgat ctgtgcttct tatatactat tagagtgcat 3480
gatagtatct cctgaaaagg atggaaagta gaagcatttg cttttagtca cttaattttg 3540
aatctttttt cttcatcttt tgaattaatt ttttttatta tatctacttt tagtggagtt 3600
tgagtcagaa aaaaacaaga atttgaaaca agtaaaaaga tagaagagaa ataaagatgg 3660
tatgtgacta ctttcagaga gagttaagta actgtcagaa taagcctgga acaaaacagg 3720
ctgtaaatta ataaaactac aaacacacat tcaggtgaag cagaagtata gccataaaac 3780
atctagaaag agtgaatgag gcttttagct tttcttaggt caatgtccag tgtgcttttt 3840
tccatgggaa taggataggt attaatacgc ttttctaaac tgctctcaga ccttatccag 3900
aggacatggt aaagatatgt tacagaaatt tttctgatac ttcctggaat aactttaagt 3960
tacaccctag tagactggtc attctaataa aatccagtac tataacaaac ctctgtatgt 4020
tgatagcaca ttggcccttt ttagagttct ttcctatgtt tttcttacgt gatttcccac 4080
agttccatga gtccaacaaa ggagagtgat aggctcctta tcttttagaa gaggaaggaa 4140
aggcatgaag aagttgaggg actggctgaa gatcacgtac ttactaagta gtacaactgg 4200
agcaagatca agtatctctg tctcccatat ctgtgttcta tcatttaaaa tatatattgg 4260
aaatccctgc tgactcagat tggtatgatt aaaaatgaga ggaaagttca aatagttagt 4320
agtgacaaac taatactgct ggactaagat tttggtagca ttgttttcta aaatatttta 4380
aatggagaat gaacacttat aaaatgcttt ggaacataat ctttagctta attttctgtt 4440
aaaatttagt accccttcat cattccaata aagataagac tgatccattg tctaaggaaa 4500
ttatttataa ataatagaga ttaatttatt tgagatttga aataagaata gtatgaaaat 4560
attagatacc acataaattg tttgaaatta ctgaataacc atcttaagta tggaacattt 4620
aaatggctat attttatttg tgtacagttt ttctgtgcct tgttaggcca gtgaagcaat 4680
tattttctct aagaaaatga caataaaata taacacactt cagattgtct gatttacagt 4740
ttggaaagga caccgcaatg ttcaaatagg taggagacca tcaaaaacac aattaaagta 4800
acatattagg agacttgaaa cttcagccta ataaatcctt catggttctt agccttatta 4860
ttgtgatata attctagata ttttcttgga gggcatgtgc ccaactctcc cgcaccccat 4920
tttgtttgtc ttttaaagtt cttagaataa acagttcttt atataataat tatattttat 4980
ttaagaaaat agtttgttag gtacttttta aaagatgtaa atttttaaat ttacaaatac 5040
atatgggtct ttgataagca ataggaattg aattacaagt tactagggtt ataagcaaaa 5100
ggttgcttac cataatgtca ttaggtcacg atttttagct cacatctgga agcagcaact 5160
acttggctca agtacatata agagtaatta gttttattct ctctttttta taaaatcggg 5220
tttcagatga gatgtttatc ttagactatt ttagggaaaa attttacatg tttgagatgg 5280
tggagtaaaa agactgttaa acatttcttt taaaaaatta tttttacatt acaacaatat 5340
atttatgatg tgttcagatc aaaaatttaa cttctgtgtc ccagatctac tttcaaagtg 5400
agattttcac ttgtcagctt aaatttctga ctagaactaa catttgtgta tttttgtgct 5460
tagtcggaat acaaatttca cagtggattt ttgaagtttg tccttaaatt ggataaaatc 5520
aagtgattaa agttactaaa gagataaaaa tggtaatttc catttttaaa agtaatttgg 5580
ttgtgtttat agttatttgt acaagtattt atcacagact ctaaattgaa aaatgtagta 5640
tgatctatat ttgaccctaa aaatgttgga ttaatttaac aaatatggca gatttttcat 5700
aactaagtct taagtcttct aaaaggaagc tgttaccctt ctgtttttaa ttacattaat 5760
tgaaatgtgt tttaagagat acaatttcag catattttat atattaaaaa acaaaaaagg 5820
attagtattg agccagtggc caaaaggtaa tattactacc atgtagactg ttatagttca 5880
aattgtccca cttcacccag aattttagaa actagaagtc tgggaggtac tatatcagct 5940
gtagttgggt aattccaagt gctgatagta ctattcatct tttttattat tgtgtcagat 6000
gaaacaaatg ccaagttgca aaatatgcag atttttatta tataatggtt ttaggcataa 6060
attattaaca agccatgcct tatgtgtttc atcttatatt tttctttaga actaaactat 6120
aacagatttt ggaaaatgat ttgacgtgct tgctcacttg attgacttgg tcagatattt 6180
gaatgatggt attacctaga ttctaatcct tgattctagt tatataataa ataatataga 6240
atatgaaaat atgtttgggc atttactgtt tatattatgt agtagcctcc atcatgacac 6300
acttactaca tttatgaatt gagcagttct gtaattgtaa ttattattgc tgttcatgta 6360
acaaaacatg cttataatag caaacaaata gaaatgcccc caaaatgcta tttttttaat 6420
tcagttataa ctgttactct tgtagttgtg tatgacgcaa taaaatttgt aaaaaaattt 6480
cagcatgaaa aataaaattt gtatcactta tgta 6514
<210> 3
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 3
tggaagactt cgagatacac tgt 23
<210> 4
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 4
acagtgtatc tcgaagtctt cca 23
<210> 5
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 5
tttagaaata agtggtagtc a 21
<210> 6
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 6
tgactaccac ttatttctaa a 21
<210> 7
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 7
agggtatcaa gactacgaa 19
<210> 8
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 8
ttcgtagtct tgataccct 19
<210> 9
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 9
gtgtactagg atcttttact tgaa 24
<210> 10
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 10
ttcaagtaaa agatcctagt acac 24
<210> 11
<211> 267
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 11
gtgatatcac aaggtcccag ggctggggtc agaaattctc tcccgaggga atgaagccac 60
aggagccaag agcaggagga ccaaggccct ggcgaaggcc gtggcctcgt tcaagtaaaa 120
gatcctagta cagtgcaggt cccaatgtgt actaggatct tttacttgaa cggggacgcc 180
ggcatccggg ctcaggaccc ccctctctgc cagaggcacc aacaccagag ttcacaaatc 240
agtctcctgc cctttgcatg tagcaaa 267
<210> 12
<211> 267
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 12
tttgctacat gcaaagggca ggagactgat ttgtgaactc tggtgttggt gcctctggca 60
gagagggggg tcctgagccc ggatgccggc gtccccgttc aagtaaaaga tcctagtaca 120
cattgggacc tgcactgtac taggatcttt tacttgaacg aggccacggc cttcgccagg 180
gccttggtcc tcctgctctt ggctcctgtg gcttcattcc ctcgggagag aatttctgac 240
cccagccctg ggaccttgtg atatcac 267
<210> 13
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 13
tattagatct gatggccgc 19
<210> 14
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 14
ctccatcact aggggttcct 20
<210> 15
<211> 60
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 15
agctctgggt atttaagccc gagtgagcac gcagggtctc cattttgaag cgggaggtta 60
<210> 16
<211> 145
<212> DNA
<213> Unknown
<220>
<223> AAV2 ITR
<400> 16
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg 60
ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc 120
gagcgcgcag agagggagtg gccaa 145
<210> 17
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 17
ctggaggctt gctttgggct gtatgctgtg gaagacttcg agatacactg tttttggcct 60
ctgactgaac agtgttctga agtcttccac aggacacaag gccctttatc agcactcaca 120
tggaacaaat ggccaccgtg ggaggatgac aa 152
<210> 18
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 18
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctgataaagg gccttgtgtc 60
ctgtggaaga cttcagaaca ctgttcagtc agaggccaaa aacagtgtat ctcgaagtct 120
tccacagcat acagcccaaa gcaagcctcc ag 152
<210> 19
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 19
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctagtaacag gccttgtgtc 60
cttttagaaa taagtggtag tcacatctgt ggcttcactt gactaccact tatttctaaa 120
gacaacagca tacagccttc agcaagcctc ca 152
<210> 20
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 20
tggaggcttg ctgaaggctg tatgctgttg tctttagaaa taagtggtag tcaagtgaag 60
ccacagatgt gactaccact tatttctaaa aggacacaag gcctgttact agcactcaca 120
tggaacaaat ggccaccgtg ggaggatgac aa 152
<210> 21
<211> 179
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 21
tggaggcttg ctgaaggctg tatgctgttg tcctcgagtg agcgtagggt atcaagacta 60
cgaatactgt aaagccacag atgggtgttc gtagtcttga tacccttcgc ctactagagg 120
acacaaggcc tgttactagc actcacatgg aacaaatggc caccgtggga ggatgacaa 179
<210> 22
<211> 179
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 22
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctagtaacag gccttgtgtc 60
ctctagtagg cgaagggtat caagactacg aacacccatc tgtggcttta cagtattcgt 120
agtcttgata ccctacgctc actcgaggac aacagcatac agccttcagc aagcctcca 179
<210> 23
<211> 10960
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 23
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctccgg gctgtaatta 1080
gcgcttggtt taatgacggc ttgtcctggt ggcgagggga ggggggtggt cctcgaacgc 1140
cttgcagaac tggcctggat acagagtgga ccggctggcc ccatctggaa gacttcgaga 1200
tacactgttg tcttactgcg ctcaacagtg tatctcgaag tcttccaaat ggtgccagcc 1260
atcgcagcgg ggtgcaggaa atgggggcag cccccctttt tggctatcct tccacgtgtt 1320
cttttttgta tcttttgtgt ttcctagaaa acatctcagt caccaccttt ctgtggctgc 1380
gtgaaagcct tgaggggctc cgggagctag agcctctgct aaccatgttc atgccttctt 1440
ctttttccta cagctcctgg gcaacgtgct ggttattgtg ctgtctcatc attttggcaa 1500
agaattcctc gaagatccga agggaaagtc ttccacgact gtgggatccg ttcgaagata 1560
tcaccggttg agccaccatg gaattcagca gccccagcag agaggaatgc cccaagcctc 1620
tgagccgggt gtcaatcatg gccggatctc tgacaggact gctgctgctt caggccgtgt 1680
cttgggcttc tggcgctaga ccttgcatcc ccaagagctt cggctacagc agcgtcgtgt 1740
gcgtgtgcaa tgccacctac tgcgacagct tcgaccctcc tacctttcct gctctgggca 1800
ccttcagcag atacgagagc accagatccg gcagacggat ggaactgagc atgggaccca 1860
tccaggccaa tcacacaggc actggcctgc tgctgacact gcagcctgag cagaaattcc 1920
agaaagtgaa aggcttcggc ggagccatga cagatgccgc cgctctgaat atcctggctc 1980
tgtctccacc agctcagaac ctgctgctca agagctactt cagcgaggaa ggcatcggct 2040
acaacatcat cagagtgccc atggccagct gcgacttcag catcaggacc tacacctacg 2100
ccgacacacc cgacgatttc cagctgcaca acttcagcct gcctgaagag gacaccaagc 2160
tgaagatccc tctgatccac agagccctgc agctggcaca aagacccgtg tcactgctgg 2220
cctctccatg gacatctccc acctggctga aaacaaatgg cgccgtgaat ggcaagggca 2280
gcctgaaagg ccaacctggc gacatctacc accagacctg ggccagatac ttcgtgaagt 2340
tcctggacgc ctatgccgag cacaagctgc agttttgggc cgtgacagcc gagaacgaac 2400
cttctgctgg actgctgagc ggctacccct ttcagtgcct gggctttaca cccgagcacc 2460
agcgggactt tatcgcccgt gatctgggac ccacactggc caatagcacc caccataatg 2520
tgcggctgct gatgctggac gaccagagac tgcttctgcc ccactgggct aaagtggtgc 2580
tgacagatcc tgaggccgcc aaatacgtgc acggaatcgc cgtgcactgg tatctggact 2640
ttctggcccc tgccaaggcc acactgggag agacacacag actgttcccc aacaccatgc 2700
tgttcgccag cgaagcctgt gtgggcagca agttttggga acagagcgtg cggctcggca 2760
gctgggatag aggcatgcag tacagccaca gcatcatcac caacctgctg taccacgtcg 2820
tcggctggac cgactggaat ctggccctga atcctgaagg cggccctaac tgggtccgaa 2880
acttcgtgga cagccccatc atcgtggaca tcaccaagga caccttctac aagcagccca 2940
tgttctacca cctgggacac ttcagcaagt tcatccccga gggctctcag cgcgttggac 3000
tggtggcttc ccagaagaac gatctggacg ccgtggctct gatgcaccct gatggatctg 3060
ctgtggtggt ggtcctgaac cgcagcagca aagatgtgcc cctgaccatc aaggatcccg 3120
ccgtgggatt cctggaaaca atcagccctg gctactccat ccacacctac ctgtggcgta 3180
gacagtgaca attgttaatt aagtttaaac cctcgaggcc gcaagcttat cgataatcaa 3240
cctctggatt acaaaatttg tgaaagattg actggtattc ttaactatgt tgctcctttt 3300
acgctatgtg gatacgctgc tttaatgcct ttgtatcatg ctattgcttc ccgtatggct 3360
ttcattttct cctccttgta taaatcctgg ttgctgtctc tttatgagga gttgtggccc 3420
gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg acgcaacccc cactggttgg 3480
ggcattgcca ccacctgtca gctcctttcc gggactttcg ctttccccct ccctattgcc 3540
acggcggaac tcatcgccgc ctgccttgcc cgctgctgga caggggctcg gctgttgggc 3600
actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct ttccttggct gctcgcctgt 3660
gttgccacct ggattctgcg cgggacgtcc ttctgctacg tcccttcggc cctcaatcca 3720
gcggaccttc cttcccgcgg cctgctgccg gctctgcggc ctcttccgcg tcttcgcctt 3780
cgccctcaga cgagtcggat ctccctttgg gccgcctccc cgcatcgata ccgtcgacta 3840
gagctcgctg atcagcctcg actgtgcctt ctagttgcca gccatctgtt gtttgcccct 3900
cccccgtgcc ttccttgacc ctggaaggtg ccactcccac tgtcctttcc taataaaatg 3960
aggaaattgc atcgcattgt ctgagtaggt gtcattctat tctggggggt ggggtggggc 4020
aggacagcaa gggggaggat tgggaagaca atagcaggca tgctggggag agatccacga 4080
taacaaacag cttttttggg gtgaacatat tgactgaatt ccctgcaggt tggccactcc 4140
ctctctgcgc gctcgctcgc tcactgaggc cgcccgggca aagcccgggc gtcgggcgac 4200
ctttggtcgc ccggcctcag tgagcgagcg agcgcgcaga gagggagtgg ccaactccat 4260
cactaggggt tcctgcggcc gctcgtacgg tctcgaggaa ttcctgcagg ataacttgcc 4320
aacctcattc taaaatgtat atagaagccc aaaagacaat aacaaaaata ttcttgtaga 4380
acaaaatggg aaagaatgtt ccactaaata tcaagattta gagcaaagca tgagatgtgt 4440
ggggatagac agtgaggctg ataaaataga gtagagctca gaaacagacc cattgatata 4500
tgtaagtgac ctatgaaaaa aatatggcat tttacaatgg gaaaatgatg gtctttttct 4560
tttttagaaa aacagggaaa tatatttata tgtaaaaaat aaaagggaac ccatatgtca 4620
taccatacac acaaaaaaat tccagtgaat tataagtcta aatggagaag gcaaaacttt 4680
aaatctttta gaaaataata tagaagcatg cagaccagcc tggccaacat gatgaaaccc 4740
tctctactaa taataaaatc agtagaacta ctcaggacta ctttgagtgg gaagtccttt 4800
tctatgaaga cttctttggc caaaattagg ctctaaatgc aaggagatag tgcatcatgc 4860
ctggctgcac ttactgataa atgatgttat caccatcttt aaccaaatgc acaggaacaa 4920
gttatggtac tgatgtgctg gattgagaag gagctctact tccttgacag gacacatttg 4980
tatcaactta aaaaagcaga tttttgccag cagaactatt cattcagagg taggaaactt 5040
agaatagatg atgtcactga ttagcatggc ttccccatct ccacagctgc ttcccaccca 5100
ggttgcccac agttgagttt gtccagtgct cagggctgcc cactctcagt aagaagcccc 5160
acaccagccc ctctccaaat atgttggctg ttccttccat taaagtgacc ccactttaga 5220
gcagcaagtg gatttctgtt tcttacagtt caggaaggag gagtcagctg tgagaacctg 5280
gagcctgaga tgcttctaag tcccactgct actggggtca gggaagccag actccagcat 5340
cagcagtcag gagcactaag cccttgccaa catcctgttt ctcagagaaa ctgcttccat 5400
tataatggtt gtcctttttt aagctatcaa gccaaacaac cagtgtctac cattattctc 5460
atcacctgaa gccaagggtt ctagcaaaag tcaagctgtc ttgtaatggt tgatgtgcct 5520
ccagcttctg tcttcagtca ctccactctt agcctgctct gaatcaactc tgaccacagt 5580
tccctggagc ccctgccacc tgctgcccct gccaccttct ccatctgcag tgctgtgcag 5640
ccttctgcac tcttgcagag ctaataggtg gagacttgaa ggaagaggag gaaagtttct 5700
cataatagcc ttgctgcaag ctcaaatggg aggtgggcac tgtgcccagg agccttggag 5760
caaaggctgt gcccaacctc tgactgcatc caggtttggt cttgacagag ataagaagcc 5820
ctggcttttg gagccaaaat ctaggtcaga cttaggcagg attctcaaag tttatcagca 5880
gaacatgagg cagaagaccc tttctgctcc agcttcttca ggctcaacct tcatcagaat 5940
agatagaaag agaggctgtg agggttctta aaacagaagc aaatctgact cagagaataa 6000
acaacctcct agtaaactac agcttagaca gagcatctgg tggtgagtgt gctcagtgtc 6060
ctactcaact gtctggtatc agccctcatg aggacttctc ttctttccct catagacctc 6120
catctctgtt ttccttagcc tgcagaaatc tggatggcta ttcacagaat gcctgtgctt 6180
tcagagttgc attttttctc tggtattctg gttcaagcat ttgaaggtag gaaaggttct 6240
ccaagtgcaa gaaagccagc cctgagcctc aactgcctgg ctagtgtggt cagtaggatg 6300
caaaggctgt tgaatgccac aaggccaaac tttaacctgt gtaccacaag cctagcagca 6360
gaggcagctc tgctcactgg aactctctgt cttctttctc ctgagccttt tcttttcctg 6420
agttttctag ctctcctcaa ccttacctct gccctaccca ggacaaaccc aagagccact 6480
gtttctgtga tgtcctctcc agccctaatt aggcatcatg acttcagcct gaccttccat 6540
gctcagaagc agtgctaatc cacttcagat gagctgctct atgcaacaca ggcagagcct 6600
acaaaccttt gcaccagagc cctccacata tcagtgtttg ttcatactca cttcaacagc 6660
aaatgtgact gctgagatta agattttaca caagatggtc tgtaatttca cagttagttt 6720
tatcccatta ggtatgaaag aattagcata attcccctta aacatgaatg aatcttagat 6780
tttttaataa atagttttgg aagtaaagac agagacatca ggagcacaag gaatagcctg 6840
agaggacaaa cagaacaaga aagagtctgg aaatacacag gatgttcttg gcctcctcaa 6900
agcaagtgca agcagatagt accagcagcc ccaggctatc agagcccagt gaagagaagt 6960
accatgaaag ccacagctct aaccaccctg ttccagagtg acagacagtc cccaagacaa 7020
gccagcctga gccagagaga gaactgcaag agaaagtttc taatttaggt tctgttagat 7080
tcagacaagt gcaggtcatc ctctctccac agctactcac ctctccagcc taacaaagcc 7140
tgcagtccac actccaaccc tggtgtctca cctcctagcc tctcccaaca tcctgctctc 7200
tgaccatctt ctgcatctct catctcacca tctcccactg tctacagcct actcttgcaa 7260
ctaccatctc attttctgac atcctgtcta catcttctgc catactctgc catctaccat 7320
accacctctt accatctacc acaccatctt ttatctccat ccctctcaga agcctccaag 7380
ctgaatcctg ctttatgtgt tcatctcagc ccctgcatgg aaagctgacc ccagaggcag 7440
aactattccc agagagcttg gccaagaaaa acaaaactac cagcctggcc aggctcagga 7500
gtagtaagct gcagtgtctg ttgtgttcta gcttcaacag ctgcaggagt tccactctca 7560
aatgctccac atttctcaca tcctcctgat tctggtcact acccatcttc aaagaacaga 7620
atatctcaca tcagcatact gtgaaggact agtcatgggt gcagctgctc agagctgcaa 7680
agtcattctg gatggtggag agcttacaaa catttcatga tgctcccccc gctctgatgg 7740
ctggagccca atccctacac agactcctgc tgtatgtgtt ttcctttcac tctgagccac 7800
agccagaggg caggcattca gtctcctctt caggctgggg ctggggcact gagaactcac 7860
ccaacacctt gctctcactc cttctgcaaa acaagaaaga gctttgtgct gcagtagcca 7920
tgaagaatga aaggaaggct ttaactaaaa aatgtcagag attattttca accccttact 7980
gtggatcacc agcaaggagg aaacacaaca cagagacatt ttttcccctc aaattatcaa 8040
aagaatcact gcatttgtta aagagagcaa ctgaatcagg aagcagagtt ttgaacatat 8100
cagaagttag gaatctgcat cagagacaaa tgcagtcatg gttgtttgct gcataccagc 8160
cctaatcatt agaagcctca tggacttcaa acatcattcc ctctgacaag atgctctagc 8220
ctaactccat gagataaaat aaatctgcct ttcagagcca aagaagagtc caccagcttc 8280
ttctcagtgt gaacaagagc tccagtcagg ttagtcagtc cagtgcagta gaggagacca 8340
gtctgcatcc tctaattttc aaaggcaaga agatttgttt accctggaca ccaggcacaa 8400
gtgaggtcac agagctctta gatatgcagt cctcatgagt gaggagacta aagcgcatgc 8460
catcaagact tcagtgtaga gaaaacctcc aaaaaagcct cctcactact tctggaatag 8520
ctcagaggcc gaggcggcct cggcctctgc ataaataaaa aaaattagtc agccatgggg 8580
cggagaatgg gcggaactgg gcggagttag gggcgggatg ggcggagtta ggggcgggac 8640
tatggttgct gactaattga gatgcatgct ttgcatactt ctgcctgctg gggagcctgg 8700
ggactttcca cacctggttg ctgactaatt gagatgcatg ctttgcatac ttctgcctgc 8760
tggggagcct ggggactttc cacaccctaa ctgacacaca ttccacagct gcattaatga 8820
atcggccaac gcgcggggag aggcggtttg cgtattgggc gctcttccgc ttcctcgctc 8880
actgactcgc tgcgctcggt cgttcggctg cggcgagcgg tatcagctca ctcaaaggcg 8940
gtaatacggt tatccacaga atcaggggat aacgcaggaa agaacatgtg agcaaaaggc 9000
cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg cgtttttcca taggctccgc 9060
ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga ggtggcgaaa cccgacagga 9120
ctataaagat accaggcgtt tccccctgga agctccctcg tgcgctctcc tgttccgacc 9180
ctgccgctta ccggatacct gtccgccttt ctcccttcgg gaagcgtggc gctttctcat 9240
agctcacgct gtaggtatct cagttcggtg taggtcgttc gctccaagct gggctgtgtg 9300
cacgaacccc ccgttcagcc cgaccgctgc gccttatccg gtaactatcg tcttgagtcc 9360
aacccggtaa gacacgactt atcgccactg gcagcagcca ctggtaacag gattagcaga 9420
gcgaggtatg taggcggtgc tacagagttc ttgaagtggt ggcctaacta cggctacact 9480
agaagaacag tatttggtat ctgcgctctg ctgaagccag ttaccttcgg aaaaagagtt 9540
ggtagctctt gatccggcaa acaaaccacc gctggtagcg gtggtttttt tgtttgcaag 9600
cagcagatta cgcgcagaaa aaaaggatct caagaagatc ctttgatctt ttctacgggg 9660
tctgacgctc agtggaacga aaactcacgt taagggattt tggtcatgag attatcaaaa 9720
aggatcttca cctagatcct tttaaattaa aaatgaagtt ttaaatcaat ctaaagtata 9780
tatgagtaaa cttggtctga cagttaccaa tgcttaatca gtgaggcacc tatctcagcg 9840
atctgtctat ttcgttcatc catagttgcc tgactcctgc aaaccacgtt gtgtctcaaa 9900
atctctgatg ttacattgca caagataaaa atatatcatc atgaacaata aaactgtctg 9960
cttacataaa cagtaataca aggggtgtta tgagccatat tcaacgggaa acgtcttgct 10020
cgaggccgcg attaaattcc aacatggatg ctgatttata tgggtataaa tgggctcgcg 10080
ataatgtcgg gcaatcaggt gcgacaatct atcgattgta tgggaagccc gatgcgccag 10140
agttgtttct gaaacatggc aaaggtagcg ttgccaatga tgttacagat gagatggtca 10200
gactaaactg gctgacggaa tttatgcctc ttccgaccat caagcatttt atccgtactc 10260
ctgatgatgc atggttactc accactgcga tccccgggaa aacagcattc caggtattag 10320
aagaatatcc tgattcaggt gaaaatattg ttgatgcgct ggcagtgttc ctgcgccggt 10380
tgcattcgat tcctgtttgt aattgtcctt ttaacagcga tcgcgtattt cgtctcgctc 10440
aggcgcaatc acgaatgaat aacggtttgg ttgatgcgag tgattttgat gacgagcgta 10500
atggctggcc tgttgaacaa gtctggaaag aaatgcataa gcttttgcca ttctcaccgg 10560
attcagtcgt cactcatggt gatttctcac ttgataacct tatttttgac gaggggaaat 10620
taataggttg tattgatgtt ggacgagtcg gaatcgcaga ccgataccag gatcttgcca 10680
tcctatggaa ctgcctcggt gagttttctc cttcattaca gaaacggctt tttcaaaaat 10740
atggtattga taatcctgat atgaataaat tgcagtttca tttgatgctc gatgagtttt 10800
tctaagggcg gcctgccacc atacccacgc cgaaacaagc gctcatgagc ccgaagtggc 10860
gagcccgatc ttccccatcg gtgatgtcgg cgatataggc gccagcaacc gcacctgtgg 10920
cgccggtgat gagggcgcgc caagtcgacg tccggcagtc 10960
<210> 24
<211> 10013
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 24
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctccgg gctgtaatta 1080
gcgcttggtt taatgacggc ttgttttctg tggctgcgtg aaagccttga ggggctccgg 1140
gagctagagc ctctgctaac catgttcatg ccttcttctt tttcctacag ctcctgggca 1200
acgtgctggt tattgtgctg tctcatcatt ttggcaaaga attcctcgaa gatccgaagg 1260
gaaagtcttc cacgactgtg ggatccgttc gaagatatca ccggttgagc caccatggac 1320
gtgttcatga agggcctgag caaggccaag gagggcgtgg tggccgccgc cgagaagacc 1380
aagcagggcg tggccgaggc cgccggcaag accaaggagg gcgtgctgta cgtgggcagc 1440
aagaccaagg agggcgtggt gcacggcgtg gccaccgtgg ccgagaagac caaggagcag 1500
gtgaccaacg tgggcggcgc cgtggtgacc ggcgtgaccg ccgtggccca gaagaccgtg 1560
gagggcgccg gcagcatcgc cgccgccacc ggcttcgtga agaaggacca gctgggcaag 1620
aacgaggagg gcgcccccca ggagggcatc ctggaggaca tgcccgtgga ccccgacaac 1680
gaggcctacg agatgcccag cgaggagggc taccaggact acgagcccga ggcctaagaa 1740
atatctttgc tcccagtttc ttgagatctg ctgacagatg ttccatcctg tacaagtgct 1800
cagttccaat gtgcccagtc atgacatttc tcaaagtttt tacagtgtat ctcgaagtct 1860
tccatcagca gtgattgaag tatctgtacc tgcccccact cagcatttcg gtgcttccct 1920
ttcactgaag tgaatacatg gtagcagggt ctttgtgtgc tgtggatttt gtggcttcaa 1980
tctacgatgt taaaacaaat taaaaacacc taagtgacta ccacttattt ctaaatcctc 2040
actatttttt tgttgctgtt gttcagaagt tgttagtgat ttgctatcat atattataag 2100
atttttaggt gtcttttaat gatactgtct aagaataatg acgtattgtg aaatttgtta 2160
atatatataa tacttaaaaa tatgtgagca tgaaactatg cacctataaa tactaaatat 2220
gaaattttac cattttgctg acaattgtta attaagttta aaccctcgag gccgcaagct 2280
tatcgataat caacctctgg attacaaaat ttgtgaaaga ttgactggta ttcttaacta 2340
tgttgctcct tttacgctat gtggatacgc tgctttaatg cctttgtatc atgctattgc 2400
ttcccgtatg gctttcattt tctcctcctt gtataaatcc tggttgctgt ctctttatga 2460
ggagttgtgg cccgttgtca ggcaacgtgg cgtggtgtgc actgtgtttg ctgacgcaac 2520
ccccactggt tggggcattg ccaccacctg tcagctcctt tccgggactt tcgctttccc 2580
cctccctatt gccacggcgg aactcatcgc cgcctgcctt gcccgctgct ggacaggggc 2640
tcggctgttg ggcactgaca attccgtggt gttgtcgggg aaatcatcgt cctttccttg 2700
gctgctcgcc tgtgttgcca cctggattct gcgcgggacg tccttctgct acgtcccttc 2760
ggccctcaat ccagcggacc ttccttcccg cggcctgctg ccggctctgc ggcctcttcc 2820
gcgtcttcgc cttcgccctc agacgagtcg gatctccctt tgggccgcct ccccgcatcg 2880
ataccgtcga ctagagctcg ctgatcagcc tcgactgtgc cttctagttg ccagccatct 2940
gttgtttgcc cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt 3000
tcctaataaa atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg 3060
ggtggggtgg ggcaggacag caagggggag gattgggaag acaatagcag gcatgctggg 3120
gagagatcca cgataacaaa cagctttttt ggggtgaaca tattgactga attccctgca 3180
ggttggccac tccctctctg cgcgctcgct cgctcactga ggccgcccgg gcaaagcccg 3240
ggcgtcgggc gacctttggt cgcccggcct cagtgagcga gcgagcgcgc agagagggag 3300
tggccaactc catcactagg ggttcctgcg gccgctcgta cggtctcgag gaattcctgc 3360
aggataactt gccaacctca ttctaaaatg tatatagaag cccaaaagac aataacaaaa 3420
atattcttgt agaacaaaat gggaaagaat gttccactaa atatcaagat ttagagcaaa 3480
gcatgagatg tgtggggata gacagtgagg ctgataaaat agagtagagc tcagaaacag 3540
acccattgat atatgtaagt gacctatgaa aaaaatatgg cattttacaa tgggaaaatg 3600
atggtctttt tcttttttag aaaaacaggg aaatatattt atatgtaaaa aataaaaggg 3660
aacccatatg tcataccata cacacaaaaa aattccagtg aattataagt ctaaatggag 3720
aaggcaaaac tttaaatctt ttagaaaata atatagaagc atgcagacca gcctggccaa 3780
catgatgaaa ccctctctac taataataaa atcagtagaa ctactcagga ctactttgag 3840
tgggaagtcc ttttctatga agacttcttt ggccaaaatt aggctctaaa tgcaaggaga 3900
tagtgcatca tgcctggctg cacttactga taaatgatgt tatcaccatc tttaaccaaa 3960
tgcacaggaa caagttatgg tactgatgtg ctggattgag aaggagctct acttccttga 4020
caggacacat ttgtatcaac ttaaaaaagc agatttttgc cagcagaact attcattcag 4080
aggtaggaaa cttagaatag atgatgtcac tgattagcat ggcttcccca tctccacagc 4140
tgcttcccac ccaggttgcc cacagttgag tttgtccagt gctcagggct gcccactctc 4200
agtaagaagc cccacaccag cccctctcca aatatgttgg ctgttccttc cattaaagtg 4260
accccacttt agagcagcaa gtggatttct gtttcttaca gttcaggaag gaggagtcag 4320
ctgtgagaac ctggagcctg agatgcttct aagtcccact gctactgggg tcagggaagc 4380
cagactccag catcagcagt caggagcact aagcccttgc caacatcctg tttctcagag 4440
aaactgcttc cattataatg gttgtccttt tttaagctat caagccaaac aaccagtgtc 4500
taccattatt ctcatcacct gaagccaagg gttctagcaa aagtcaagct gtcttgtaat 4560
ggttgatgtg cctccagctt ctgtcttcag tcactccact cttagcctgc tctgaatcaa 4620
ctctgaccac agttccctgg agcccctgcc acctgctgcc cctgccacct tctccatctg 4680
cagtgctgtg cagccttctg cactcttgca gagctaatag gtggagactt gaaggaagag 4740
gaggaaagtt tctcataata gccttgctgc aagctcaaat gggaggtggg cactgtgccc 4800
aggagccttg gagcaaaggc tgtgcccaac ctctgactgc atccaggttt ggtcttgaca 4860
gagataagaa gccctggctt ttggagccaa aatctaggtc agacttaggc aggattctca 4920
aagtttatca gcagaacatg aggcagaaga ccctttctgc tccagcttct tcaggctcaa 4980
ccttcatcag aatagataga aagagaggct gtgagggttc ttaaaacaga agcaaatctg 5040
actcagagaa taaacaacct cctagtaaac tacagcttag acagagcatc tggtggtgag 5100
tgtgctcagt gtcctactca actgtctggt atcagccctc atgaggactt ctcttctttc 5160
cctcatagac ctccatctct gttttcctta gcctgcagaa atctggatgg ctattcacag 5220
aatgcctgtg ctttcagagt tgcatttttt ctctggtatt ctggttcaag catttgaagg 5280
taggaaaggt tctccaagtg caagaaagcc agccctgagc ctcaactgcc tggctagtgt 5340
ggtcagtagg atgcaaaggc tgttgaatgc cacaaggcca aactttaacc tgtgtaccac 5400
aagcctagca gcagaggcag ctctgctcac tggaactctc tgtcttcttt ctcctgagcc 5460
ttttcttttc ctgagttttc tagctctcct caaccttacc tctgccctac ccaggacaaa 5520
cccaagagcc actgtttctg tgatgtcctc tccagcccta attaggcatc atgacttcag 5580
cctgaccttc catgctcaga agcagtgcta atccacttca gatgagctgc tctatgcaac 5640
acaggcagag cctacaaacc tttgcaccag agccctccac atatcagtgt ttgttcatac 5700
tcacttcaac agcaaatgtg actgctgaga ttaagatttt acacaagatg gtctgtaatt 5760
tcacagttag ttttatccca ttaggtatga aagaattagc ataattcccc ttaaacatga 5820
atgaatctta gattttttaa taaatagttt tggaagtaaa gacagagaca tcaggagcac 5880
aaggaatagc ctgagaggac aaacagaaca agaaagagtc tggaaataca caggatgttc 5940
ttggcctcct caaagcaagt gcaagcagat agtaccagca gccccaggct atcagagccc 6000
agtgaagaga agtaccatga aagccacagc tctaaccacc ctgttccaga gtgacagaca 6060
gtccccaaga caagccagcc tgagccagag agagaactgc aagagaaagt ttctaattta 6120
ggttctgtta gattcagaca agtgcaggtc atcctctctc cacagctact cacctctcca 6180
gcctaacaaa gcctgcagtc cacactccaa ccctggtgtc tcacctccta gcctctccca 6240
acatcctgct ctctgaccat cttctgcatc tctcatctca ccatctccca ctgtctacag 6300
cctactcttg caactaccat ctcattttct gacatcctgt ctacatcttc tgccatactc 6360
tgccatctac cataccacct cttaccatct accacaccat cttttatctc catccctctc 6420
agaagcctcc aagctgaatc ctgctttatg tgttcatctc agcccctgca tggaaagctg 6480
accccagagg cagaactatt cccagagagc ttggccaaga aaaacaaaac taccagcctg 6540
gccaggctca ggagtagtaa gctgcagtgt ctgttgtgtt ctagcttcaa cagctgcagg 6600
agttccactc tcaaatgctc cacatttctc acatcctcct gattctggtc actacccatc 6660
ttcaaagaac agaatatctc acatcagcat actgtgaagg actagtcatg ggtgcagctg 6720
ctcagagctg caaagtcatt ctggatggtg gagagcttac aaacatttca tgatgctccc 6780
cccgctctga tggctggagc ccaatcccta cacagactcc tgctgtatgt gttttccttt 6840
cactctgagc cacagccaga gggcaggcat tcagtctcct cttcaggctg gggctggggc 6900
actgagaact cacccaacac cttgctctca ctccttctgc aaaacaagaa agagctttgt 6960
gctgcagtag ccatgaagaa tgaaaggaag gctttaacta aaaaatgtca gagattattt 7020
tcaacccctt actgtggatc accagcaagg aggaaacaca acacagagac attttttccc 7080
ctcaaattat caaaagaatc actgcatttg ttaaagagag caactgaatc aggaagcaga 7140
gttttgaaca tatcagaagt taggaatctg catcagagac aaatgcagtc atggttgttt 7200
gctgcatacc agccctaatc attagaagcc tcatggactt caaacatcat tccctctgac 7260
aagatgctct agcctaactc catgagataa aataaatctg cctttcagag ccaaagaaga 7320
gtccaccagc ttcttctcag tgtgaacaag agctccagtc aggttagtca gtccagtgca 7380
gtagaggaga ccagtctgca tcctctaatt ttcaaaggca agaagatttg tttaccctgg 7440
acaccaggca caagtgaggt cacagagctc ttagatatgc agtcctcatg agtgaggaga 7500
ctaaagcgca tgccatcaag acttcagtgt agagaaaacc tccaaaaaag cctcctcact 7560
acttctggaa tagctcagag gccgaggcgg cctcggcctc tgcataaata aaaaaaatta 7620
gtcagccatg gggcggagaa tgggcggaac tgggcggagt taggggcggg atgggcggag 7680
ttaggggcgg gactatggtt gctgactaat tgagatgcat gctttgcata cttctgcctg 7740
ctggggagcc tggggacttt ccacacctgg ttgctgacta attgagatgc atgctttgca 7800
tacttctgcc tgctggggag cctggggact ttccacaccc taactgacac acattccaca 7860
gctgcattaa tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgctcttc 7920
cgcttcctcg ctcactgact cgctgcgctc ggtcgttcgg ctgcggcgag cggtatcagc 7980
tcactcaaag gcggtaatac ggttatccac agaatcaggg gataacgcag gaaagaacat 8040
gtgagcaaaa ggccagcaaa aggccaggaa ccgtaaaaag gccgcgttgc tggcgttttt 8100
ccataggctc cgcccccctg acgagcatca caaaaatcga cgctcaagtc agaggtggcg 8160
aaacccgaca ggactataaa gataccaggc gtttccccct ggaagctccc tcgtgcgctc 8220
tcctgttccg accctgccgc ttaccggata cctgtccgcc tttctccctt cgggaagcgt 8280
ggcgctttct catagctcac gctgtaggta tctcagttcg gtgtaggtcg ttcgctccaa 8340
gctgggctgt gtgcacgaac cccccgttca gcccgaccgc tgcgccttat ccggtaacta 8400
tcgtcttgag tccaacccgg taagacacga cttatcgcca ctggcagcag ccactggtaa 8460
caggattagc agagcgaggt atgtaggcgg tgctacagag ttcttgaagt ggtggcctaa 8520
ctacggctac actagaagaa cagtatttgg tatctgcgct ctgctgaagc cagttacctt 8580
cggaaaaaga gttggtagct cttgatccgg caaacaaacc accgctggta gcggtggttt 8640
ttttgtttgc aagcagcaga ttacgcgcag aaaaaaagga tctcaagaag atcctttgat 8700
cttttctacg gggtctgacg ctcagtggaa cgaaaactca cgttaaggga ttttggtcat 8760
gagattatca aaaaggatct tcacctagat ccttttaaat taaaaatgaa gttttaaatc 8820
aatctaaagt atatatgagt aaacttggtc tgacagttac caatgcttaa tcagtgaggc 8880
acctatctca gcgatctgtc tatttcgttc atccatagtt gcctgactcc tgcaaaccac 8940
gttgtgtctc aaaatctctg atgttacatt gcacaagata aaaatatatc atcatgaaca 9000
ataaaactgt ctgcttacat aaacagtaat acaaggggtg ttatgagcca tattcaacgg 9060
gaaacgtctt gctcgaggcc gcgattaaat tccaacatgg atgctgattt atatgggtat 9120
aaatgggctc gcgataatgt cgggcaatca ggtgcgacaa tctatcgatt gtatgggaag 9180
cccgatgcgc cagagttgtt tctgaaacat ggcaaaggta gcgttgccaa tgatgttaca 9240
gatgagatgg tcagactaaa ctggctgacg gaatttatgc ctcttccgac catcaagcat 9300
tttatccgta ctcctgatga tgcatggtta ctcaccactg cgatccccgg gaaaacagca 9360
ttccaggtat tagaagaata tcctgattca ggtgaaaata ttgttgatgc gctggcagtg 9420
ttcctgcgcc ggttgcattc gattcctgtt tgtaattgtc cttttaacag cgatcgcgta 9480
tttcgtctcg ctcaggcgca atcacgaatg aataacggtt tggttgatgc gagtgatttt 9540
gatgacgagc gtaatggctg gcctgttgaa caagtctgga aagaaatgca taagcttttg 9600
ccattctcac cggattcagt cgtcactcat ggtgatttct cacttgataa ccttattttt 9660
gacgagggga aattaatagg ttgtattgat gttggacgag tcggaatcgc agaccgatac 9720
caggatcttg ccatcctatg gaactgcctc ggtgagtttt ctccttcatt acagaaacgg 9780
ctttttcaaa aatatggtat tgataatcct gatatgaata aattgcagtt tcatttgatg 9840
ctcgatgagt ttttctaagg gcggcctgcc accataccca cgccgaaaca agcgctcatg 9900
agcccgaagt ggcgagcccg atcttcccca tcggtgatgt cggcgatata ggcgccagca 9960
accgcacctg tggcgccggt gatgagggcg cgccaagtcg acgtccggca gtc 10013
<210> 25
<211> 10849
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 25
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctccgg gctgtaatta 1080
gcgcttggtt taatgacggc ttgtctggag gcttgctttg ggctgtatgc tgtggaagac 1140
ttcgagatac actgtttttg gcctctgact gaacagtgtt ctgaagtctt ccacaggaca 1200
caaggccctt tatcagcact cacatggaac aaatggccac cgtgggagga tgacaatttc 1260
tgtggctgcg tgaaagcctt gaggggctcc gggagctaga gcctctgcta accatgttca 1320
tgccttcttc tttttcctac agctcctggg caacgtgctg gttattgtgc tgtctcatca 1380
ttttggcaaa gaattcctcg aagatccgaa gggaaagtct tccacgactg tgggatccgt 1440
tcgaagatat caccggttga gccaccatgg aattcagcag ccccagcaga gaggaatgcc 1500
ccaagcctct gagccgggtg tcaatcatgg ccggatctct gacaggactg ctgctgcttc 1560
aggccgtgtc ttgggcttct ggcgctagac cttgcatccc caagagcttc ggctacagca 1620
gcgtcgtgtg cgtgtgcaat gccacctact gcgacagctt cgaccctcct acctttcctg 1680
ctctgggcac cttcagcaga tacgagagca ccagatccgg cagacggatg gaactgagca 1740
tgggacccat ccaggccaat cacacaggca ctggcctgct gctgacactg cagcctgagc 1800
agaaattcca gaaagtgaaa ggcttcggcg gagccatgac agatgccgcc gctctgaata 1860
tcctggctct gtctccacca gctcagaacc tgctgctcaa gagctacttc agcgaggaag 1920
gcatcggcta caacatcatc agagtgccca tggccagctg cgacttcagc atcaggacct 1980
acacctacgc cgacacaccc gacgatttcc agctgcacaa cttcagcctg cctgaagagg 2040
acaccaagct gaagatccct ctgatccaca gagccctgca gctggcacaa agacccgtgt 2100
cactgctggc ctctccatgg acatctccca cctggctgaa aacaaatggc gccgtgaatg 2160
gcaagggcag cctgaaaggc caacctggcg acatctacca ccagacctgg gccagatact 2220
tcgtgaagtt cctggacgcc tatgccgagc acaagctgca gttttgggcc gtgacagccg 2280
agaacgaacc ttctgctgga ctgctgagcg gctacccctt tcagtgcctg ggctttacac 2340
ccgagcacca gcgggacttt atcgcccgtg atctgggacc cacactggcc aatagcaccc 2400
accataatgt gcggctgctg atgctggacg accagagact gcttctgccc cactgggcta 2460
aagtggtgct gacagatcct gaggccgcca aatacgtgca cggaatcgcc gtgcactggt 2520
atctggactt tctggcccct gccaaggcca cactgggaga gacacacaga ctgttcccca 2580
acaccatgct gttcgccagc gaagcctgtg tgggcagcaa gttttgggaa cagagcgtgc 2640
ggctcggcag ctgggataga ggcatgcagt acagccacag catcatcacc aacctgctgt 2700
accacgtcgt cggctggacc gactggaatc tggccctgaa tcctgaaggc ggccctaact 2760
gggtccgaaa cttcgtggac agccccatca tcgtggacat caccaaggac accttctaca 2820
agcagcccat gttctaccac ctgggacact tcagcaagtt catccccgag ggctctcagc 2880
gcgttggact ggtggcttcc cagaagaacg atctggacgc cgtggctctg atgcaccctg 2940
atggatctgc tgtggtggtg gtcctgaacc gcagcagcaa agatgtgccc ctgaccatca 3000
aggatcccgc cgtgggattc ctggaaacaa tcagccctgg ctactccatc cacacctacc 3060
tgtggcgtag acagtgacaa ttgttaatta agtttaaacc ctcgaggccg caagcttatc 3120
gataatcaac ctctggatta caaaatttgt gaaagattga ctggtattct taactatgtt 3180
gctcctttta cgctatgtgg atacgctgct ttaatgcctt tgtatcatgc tattgcttcc 3240
cgtatggctt tcattttctc ctccttgtat aaatcctggt tgctgtctct ttatgaggag 3300
ttgtggcccg ttgtcaggca acgtggcgtg gtgtgcactg tgtttgctga cgcaaccccc 3360
actggttggg gcattgccac cacctgtcag ctcctttccg ggactttcgc tttccccctc 3420
cctattgcca cggcggaact catcgccgcc tgccttgccc gctgctggac aggggctcgg 3480
ctgttgggca ctgacaattc cgtggtgttg tcggggaaat catcgtcctt tccttggctg 3540
ctcgcctgtg ttgccacctg gattctgcgc gggacgtcct tctgctacgt cccttcggcc 3600
ctcaatccag cggaccttcc ttcccgcggc ctgctgccgg ctctgcggcc tcttccgcgt 3660
cttcgccttc gccctcagac gagtcggatc tccctttggg ccgcctcccc gcatcgatac 3720
cgtcgactag agctcgctga tcagcctcga ctgtgccttc tagttgccag ccatctgttg 3780
tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc cactcccact gtcctttcct 3840
aataaaatga ggaaattgca tcgcattgtc tgagtaggtg tcattctatt ctggggggtg 3900
gggtggggca ggacagcaag ggggaggatt gggaagacaa tagcaggcat gctggggaga 3960
gatccacgat aacaaacagc ttttttgggg tgaacatatt gactgaattc cctgcaggtt 4020
ggccactccc tctctgcgcg ctcgctcgct cactgaggcc gcccgggcaa agcccgggcg 4080
tcgggcgacc tttggtcgcc cggcctcagt gagcgagcga gcgcgcagag agggagtggc 4140
caactccatc actaggggtt cctgcggccg ctcgtacggt ctcgaggaat tcctgcagga 4200
taacttgcca acctcattct aaaatgtata tagaagccca aaagacaata acaaaaatat 4260
tcttgtagaa caaaatggga aagaatgttc cactaaatat caagatttag agcaaagcat 4320
gagatgtgtg gggatagaca gtgaggctga taaaatagag tagagctcag aaacagaccc 4380
attgatatat gtaagtgacc tatgaaaaaa atatggcatt ttacaatggg aaaatgatgg 4440
tctttttctt ttttagaaaa acagggaaat atatttatat gtaaaaaata aaagggaacc 4500
catatgtcat accatacaca caaaaaaatt ccagtgaatt ataagtctaa atggagaagg 4560
caaaacttta aatcttttag aaaataatat agaagcatgc agaccagcct ggccaacatg 4620
atgaaaccct ctctactaat aataaaatca gtagaactac tcaggactac tttgagtggg 4680
aagtcctttt ctatgaagac ttctttggcc aaaattaggc tctaaatgca aggagatagt 4740
gcatcatgcc tggctgcact tactgataaa tgatgttatc accatcttta accaaatgca 4800
caggaacaag ttatggtact gatgtgctgg attgagaagg agctctactt ccttgacagg 4860
acacatttgt atcaacttaa aaaagcagat ttttgccagc agaactattc attcagaggt 4920
aggaaactta gaatagatga tgtcactgat tagcatggct tccccatctc cacagctgct 4980
tcccacccag gttgcccaca gttgagtttg tccagtgctc agggctgccc actctcagta 5040
agaagcccca caccagcccc tctccaaata tgttggctgt tccttccatt aaagtgaccc 5100
cactttagag cagcaagtgg atttctgttt cttacagttc aggaaggagg agtcagctgt 5160
gagaacctgg agcctgagat gcttctaagt cccactgcta ctggggtcag ggaagccaga 5220
ctccagcatc agcagtcagg agcactaagc ccttgccaac atcctgtttc tcagagaaac 5280
tgcttccatt ataatggttg tcctttttta agctatcaag ccaaacaacc agtgtctacc 5340
attattctca tcacctgaag ccaagggttc tagcaaaagt caagctgtct tgtaatggtt 5400
gatgtgcctc cagcttctgt cttcagtcac tccactctta gcctgctctg aatcaactct 5460
gaccacagtt ccctggagcc cctgccacct gctgcccctg ccaccttctc catctgcagt 5520
gctgtgcagc cttctgcact cttgcagagc taataggtgg agacttgaag gaagaggagg 5580
aaagtttctc ataatagcct tgctgcaagc tcaaatggga ggtgggcact gtgcccagga 5640
gccttggagc aaaggctgtg cccaacctct gactgcatcc aggtttggtc ttgacagaga 5700
taagaagccc tggcttttgg agccaaaatc taggtcagac ttaggcagga ttctcaaagt 5760
ttatcagcag aacatgaggc agaagaccct ttctgctcca gcttcttcag gctcaacctt 5820
catcagaata gatagaaaga gaggctgtga gggttcttaa aacagaagca aatctgactc 5880
agagaataaa caacctccta gtaaactaca gcttagacag agcatctggt ggtgagtgtg 5940
ctcagtgtcc tactcaactg tctggtatca gccctcatga ggacttctct tctttccctc 6000
atagacctcc atctctgttt tccttagcct gcagaaatct ggatggctat tcacagaatg 6060
cctgtgcttt cagagttgca ttttttctct ggtattctgg ttcaagcatt tgaaggtagg 6120
aaaggttctc caagtgcaag aaagccagcc ctgagcctca actgcctggc tagtgtggtc 6180
agtaggatgc aaaggctgtt gaatgccaca aggccaaact ttaacctgtg taccacaagc 6240
ctagcagcag aggcagctct gctcactgga actctctgtc ttctttctcc tgagcctttt 6300
cttttcctga gttttctagc tctcctcaac cttacctctg ccctacccag gacaaaccca 6360
agagccactg tttctgtgat gtcctctcca gccctaatta ggcatcatga cttcagcctg 6420
accttccatg ctcagaagca gtgctaatcc acttcagatg agctgctcta tgcaacacag 6480
gcagagccta caaacctttg caccagagcc ctccacatat cagtgtttgt tcatactcac 6540
ttcaacagca aatgtgactg ctgagattaa gattttacac aagatggtct gtaatttcac 6600
agttagtttt atcccattag gtatgaaaga attagcataa ttccccttaa acatgaatga 6660
atcttagatt ttttaataaa tagttttgga agtaaagaca gagacatcag gagcacaagg 6720
aatagcctga gaggacaaac agaacaagaa agagtctgga aatacacagg atgttcttgg 6780
cctcctcaaa gcaagtgcaa gcagatagta ccagcagccc caggctatca gagcccagtg 6840
aagagaagta ccatgaaagc cacagctcta accaccctgt tccagagtga cagacagtcc 6900
ccaagacaag ccagcctgag ccagagagag aactgcaaga gaaagtttct aatttaggtt 6960
ctgttagatt cagacaagtg caggtcatcc tctctccaca gctactcacc tctccagcct 7020
aacaaagcct gcagtccaca ctccaaccct ggtgtctcac ctcctagcct ctcccaacat 7080
cctgctctct gaccatcttc tgcatctctc atctcaccat ctcccactgt ctacagccta 7140
ctcttgcaac taccatctca ttttctgaca tcctgtctac atcttctgcc atactctgcc 7200
atctaccata ccacctctta ccatctacca caccatcttt tatctccatc cctctcagaa 7260
gcctccaagc tgaatcctgc tttatgtgtt catctcagcc cctgcatgga aagctgaccc 7320
cagaggcaga actattccca gagagcttgg ccaagaaaaa caaaactacc agcctggcca 7380
ggctcaggag tagtaagctg cagtgtctgt tgtgttctag cttcaacagc tgcaggagtt 7440
ccactctcaa atgctccaca tttctcacat cctcctgatt ctggtcacta cccatcttca 7500
aagaacagaa tatctcacat cagcatactg tgaaggacta gtcatgggtg cagctgctca 7560
gagctgcaaa gtcattctgg atggtggaga gcttacaaac atttcatgat gctccccccg 7620
ctctgatggc tggagcccaa tccctacaca gactcctgct gtatgtgttt tcctttcact 7680
ctgagccaca gccagagggc aggcattcag tctcctcttc aggctggggc tggggcactg 7740
agaactcacc caacaccttg ctctcactcc ttctgcaaaa caagaaagag ctttgtgctg 7800
cagtagccat gaagaatgaa aggaaggctt taactaaaaa atgtcagaga ttattttcaa 7860
ccccttactg tggatcacca gcaaggagga aacacaacac agagacattt tttcccctca 7920
aattatcaaa agaatcactg catttgttaa agagagcaac tgaatcagga agcagagttt 7980
tgaacatatc agaagttagg aatctgcatc agagacaaat gcagtcatgg ttgtttgctg 8040
cataccagcc ctaatcatta gaagcctcat ggacttcaaa catcattccc tctgacaaga 8100
tgctctagcc taactccatg agataaaata aatctgcctt tcagagccaa agaagagtcc 8160
accagcttct tctcagtgtg aacaagagct ccagtcaggt tagtcagtcc agtgcagtag 8220
aggagaccag tctgcatcct ctaattttca aaggcaagaa gatttgttta ccctggacac 8280
caggcacaag tgaggtcaca gagctcttag atatgcagtc ctcatgagtg aggagactaa 8340
agcgcatgcc atcaagactt cagtgtagag aaaacctcca aaaaagcctc ctcactactt 8400
ctggaatagc tcagaggccg aggcggcctc ggcctctgca taaataaaaa aaattagtca 8460
gccatggggc ggagaatggg cggaactggg cggagttagg ggcgggatgg gcggagttag 8520
gggcgggact atggttgctg actaattgag atgcatgctt tgcatacttc tgcctgctgg 8580
ggagcctggg gactttccac acctggttgc tgactaattg agatgcatgc tttgcatact 8640
tctgcctgct ggggagcctg gggactttcc acaccctaac tgacacacat tccacagctg 8700
cattaatgaa tcggccaacg cgcggggaga ggcggtttgc gtattgggcg ctcttccgct 8760
tcctcgctca ctgactcgct gcgctcggtc gttcggctgc ggcgagcggt atcagctcac 8820
tcaaaggcgg taatacggtt atccacagaa tcaggggata acgcaggaaa gaacatgtga 8880
gcaaaaggcc agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc gtttttccat 8940
aggctccgcc cccctgacga gcatcacaaa aatcgacgct caagtcagag gtggcgaaac 9000
ccgacaggac tataaagata ccaggcgttt ccccctggaa gctccctcgt gcgctctcct 9060
gttccgaccc tgccgcttac cggatacctg tccgcctttc tcccttcggg aagcgtggcg 9120
ctttctcata gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg 9180
ggctgtgtgc acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt 9240
cttgagtcca acccggtaag acacgactta tcgccactgg cagcagccac tggtaacagg 9300
attagcagag cgaggtatgt aggcggtgct acagagttct tgaagtggtg gcctaactac 9360
ggctacacta gaagaacagt atttggtatc tgcgctctgc tgaagccagt taccttcgga 9420
aaaagagttg gtagctcttg atccggcaaa caaaccaccg ctggtagcgg tggttttttt 9480
gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt 9540
tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt ggtcatgaga 9600
ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt taaatcaatc 9660
taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag tgaggcacct 9720
atctcagcga tctgtctatt tcgttcatcc atagttgcct gactcctgca aaccacgttg 9780
tgtctcaaaa tctctgatgt tacattgcac aagataaaaa tatatcatca tgaacaataa 9840
aactgtctgc ttacataaac agtaatacaa ggggtgttat gagccatatt caacgggaaa 9900
cgtcttgctc gaggccgcga ttaaattcca acatggatgc tgatttatat gggtataaat 9960
gggctcgcga taatgtcggg caatcaggtg cgacaatcta tcgattgtat gggaagcccg 10020
atgcgccaga gttgtttctg aaacatggca aaggtagcgt tgccaatgat gttacagatg 10080
agatggtcag actaaactgg ctgacggaat ttatgcctct tccgaccatc aagcatttta 10140
tccgtactcc tgatgatgca tggttactca ccactgcgat ccccgggaaa acagcattcc 10200
aggtattaga agaatatcct gattcaggtg aaaatattgt tgatgcgctg gcagtgttcc 10260
tgcgccggtt gcattcgatt cctgtttgta attgtccttt taacagcgat cgcgtatttc 10320
gtctcgctca ggcgcaatca cgaatgaata acggtttggt tgatgcgagt gattttgatg 10380
acgagcgtaa tggctggcct gttgaacaag tctggaaaga aatgcataag cttttgccat 10440
tctcaccgga ttcagtcgtc actcatggtg atttctcact tgataacctt atttttgacg 10500
aggggaaatt aataggttgt attgatgttg gacgagtcgg aatcgcagac cgataccagg 10560
atcttgccat cctatggaac tgcctcggtg agttttctcc ttcattacag aaacggcttt 10620
ttcaaaaata tggtattgat aatcctgata tgaataaatt gcagtttcat ttgatgctcg 10680
atgagttttt ctaagggcgg cctgccacca tacccacgcc gaaacaagcg ctcatgagcc 10740
cgaagtggcg agcccgatct tccccatcgg tgatgtcggc gatataggcg ccagcaaccg 10800
cacctgtggc gccggtgatg agggcgcgcc aagtcgacgt ccggcagtc 10849
<210> 26
<211> 11231
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 26
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctagtaacag gccttgtgtc 300
cttttagaaa taagtggtag tcacatctgt ggcttcactt gactaccact tatttctaaa 360
gacaacagca tacagccttc agcaagcctc cagtggtctc atacagaact tataagattc 420
ccaaatccaa agacatttca cgtttatggt gatttcccag aacacatagc gacatgcaaa 480
tattgcaggg cgccactccc ctgtccctca cagccatctt cctgccaggg cgcacgcgcg 540
ctgggtgttc ccgcctagtg acactgggcc cgcgattcct tggagcgggt tgatgacgtc 600
agcgtttccc atggtgaagc ttggatctga tccctaggtt ctagaaccgg tgacattcgg 660
taccctagtt attaatagta atcaattacg gggtcattag ttcatagccc atatatggag 720
ttccgcgtta cataacttac ggtaaatggc ccgcctggct gaccgcccaa cgacccccgc 780
ccattgacgt caataatgac gtatgttccc atagtaacgc caatagggac tttccattga 840
cgtcaatggg tggactattt acggtaaact gcccacttgg cagtacatca agtgtatcat 900
atgccaagta cgccccctat tgacgtcaat gacggtaaat ggcccgcctg gcattatgcc 960
cagtacatga ccttatggga ctttcctact tggcagtaca tctacgtatt agtcatcgct 1020
attaccatgg tcgaggtgag ccccacgttc tgcttcactc tccccatctc ccccccctcc 1080
ccacccccaa ttttgtattt atttattttt taattatttt gtgcagcgat gggggcgggg 1140
gggggggggg ggcgcgcgcc aggcggggcg gggcggggcg aggggcgggg cggggcgagg 1200
cggagaggtg cggcggcagc caatcagagc ggcgcgctcc gaaagtttcc ttttatggcg 1260
aggcggcggc ggcggcggcc ctataaaaag cgaagcgcgc ggcgggcggg agtcgctgcg 1320
acgctgcctt cgccccgtgc cccgctccgc cgccgcctcg cgccgcccgc cccggctctg 1380
actgaccgcg ttactcccac aggtgagcgg gcgggacggc ccttctcctc cgggctgtaa 1440
ttagcgcttg gtttaatgac ggcttgtttt ctgtggctgc gtgaaagcct tgaggggctc 1500
cgggagctag agcctctgct aaccatgttc atgccttctt ctttttccta cagctcctgg 1560
gcaacgtgct ggttattgtg ctgtctcatc attttggcaa agaattcctc gaagatccga 1620
agggaaagtc ttccacgact gtgggatccg ttcgaagata tcaccggttg agccaccatg 1680
tggaccctgg tgagctgggt ggccctgacc gccggcctgg tggccggcac ccgctgcccc 1740
gacggccagt tctgccccgt ggcctgctgc ctggaccccg gcggcgccag ctacagctgc 1800
tgccgccccc tgctggacaa gtggcccacc accctgagcc gccacctggg cggcccctgc 1860
caggtggacg cccactgcag cgccggccac agctgcatct tcaccgtgag cggcaccagc 1920
agctgctgcc ccttccccga ggccgtggcc tgcggcgacg gccaccactg ctgcccccgc 1980
ggcttccact gcagcgccga cggccgcagc tgcttccagc gcagcggcaa caacagcgtg 2040
ggcgccatcc agtgccccga cagccagttc gagtgccccg acttcagcac ctgctgcgtg 2100
atggtggacg gcagctgggg ctgctgcccc atgccccagg ccagctgctg cgaggaccgc 2160
gtgcactgct gcccccacgg cgccttctgc gacctggtgc acacccgctg catcaccccc 2220
accggcaccc accccctggc caagaagctg cccgcccagc gcaccaaccg cgccgtggcc 2280
ctgagcagca gcgtgatgtg ccccgacgcc cgcagccgct gccccgacgg cagcacctgc 2340
tgcgagctgc ccagcggcaa gtacggctgc tgccccatgc ccaacgccac ctgctgcagc 2400
gaccacctgc actgctgccc ccaggacacc gtgtgcgacc tgatccagag caagtgcctg 2460
agcaaggaga acgccaccac cgacctgctg accaagctgc ccgcccacac cgtgggcgac 2520
gtgaagtgcg acatggaggt gagctgcccc gacggctaca cctgctgccg cctgcagagc 2580
ggcgcctggg gctgctgccc cttcacccag gccgtgtgct gcgaggacca catccactgc 2640
tgccccgccg gcttcacctg cgacacccag aagggcacct gcgagcaggg cccccaccag 2700
gtgccctgga tggagaaggc ccccgcccac ctgagcctgc ccgaccccca ggccctgaag 2760
cgcgacgtgc cctgcgacaa cgtgagcagc tgccccagca gcgacacctg ctgccagctg 2820
accagcggcg agtggggctg ctgccccatc cccgaggccg tgtgctgcag cgaccaccag 2880
cactgctgcc cccagggcta cacctgcgtg gccgagggcc agtgccagcg cggcagcgag 2940
atcgtggccg gcctggagaa gatgcccgcc cgccgcgcca gcctgagcca cccccgcgac 3000
atcggctgcg accagcacac cagctgcccc gtgggccaga cctgctgccc cagcctgggc 3060
ggcagctggg cctgctgcca gctgccccac gccgtgtgct gcgaggaccg ccagcactgc 3120
tgccccgccg gctacacctg caacgtgaag gcccgcagct gcgagaagga ggtggtgagc 3180
gcccagcccg ccaccttcct ggcccgcagc ccccacgtgg gcgtgaagga cgtggagtgc 3240
ggcgagggcc acttctgcca cgacaaccag acctgctgcc gcgacaaccg ccagggctgg 3300
gcctgctgcc cctaccgcca gggcgtgtgc tgcgccgacc gccgccactg ctgccccgcc 3360
ggcttccgct gcgccgcccg cggcaccaag tgcctgcgcc gcgaggcccc ccgctgggac 3420
gcccccctgc gcgaccccgc cctgcgccag ctgctgtgac aattgttaat taagtttaaa 3480
ccctcgaggc cgcaagctta tcgataatca acctctggat tacaaaattt gtgaaagatt 3540
gactggtatt cttaactatg ttgctccttt tacgctatgt ggatacgctg ctttaatgcc 3600
tttgtatcat gctattgctt cccgtatggc tttcattttc tcctccttgt ataaatcctg 3660
gttgctgtct ctttatgagg agttgtggcc cgttgtcagg caacgtggcg tggtgtgcac 3720
tgtgtttgct gacgcaaccc ccactggttg gggcattgcc accacctgtc agctcctttc 3780
cgggactttc gctttccccc tccctattgc cacggcggaa ctcatcgccg cctgccttgc 3840
ccgctgctgg acaggggctc ggctgttggg cactgacaat tccgtggtgt tgtcggggaa 3900
atcatcgtcc tttccttggc tgctcgcctg tgttgccacc tggattctgc gcgggacgtc 3960
cttctgctac gtcccttcgg ccctcaatcc agcggacctt ccttcccgcg gcctgctgcc 4020
ggctctgcgg cctcttccgc gtcttcgcct tcgccctcag acgagtcgga tctccctttg 4080
ggccgcctcc ccgcatcgat accgtcgact agagctcgct gatcagcctc gactgtgcct 4140
tctagttgcc agccatctgt tgtttgcccc tcccccgtgc cttccttgac cctggaaggt 4200
gccactccca ctgtcctttc ctaataaaat gaggaaattg catcgcattg tctgagtagg 4260
tgtcattcta ttctgggggg tggggtgggg caggacagca agggggagga ttgggaagac 4320
aatagcaggc atgctgggga gagatccacg ataacaaaca gcttttttgg ggtgaacata 4380
ttgactgaat tccctgcagg ttggccactc cctctctgcg cgctcgctcg ctcactgagg 4440
ccgcccgggc aaagcccggg cgtcgggcga cctttggtcg cccggcctca gtgagcgagc 4500
gagcgcgcag agagggagtg gccaactcca tcactagggg ttcctgcggc cgctcgtacg 4560
gtctcgagga attcctgcag gataacttgc caacctcatt ctaaaatgta tatagaagcc 4620
caaaagacaa taacaaaaat attcttgtag aacaaaatgg gaaagaatgt tccactaaat 4680
atcaagattt agagcaaagc atgagatgtg tggggataga cagtgaggct gataaaatag 4740
agtagagctc agaaacagac ccattgatat atgtaagtga cctatgaaaa aaatatggca 4800
ttttacaatg ggaaaatgat ggtctttttc ttttttagaa aaacagggaa atatatttat 4860
atgtaaaaaa taaaagggaa cccatatgtc ataccataca cacaaaaaaa ttccagtgaa 4920
ttataagtct aaatggagaa ggcaaaactt taaatctttt agaaaataat atagaagcat 4980
gcagaccagc ctggccaaca tgatgaaacc ctctctacta ataataaaat cagtagaact 5040
actcaggact actttgagtg ggaagtcctt ttctatgaag acttctttgg ccaaaattag 5100
gctctaaatg caaggagata gtgcatcatg cctggctgca cttactgata aatgatgtta 5160
tcaccatctt taaccaaatg cacaggaaca agttatggta ctgatgtgct ggattgagaa 5220
ggagctctac ttccttgaca ggacacattt gtatcaactt aaaaaagcag atttttgcca 5280
gcagaactat tcattcagag gtaggaaact tagaatagat gatgtcactg attagcatgg 5340
cttccccatc tccacagctg cttcccaccc aggttgccca cagttgagtt tgtccagtgc 5400
tcagggctgc ccactctcag taagaagccc cacaccagcc cctctccaaa tatgttggct 5460
gttccttcca ttaaagtgac cccactttag agcagcaagt ggatttctgt ttcttacagt 5520
tcaggaagga ggagtcagct gtgagaacct ggagcctgag atgcttctaa gtcccactgc 5580
tactggggtc agggaagcca gactccagca tcagcagtca ggagcactaa gcccttgcca 5640
acatcctgtt tctcagagaa actgcttcca ttataatggt tgtccttttt taagctatca 5700
agccaaacaa ccagtgtcta ccattattct catcacctga agccaagggt tctagcaaaa 5760
gtcaagctgt cttgtaatgg ttgatgtgcc tccagcttct gtcttcagtc actccactct 5820
tagcctgctc tgaatcaact ctgaccacag ttccctggag cccctgccac ctgctgcccc 5880
tgccaccttc tccatctgca gtgctgtgca gccttctgca ctcttgcaga gctaataggt 5940
ggagacttga aggaagagga ggaaagtttc tcataatagc cttgctgcaa gctcaaatgg 6000
gaggtgggca ctgtgcccag gagccttgga gcaaaggctg tgcccaacct ctgactgcat 6060
ccaggtttgg tcttgacaga gataagaagc cctggctttt ggagccaaaa tctaggtcag 6120
acttaggcag gattctcaaa gtttatcagc agaacatgag gcagaagacc ctttctgctc 6180
cagcttcttc aggctcaacc ttcatcagaa tagatagaaa gagaggctgt gagggttctt 6240
aaaacagaag caaatctgac tcagagaata aacaacctcc tagtaaacta cagcttagac 6300
agagcatctg gtggtgagtg tgctcagtgt cctactcaac tgtctggtat cagccctcat 6360
gaggacttct cttctttccc tcatagacct ccatctctgt tttccttagc ctgcagaaat 6420
ctggatggct attcacagaa tgcctgtgct ttcagagttg cattttttct ctggtattct 6480
ggttcaagca tttgaaggta ggaaaggttc tccaagtgca agaaagccag ccctgagcct 6540
caactgcctg gctagtgtgg tcagtaggat gcaaaggctg ttgaatgcca caaggccaaa 6600
ctttaacctg tgtaccacaa gcctagcagc agaggcagct ctgctcactg gaactctctg 6660
tcttctttct cctgagcctt ttcttttcct gagttttcta gctctcctca accttacctc 6720
tgccctaccc aggacaaacc caagagccac tgtttctgtg atgtcctctc cagccctaat 6780
taggcatcat gacttcagcc tgaccttcca tgctcagaag cagtgctaat ccacttcaga 6840
tgagctgctc tatgcaacac aggcagagcc tacaaacctt tgcaccagag ccctccacat 6900
atcagtgttt gttcatactc acttcaacag caaatgtgac tgctgagatt aagattttac 6960
acaagatggt ctgtaatttc acagttagtt ttatcccatt aggtatgaaa gaattagcat 7020
aattcccctt aaacatgaat gaatcttaga ttttttaata aatagttttg gaagtaaaga 7080
cagagacatc aggagcacaa ggaatagcct gagaggacaa acagaacaag aaagagtctg 7140
gaaatacaca ggatgttctt ggcctcctca aagcaagtgc aagcagatag taccagcagc 7200
cccaggctat cagagcccag tgaagagaag taccatgaaa gccacagctc taaccaccct 7260
gttccagagt gacagacagt ccccaagaca agccagcctg agccagagag agaactgcaa 7320
gagaaagttt ctaatttagg ttctgttaga ttcagacaag tgcaggtcat cctctctcca 7380
cagctactca cctctccagc ctaacaaagc ctgcagtcca cactccaacc ctggtgtctc 7440
acctcctagc ctctcccaac atcctgctct ctgaccatct tctgcatctc tcatctcacc 7500
atctcccact gtctacagcc tactcttgca actaccatct cattttctga catcctgtct 7560
acatcttctg ccatactctg ccatctacca taccacctct taccatctac cacaccatct 7620
tttatctcca tccctctcag aagcctccaa gctgaatcct gctttatgtg ttcatctcag 7680
cccctgcatg gaaagctgac cccagaggca gaactattcc cagagagctt ggccaagaaa 7740
aacaaaacta ccagcctggc caggctcagg agtagtaagc tgcagtgtct gttgtgttct 7800
agcttcaaca gctgcaggag ttccactctc aaatgctcca catttctcac atcctcctga 7860
ttctggtcac tacccatctt caaagaacag aatatctcac atcagcatac tgtgaaggac 7920
tagtcatggg tgcagctgct cagagctgca aagtcattct ggatggtgga gagcttacaa 7980
acatttcatg atgctccccc cgctctgatg gctggagccc aatccctaca cagactcctg 8040
ctgtatgtgt tttcctttca ctctgagcca cagccagagg gcaggcattc agtctcctct 8100
tcaggctggg gctggggcac tgagaactca cccaacacct tgctctcact ccttctgcaa 8160
aacaagaaag agctttgtgc tgcagtagcc atgaagaatg aaaggaaggc tttaactaaa 8220
aaatgtcaga gattattttc aaccccttac tgtggatcac cagcaaggag gaaacacaac 8280
acagagacat tttttcccct caaattatca aaagaatcac tgcatttgtt aaagagagca 8340
actgaatcag gaagcagagt tttgaacata tcagaagtta ggaatctgca tcagagacaa 8400
atgcagtcat ggttgtttgc tgcataccag ccctaatcat tagaagcctc atggacttca 8460
aacatcattc cctctgacaa gatgctctag cctaactcca tgagataaaa taaatctgcc 8520
tttcagagcc aaagaagagt ccaccagctt cttctcagtg tgaacaagag ctccagtcag 8580
gttagtcagt ccagtgcagt agaggagacc agtctgcatc ctctaatttt caaaggcaag 8640
aagatttgtt taccctggac accaggcaca agtgaggtca cagagctctt agatatgcag 8700
tcctcatgag tgaggagact aaagcgcatg ccatcaagac ttcagtgtag agaaaacctc 8760
caaaaaagcc tcctcactac ttctggaata gctcagaggc cgaggcggcc tcggcctctg 8820
cataaataaa aaaaattagt cagccatggg gcggagaatg ggcggaactg ggcggagtta 8880
ggggcgggat gggcggagtt aggggcggga ctatggttgc tgactaattg agatgcatgc 8940
tttgcatact tctgcctgct ggggagcctg gggactttcc acacctggtt gctgactaat 9000
tgagatgcat gctttgcata cttctgcctg ctggggagcc tggggacttt ccacacccta 9060
actgacacac attccacagc tgcattaatg aatcggccaa cgcgcgggga gaggcggttt 9120
gcgtattggg cgctcttccg cttcctcgct cactgactcg ctgcgctcgg tcgttcggct 9180
gcggcgagcg gtatcagctc actcaaaggc ggtaatacgg ttatccacag aatcagggga 9240
taacgcagga aagaacatgt gagcaaaagg ccagcaaaag gccaggaacc gtaaaaaggc 9300
cgcgttgctg gcgtttttcc ataggctccg cccccctgac gagcatcaca aaaatcgacg 9360
ctcaagtcag aggtggcgaa acccgacagg actataaaga taccaggcgt ttccccctgg 9420
aagctccctc gtgcgctctc ctgttccgac cctgccgctt accggatacc tgtccgcctt 9480
tctcccttcg ggaagcgtgg cgctttctca tagctcacgc tgtaggtatc tcagttcggt 9540
gtaggtcgtt cgctccaagc tgggctgtgt gcacgaaccc cccgttcagc ccgaccgctg 9600
cgccttatcc ggtaactatc gtcttgagtc caacccggta agacacgact tatcgccact 9660
ggcagcagcc actggtaaca ggattagcag agcgaggtat gtaggcggtg ctacagagtt 9720
cttgaagtgg tggcctaact acggctacac tagaagaaca gtatttggta tctgcgctct 9780
gctgaagcca gttaccttcg gaaaaagagt tggtagctct tgatccggca aacaaaccac 9840
cgctggtagc ggtggttttt ttgtttgcaa gcagcagatt acgcgcagaa aaaaaggatc 9900
tcaagaagat cctttgatct tttctacggg gtctgacgct cagtggaacg aaaactcacg 9960
ttaagggatt ttggtcatga gattatcaaa aaggatcttc acctagatcc ttttaaatta 10020
aaaatgaagt tttaaatcaa tctaaagtat atatgagtaa acttggtctg acagttacca 10080
atgcttaatc agtgaggcac ctatctcagc gatctgtcta tttcgttcat ccatagttgc 10140
ctgactcctg caaaccacgt tgtgtctcaa aatctctgat gttacattgc acaagataaa 10200
aatatatcat catgaacaat aaaactgtct gcttacataa acagtaatac aaggggtgtt 10260
atgagccata ttcaacggga aacgtcttgc tcgaggccgc gattaaattc caacatggat 10320
gctgatttat atgggtataa atgggctcgc gataatgtcg ggcaatcagg tgcgacaatc 10380
tatcgattgt atgggaagcc cgatgcgcca gagttgtttc tgaaacatgg caaaggtagc 10440
gttgccaatg atgttacaga tgagatggtc agactaaact ggctgacgga atttatgcct 10500
cttccgacca tcaagcattt tatccgtact cctgatgatg catggttact caccactgcg 10560
atccccggga aaacagcatt ccaggtatta gaagaatatc ctgattcagg tgaaaatatt 10620
gttgatgcgc tggcagtgtt cctgcgccgg ttgcattcga ttcctgtttg taattgtcct 10680
tttaacagcg atcgcgtatt tcgtctcgct caggcgcaat cacgaatgaa taacggtttg 10740
gttgatgcga gtgattttga tgacgagcgt aatggctggc ctgttgaaca agtctggaaa 10800
gaaatgcata agcttttgcc attctcaccg gattcagtcg tcactcatgg tgatttctca 10860
cttgataacc ttatttttga cgaggggaaa ttaataggtt gtattgatgt tggacgagtc 10920
ggaatcgcag accgatacca ggatcttgcc atcctatgga actgcctcgg tgagttttct 10980
ccttcattac agaaacggct ttttcaaaaa tatggtattg ataatcctga tatgaataaa 11040
ttgcagtttc atttgatgct cgatgagttt ttctaagggc ggcctgccac catacccacg 11100
ccgaaacaag cgctcatgag cccgaagtgg cgagcccgat cttccccatc ggtgatgtcg 11160
gcgatatagg cgccagcaac cgcacctgtg gcgccggtga tgagggcgcg ccaagtcgac 11220
gtccggcagt c 11231
<210> 27
<211> 10876
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 27
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctcagc gctgtaatta 1080
gcgcttggtt taatgacggc ttgttggagg cttgctgaag gctgtatgct gttgtcctcg 1140
agtgagcgta gggtatcaag actacgaata ctgtaaagcc acagatgggt gttcgtagtc 1200
ttgataccct tcgcctacta gaggacacaa ggcctgttac tagcactcac atggaacaaa 1260
tggccaccgt gggaggatga caatttctgt ggctgcgtga aagccttgag gggctccggg 1320
agctagagcc tctgctaacc atgttcatgc cttcttcttt ttcctacagc tcctgggcaa 1380
cgtgctggtt attgtgctgt ctcatcattt tggcaaagaa ttcctcgaag atccgaaggg 1440
aaagtcttcc acgactgtgg gatccgttcg aagatatcac cggttgagcc accatggaat 1500
tcagcagccc cagcagagag gaatgcccca agcctctgag ccgggtgtca atcatggccg 1560
gatctctgac aggactgctg ctgcttcagg ccgtgtcttg ggcttctggc gctagacctt 1620
gcatccccaa gagcttcggc tacagcagcg tcgtgtgcgt gtgcaatgcc acctactgcg 1680
acagcttcga ccctcctacc tttcctgctc tgggcacctt cagcagatac gagagcacca 1740
gatccggcag acggatggaa ctgagcatgg gacccatcca ggccaatcac acaggcactg 1800
gcctgctgct gacactgcag cctgagcaga aattccagaa agtgaaaggc ttcggcggag 1860
ccatgacaga tgccgccgct ctgaatatcc tggctctgtc tccaccagct cagaacctgc 1920
tgctcaagag ctacttcagc gaggaaggca tcggctacaa catcatcaga gtgcccatgg 1980
ccagctgcga cttcagcatc aggacctaca cctacgccga cacacccgac gatttccagc 2040
tgcacaactt cagcctgcct gaagaggaca ccaagctgaa gatccctctg atccacagag 2100
ccctgcagct ggcacaaaga cccgtgtcac tgctggcctc tccatggaca tctcccacct 2160
ggctgaaaac aaatggcgcc gtgaatggca agggcagcct gaaaggccaa cctggcgaca 2220
tctaccacca gacctgggcc agatacttcg tgaagttcct ggacgcctat gccgagcaca 2280
agctgcagtt ttgggccgtg acagccgaga acgaaccttc tgctggactg ctgagcggct 2340
acccctttca gtgcctgggc tttacacccg agcaccagcg ggactttatc gcccgtgatc 2400
tgggacccac actggccaat agcacccacc ataatgtgcg gctgctgatg ctggacgacc 2460
agagactgct tctgccccac tgggctaaag tggtgctgac agatcctgag gccgccaaat 2520
acgtgcacgg aatcgccgtg cactggtatc tggactttct ggcccctgcc aaggccacac 2580
tgggagagac acacagactg ttccccaaca ccatgctgtt cgccagcgaa gcctgtgtgg 2640
gcagcaagtt ttgggaacag agcgtgcggc tcggcagctg ggatagaggc atgcagtaca 2700
gccacagcat catcaccaac ctgctgtacc acgtcgtcgg ctggaccgac tggaatctgg 2760
ccctgaatcc tgaaggcggc cctaactggg tccgaaactt cgtggacagc cccatcatcg 2820
tggacatcac caaggacacc ttctacaagc agcccatgtt ctaccacctg ggacacttca 2880
gcaagttcat ccccgagggc tctcagcgcg ttggactggt ggcttcccag aagaacgatc 2940
tggacgccgt ggctctgatg caccctgatg gatctgctgt ggtggtggtc ctgaaccgca 3000
gcagcaaaga tgtgcccctg accatcaagg atcccgccgt gggattcctg gaaacaatca 3060
gccctggcta ctccatccac acctacctgt ggcgtagaca gtgacaattg ttaattaagt 3120
ttaaaccctc gaggccgcaa gcttatcgat aatcaacctc tggattacaa aatttgtgaa 3180
agattgactg gtattcttaa ctatgttgct ccttttacgc tatgtggata cgctgcttta 3240
atgcctttgt atcatgctat tgcttcccgt atggctttca ttttctcctc cttgtataaa 3300
tcctggttgc tgtctcttta tgaggagttg tggcccgttg tcaggcaacg tggcgtggtg 3360
tgcactgtgt ttgctgacgc aacccccact ggttggggca ttgccaccac ctgtcagctc 3420
ctttccggga ctttcgcttt ccccctccct attgccacgg cggaactcat cgccgcctgc 3480
cttgcccgct gctggacagg ggctcggctg ttgggcactg acaattccgt ggtgttgtcg 3540
gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg ccacctggat tctgcgcggg 3600
acgtccttct gctacgtccc ttcggccctc aatccagcgg accttccttc ccgcggcctg 3660
ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc ctcagacgag tcggatctcc 3720
ctttgggccg cctccccgca tcgataccgt cgactagagc tcgctgatca gcctcgactg 3780
tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg 3840
aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga 3900
gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg 3960
aagacaatag caggcatgct ggggagagat ccacgataac aaacagcttt tttggggtga 4020
acatattgac tgaattccct gcaggttggc cactccctct ctgcgcgctc gctcgctcac 4080
tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt ggtcgcccgg cctcagtgag 4140
cgagcgagcg cgcagagagg gagtggccaa ctccatcact aggggttcct gcggccgctc 4200
gtacggtctc gaggaattcc tgcaggataa cttgccaacc tcattctaaa atgtatatag 4260
aagcccaaaa gacaataaca aaaatattct tgtagaacaa aatgggaaag aatgttccac 4320
taaatatcaa gatttagagc aaagcatgag atgtgtgggg atagacagtg aggctgataa 4380
aatagagtag agctcagaaa cagacccatt gatatatgta agtgacctat gaaaaaaata 4440
tggcatttta caatgggaaa atgatggtct ttttcttttt tagaaaaaca gggaaatata 4500
tttatatgta aaaaataaaa gggaacccat atgtcatacc atacacacaa aaaaattcca 4560
gtgaattata agtctaaatg gagaaggcaa aactttaaat cttttagaaa ataatataga 4620
agcatgcaga ccagcctggc caacatgatg aaaccctctc tactaataat aaaatcagta 4680
gaactactca ggactacttt gagtgggaag tccttttcta tgaagacttc tttggccaaa 4740
attaggctct aaatgcaagg agatagtgca tcatgcctgg ctgcacttac tgataaatga 4800
tgttatcacc atctttaacc aaatgcacag gaacaagtta tggtactgat gtgctggatt 4860
gagaaggagc tctacttcct tgacaggaca catttgtatc aacttaaaaa agcagatttt 4920
tgccagcaga actattcatt cagaggtagg aaacttagaa tagatgatgt cactgattag 4980
catggcttcc ccatctccac agctgcttcc cacccaggtt gcccacagtt gagtttgtcc 5040
agtgctcagg gctgcccact ctcagtaaga agccccacac cagcccctct ccaaatatgt 5100
tggctgttcc ttccattaaa gtgaccccac tttagagcag caagtggatt tctgtttctt 5160
acagttcagg aaggaggagt cagctgtgag aacctggagc ctgagatgct tctaagtccc 5220
actgctactg gggtcaggga agccagactc cagcatcagc agtcaggagc actaagccct 5280
tgccaacatc ctgtttctca gagaaactgc ttccattata atggttgtcc ttttttaagc 5340
tatcaagcca aacaaccagt gtctaccatt attctcatca cctgaagcca agggttctag 5400
caaaagtcaa gctgtcttgt aatggttgat gtgcctccag cttctgtctt cagtcactcc 5460
actcttagcc tgctctgaat caactctgac cacagttccc tggagcccct gccacctgct 5520
gcccctgcca ccttctccat ctgcagtgct gtgcagcctt ctgcactctt gcagagctaa 5580
taggtggaga cttgaaggaa gaggaggaaa gtttctcata atagccttgc tgcaagctca 5640
aatgggaggt gggcactgtg cccaggagcc ttggagcaaa ggctgtgccc aacctctgac 5700
tgcatccagg tttggtcttg acagagataa gaagccctgg cttttggagc caaaatctag 5760
gtcagactta ggcaggattc tcaaagttta tcagcagaac atgaggcaga agaccctttc 5820
tgctccagct tcttcaggct caaccttcat cagaatagat agaaagagag gctgtgaggg 5880
ttcttaaaac agaagcaaat ctgactcaga gaataaacaa cctcctagta aactacagct 5940
tagacagagc atctggtggt gagtgtgctc agtgtcctac tcaactgtct ggtatcagcc 6000
ctcatgagga cttctcttct ttccctcata gacctccatc tctgttttcc ttagcctgca 6060
gaaatctgga tggctattca cagaatgcct gtgctttcag agttgcattt tttctctggt 6120
attctggttc aagcatttga aggtaggaaa ggttctccaa gtgcaagaaa gccagccctg 6180
agcctcaact gcctggctag tgtggtcagt aggatgcaaa ggctgttgaa tgccacaagg 6240
ccaaacttta acctgtgtac cacaagccta gcagcagagg cagctctgct cactggaact 6300
ctctgtcttc tttctcctga gccttttctt ttcctgagtt ttctagctct cctcaacctt 6360
acctctgccc tacccaggac aaacccaaga gccactgttt ctgtgatgtc ctctccagcc 6420
ctaattaggc atcatgactt cagcctgacc ttccatgctc agaagcagtg ctaatccact 6480
tcagatgagc tgctctatgc aacacaggca gagcctacaa acctttgcac cagagccctc 6540
cacatatcag tgtttgttca tactcacttc aacagcaaat gtgactgctg agattaagat 6600
tttacacaag atggtctgta atttcacagt tagttttatc ccattaggta tgaaagaatt 6660
agcataattc cccttaaaca tgaatgaatc ttagattttt taataaatag ttttggaagt 6720
aaagacagag acatcaggag cacaaggaat agcctgagag gacaaacaga acaagaaaga 6780
gtctggaaat acacaggatg ttcttggcct cctcaaagca agtgcaagca gatagtacca 6840
gcagccccag gctatcagag cccagtgaag agaagtacca tgaaagccac agctctaacc 6900
accctgttcc agagtgacag acagtcccca agacaagcca gcctgagcca gagagagaac 6960
tgcaagagaa agtttctaat ttaggttctg ttagattcag acaagtgcag gtcatcctct 7020
ctccacagct actcacctct ccagcctaac aaagcctgca gtccacactc caaccctggt 7080
gtctcacctc ctagcctctc ccaacatcct gctctctgac catcttctgc atctctcatc 7140
tcaccatctc ccactgtcta cagcctactc ttgcaactac catctcattt tctgacatcc 7200
tgtctacatc ttctgccata ctctgccatc taccatacca cctcttacca tctaccacac 7260
catcttttat ctccatccct ctcagaagcc tccaagctga atcctgcttt atgtgttcat 7320
ctcagcccct gcatggaaag ctgaccccag aggcagaact attcccagag agcttggcca 7380
agaaaaacaa aactaccagc ctggccaggc tcaggagtag taagctgcag tgtctgttgt 7440
gttctagctt caacagctgc aggagttcca ctctcaaatg ctccacattt ctcacatcct 7500
cctgattctg gtcactaccc atcttcaaag aacagaatat ctcacatcag catactgtga 7560
aggactagtc atgggtgcag ctgctcagag ctgcaaagtc attctggatg gtggagagct 7620
tacaaacatt tcatgatgct ccccccgctc tgatggctgg agcccaatcc ctacacagac 7680
tcctgctgta tgtgttttcc tttcactctg agccacagcc agagggcagg cattcagtct 7740
cctcttcagg ctggggctgg ggcactgaga actcacccaa caccttgctc tcactccttc 7800
tgcaaaacaa gaaagagctt tgtgctgcag tagccatgaa gaatgaaagg aaggctttaa 7860
ctaaaaaatg tcagagatta ttttcaaccc cttactgtgg atcaccagca aggaggaaac 7920
acaacacaga gacatttttt cccctcaaat tatcaaaaga atcactgcat ttgttaaaga 7980
gagcaactga atcaggaagc agagttttga acatatcaga agttaggaat ctgcatcaga 8040
gacaaatgca gtcatggttg tttgctgcat accagcccta atcattagaa gcctcatgga 8100
cttcaaacat cattccctct gacaagatgc tctagcctaa ctccatgaga taaaataaat 8160
ctgcctttca gagccaaaga agagtccacc agcttcttct cagtgtgaac aagagctcca 8220
gtcaggttag tcagtccagt gcagtagagg agaccagtct gcatcctcta attttcaaag 8280
gcaagaagat ttgtttaccc tggacaccag gcacaagtga ggtcacagag ctcttagata 8340
tgcagtcctc atgagtgagg agactaaagc gcatgccatc aagacttcag tgtagagaaa 8400
acctccaaaa aagcctcctc actacttctg gaatagctca gaggccgagg cggcctcggc 8460
ctctgcataa ataaaaaaaa ttagtcagcc atggggcgga gaatgggcgg aactgggcgg 8520
agttaggggc gggatgggcg gagttagggg cgggactatg gttgctgact aattgagatg 8580
catgctttgc atacttctgc ctgctgggga gcctggggac tttccacacc tggttgctga 8640
ctaattgaga tgcatgcttt gcatacttct gcctgctggg gagcctgggg actttccaca 8700
ccctaactga cacacattcc acagctgcat taatgaatcg gccaacgcgc ggggagaggc 8760
ggtttgcgta ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg ctcggtcgtt 8820
cggctgcggc gagcggtatc agctcactca aaggcggtaa tacggttatc cacagaatca 8880
ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag gaaccgtaaa 8940
aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca tcacaaaaat 9000
cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca ggcgtttccc 9060
cctggaagct ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc 9120
gcctttctcc cttcgggaag cgtggcgctt tctcatagct cacgctgtag gtatctcagt 9180
tcggtgtagg tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt tcagcccgac 9240
cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc cggtaagaca cgacttatcg 9300
ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg cggtgctaca 9360
gagttcttga agtggtggcc taactacggc tacactagaa gaacagtatt tggtatctgc 9420
gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc cggcaaacaa 9480
accaccgctg gtagcggtgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa 9540
ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac 9600
tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta 9660
aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt 9720
taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg ttcatccata 9780
gttgcctgac tcctgcaaac cacgttgtgt ctcaaaatct ctgatgttac attgcacaag 9840
ataaaaatat atcatcatga acaataaaac tgtctgctta cataaacagt aatacaaggg 9900
gtgttatgag ccatattcaa cgggaaacgt cttgctcgag gccgcgatta aattccaaca 9960
tggatgctga tttatatggg tataaatggg ctcgcgataa tgtcgggcaa tcaggtgcga 10020
caatctatcg attgtatggg aagcccgatg cgccagagtt gtttctgaaa catggcaaag 10080
gtagcgttgc caatgatgtt acagatgaga tggtcagact aaactggctg acggaattta 10140
tgcctcttcc gaccatcaag cattttatcc gtactcctga tgatgcatgg ttactcacca 10200
ctgcgatccc cgggaaaaca gcattccagg tattagaaga atatcctgat tcaggtgaaa 10260
atattgttga tgcgctggca gtgttcctgc gccggttgca ttcgattcct gtttgtaatt 10320
gtccttttaa cagcgatcgc gtatttcgtc tcgctcaggc gcaatcacga atgaataacg 10380
gtttggttga tgcgagtgat tttgatgacg agcgtaatgg ctggcctgtt gaacaagtct 10440
ggaaagaaat gcataagctt ttgccattct caccggattc agtcgtcact catggtgatt 10500
tctcacttga taaccttatt tttgacgagg ggaaattaat aggttgtatt gatgttggac 10560
gagtcggaat cgcagaccga taccaggatc ttgccatcct atggaactgc ctcggtgagt 10620
tttctccttc attacagaaa cggctttttc aaaaatatgg tattgataat cctgatatga 10680
ataaattgca gtttcatttg atgctcgatg agtttttcta agggcggcct gccaccatac 10740
ccacgccgaa acaagcgctc atgagcccga agtggcgagc ccgatcttcc ccatcggtga 10800
tgtcggcgat ataggcgcca gcaaccgcac ctgtggcgcc ggtgatgagg gcgcgccaag 10860
tcgacgtccg gcagtc 10876
<210> 28
<211> 10849
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 28
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctcagc gctgtaatta 1080
gcgcttggtt taatgacggc ttgttggagg cttgctgaag gctgtatgct gttgtcttta 1140
gaaataagtg gtagtcaagt gaagccacag atgtgactac cacttatttc taaaaggaca 1200
caaggcctgt tactagcact cacatggaac aaatggccac cgtgggagga tgacaatttc 1260
tgtggctgcg tgaaagcctt gaggggctcc gggagctaga gcctctgcta accatgttca 1320
tgccttcttc tttttcctac agctcctggg caacgtgctg gttattgtgc tgtctcatca 1380
ttttggcaaa gaattcctcg aagatccgaa gggaaagtct tccacgactg tgggatccgt 1440
tcgaagatat caccggttga gccaccatgg aattcagcag ccccagcaga gaggaatgcc 1500
ccaagcctct gagccgggtg tcaatcatgg ccggatctct gacaggactg ctgctgcttc 1560
aggccgtgtc ttgggcttct ggcgctagac cttgcatccc caagagcttc ggctacagca 1620
gcgtcgtgtg cgtgtgcaat gccacctact gcgacagctt cgaccctcct acctttcctg 1680
ctctgggcac cttcagcaga tacgagagca ccagatccgg cagacggatg gaactgagca 1740
tgggacccat ccaggccaat cacacaggca ctggcctgct gctgacactg cagcctgagc 1800
agaaattcca gaaagtgaaa ggcttcggcg gagccatgac agatgccgcc gctctgaata 1860
tcctggctct gtctccacca gctcagaacc tgctgctcaa gagctacttc agcgaggaag 1920
gcatcggcta caacatcatc agagtgccca tggccagctg cgacttcagc atcaggacct 1980
acacctacgc cgacacaccc gacgatttcc agctgcacaa cttcagcctg cctgaagagg 2040
acaccaagct gaagatccct ctgatccaca gagccctgca gctggcacaa agacccgtgt 2100
cactgctggc ctctccatgg acatctccca cctggctgaa aacaaatggc gccgtgaatg 2160
gcaagggcag cctgaaaggc caacctggcg acatctacca ccagacctgg gccagatact 2220
tcgtgaagtt cctggacgcc tatgccgagc acaagctgca gttttgggcc gtgacagccg 2280
agaacgaacc ttctgctgga ctgctgagcg gctacccctt tcagtgcctg ggctttacac 2340
ccgagcacca gcgggacttt atcgcccgtg atctgggacc cacactggcc aatagcaccc 2400
accataatgt gcggctgctg atgctggacg accagagact gcttctgccc cactgggcta 2460
aagtggtgct gacagatcct gaggccgcca aatacgtgca cggaatcgcc gtgcactggt 2520
atctggactt tctggcccct gccaaggcca cactgggaga gacacacaga ctgttcccca 2580
acaccatgct gttcgccagc gaagcctgtg tgggcagcaa gttttgggaa cagagcgtgc 2640
ggctcggcag ctgggataga ggcatgcagt acagccacag catcatcacc aacctgctgt 2700
accacgtcgt cggctggacc gactggaatc tggccctgaa tcctgaaggc ggccctaact 2760
gggtccgaaa cttcgtggac agccccatca tcgtggacat caccaaggac accttctaca 2820
agcagcccat gttctaccac ctgggacact tcagcaagtt catccccgag ggctctcagc 2880
gcgttggact ggtggcttcc cagaagaacg atctggacgc cgtggctctg atgcaccctg 2940
atggatctgc tgtggtggtg gtcctgaacc gcagcagcaa agatgtgccc ctgaccatca 3000
aggatcccgc cgtgggattc ctggaaacaa tcagccctgg ctactccatc cacacctacc 3060
tgtggcgtag acagtgacaa ttgttaatta agtttaaacc ctcgaggccg caagcttatc 3120
gataatcaac ctctggatta caaaatttgt gaaagattga ctggtattct taactatgtt 3180
gctcctttta cgctatgtgg atacgctgct ttaatgcctt tgtatcatgc tattgcttcc 3240
cgtatggctt tcattttctc ctccttgtat aaatcctggt tgctgtctct ttatgaggag 3300
ttgtggcccg ttgtcaggca acgtggcgtg gtgtgcactg tgtttgctga cgcaaccccc 3360
actggttggg gcattgccac cacctgtcag ctcctttccg ggactttcgc tttccccctc 3420
cctattgcca cggcggaact catcgccgcc tgccttgccc gctgctggac aggggctcgg 3480
ctgttgggca ctgacaattc cgtggtgttg tcggggaaat catcgtcctt tccttggctg 3540
ctcgcctgtg ttgccacctg gattctgcgc gggacgtcct tctgctacgt cccttcggcc 3600
ctcaatccag cggaccttcc ttcccgcggc ctgctgccgg ctctgcggcc tcttccgcgt 3660
cttcgccttc gccctcagac gagtcggatc tccctttggg ccgcctcccc gcatcgatac 3720
cgtcgactag agctcgctga tcagcctcga ctgtgccttc tagttgccag ccatctgttg 3780
tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc cactcccact gtcctttcct 3840
aataaaatga ggaaattgca tcgcattgtc tgagtaggtg tcattctatt ctggggggtg 3900
gggtggggca ggacagcaag ggggaggatt gggaagacaa tagcaggcat gctggggaga 3960
gatccacgat aacaaacagc ttttttgggg tgaacatatt gactgaattc cctgcaggtt 4020
ggccactccc tctctgcgcg ctcgctcgct cactgaggcc gcccgggcaa agcccgggcg 4080
tcgggcgacc tttggtcgcc cggcctcagt gagcgagcga gcgcgcagag agggagtggc 4140
caactccatc actaggggtt cctgcggccg ctcgtacggt ctcgaggaat tcctgcagga 4200
taacttgcca acctcattct aaaatgtata tagaagccca aaagacaata acaaaaatat 4260
tcttgtagaa caaaatggga aagaatgttc cactaaatat caagatttag agcaaagcat 4320
gagatgtgtg gggatagaca gtgaggctga taaaatagag tagagctcag aaacagaccc 4380
attgatatat gtaagtgacc tatgaaaaaa atatggcatt ttacaatggg aaaatgatgg 4440
tctttttctt ttttagaaaa acagggaaat atatttatat gtaaaaaata aaagggaacc 4500
catatgtcat accatacaca caaaaaaatt ccagtgaatt ataagtctaa atggagaagg 4560
caaaacttta aatcttttag aaaataatat agaagcatgc agaccagcct ggccaacatg 4620
atgaaaccct ctctactaat aataaaatca gtagaactac tcaggactac tttgagtggg 4680
aagtcctttt ctatgaagac ttctttggcc aaaattaggc tctaaatgca aggagatagt 4740
gcatcatgcc tggctgcact tactgataaa tgatgttatc accatcttta accaaatgca 4800
caggaacaag ttatggtact gatgtgctgg attgagaagg agctctactt ccttgacagg 4860
acacatttgt atcaacttaa aaaagcagat ttttgccagc agaactattc attcagaggt 4920
aggaaactta gaatagatga tgtcactgat tagcatggct tccccatctc cacagctgct 4980
tcccacccag gttgcccaca gttgagtttg tccagtgctc agggctgccc actctcagta 5040
agaagcccca caccagcccc tctccaaata tgttggctgt tccttccatt aaagtgaccc 5100
cactttagag cagcaagtgg atttctgttt cttacagttc aggaaggagg agtcagctgt 5160
gagaacctgg agcctgagat gcttctaagt cccactgcta ctggggtcag ggaagccaga 5220
ctccagcatc agcagtcagg agcactaagc ccttgccaac atcctgtttc tcagagaaac 5280
tgcttccatt ataatggttg tcctttttta agctatcaag ccaaacaacc agtgtctacc 5340
attattctca tcacctgaag ccaagggttc tagcaaaagt caagctgtct tgtaatggtt 5400
gatgtgcctc cagcttctgt cttcagtcac tccactctta gcctgctctg aatcaactct 5460
gaccacagtt ccctggagcc cctgccacct gctgcccctg ccaccttctc catctgcagt 5520
gctgtgcagc cttctgcact cttgcagagc taataggtgg agacttgaag gaagaggagg 5580
aaagtttctc ataatagcct tgctgcaagc tcaaatggga ggtgggcact gtgcccagga 5640
gccttggagc aaaggctgtg cccaacctct gactgcatcc aggtttggtc ttgacagaga 5700
taagaagccc tggcttttgg agccaaaatc taggtcagac ttaggcagga ttctcaaagt 5760
ttatcagcag aacatgaggc agaagaccct ttctgctcca gcttcttcag gctcaacctt 5820
catcagaata gatagaaaga gaggctgtga gggttcttaa aacagaagca aatctgactc 5880
agagaataaa caacctccta gtaaactaca gcttagacag agcatctggt ggtgagtgtg 5940
ctcagtgtcc tactcaactg tctggtatca gccctcatga ggacttctct tctttccctc 6000
atagacctcc atctctgttt tccttagcct gcagaaatct ggatggctat tcacagaatg 6060
cctgtgcttt cagagttgca ttttttctct ggtattctgg ttcaagcatt tgaaggtagg 6120
aaaggttctc caagtgcaag aaagccagcc ctgagcctca actgcctggc tagtgtggtc 6180
agtaggatgc aaaggctgtt gaatgccaca aggccaaact ttaacctgtg taccacaagc 6240
ctagcagcag aggcagctct gctcactgga actctctgtc ttctttctcc tgagcctttt 6300
cttttcctga gttttctagc tctcctcaac cttacctctg ccctacccag gacaaaccca 6360
agagccactg tttctgtgat gtcctctcca gccctaatta ggcatcatga cttcagcctg 6420
accttccatg ctcagaagca gtgctaatcc acttcagatg agctgctcta tgcaacacag 6480
gcagagccta caaacctttg caccagagcc ctccacatat cagtgtttgt tcatactcac 6540
ttcaacagca aatgtgactg ctgagattaa gattttacac aagatggtct gtaatttcac 6600
agttagtttt atcccattag gtatgaaaga attagcataa ttccccttaa acatgaatga 6660
atcttagatt ttttaataaa tagttttgga agtaaagaca gagacatcag gagcacaagg 6720
aatagcctga gaggacaaac agaacaagaa agagtctgga aatacacagg atgttcttgg 6780
cctcctcaaa gcaagtgcaa gcagatagta ccagcagccc caggctatca gagcccagtg 6840
aagagaagta ccatgaaagc cacagctcta accaccctgt tccagagtga cagacagtcc 6900
ccaagacaag ccagcctgag ccagagagag aactgcaaga gaaagtttct aatttaggtt 6960
ctgttagatt cagacaagtg caggtcatcc tctctccaca gctactcacc tctccagcct 7020
aacaaagcct gcagtccaca ctccaaccct ggtgtctcac ctcctagcct ctcccaacat 7080
cctgctctct gaccatcttc tgcatctctc atctcaccat ctcccactgt ctacagccta 7140
ctcttgcaac taccatctca ttttctgaca tcctgtctac atcttctgcc atactctgcc 7200
atctaccata ccacctctta ccatctacca caccatcttt tatctccatc cctctcagaa 7260
gcctccaagc tgaatcctgc tttatgtgtt catctcagcc cctgcatgga aagctgaccc 7320
cagaggcaga actattccca gagagcttgg ccaagaaaaa caaaactacc agcctggcca 7380
ggctcaggag tagtaagctg cagtgtctgt tgtgttctag cttcaacagc tgcaggagtt 7440
ccactctcaa atgctccaca tttctcacat cctcctgatt ctggtcacta cccatcttca 7500
aagaacagaa tatctcacat cagcatactg tgaaggacta gtcatgggtg cagctgctca 7560
gagctgcaaa gtcattctgg atggtggaga gcttacaaac atttcatgat gctccccccg 7620
ctctgatggc tggagcccaa tccctacaca gactcctgct gtatgtgttt tcctttcact 7680
ctgagccaca gccagagggc aggcattcag tctcctcttc aggctggggc tggggcactg 7740
agaactcacc caacaccttg ctctcactcc ttctgcaaaa caagaaagag ctttgtgctg 7800
cagtagccat gaagaatgaa aggaaggctt taactaaaaa atgtcagaga ttattttcaa 7860
ccccttactg tggatcacca gcaaggagga aacacaacac agagacattt tttcccctca 7920
aattatcaaa agaatcactg catttgttaa agagagcaac tgaatcagga agcagagttt 7980
tgaacatatc agaagttagg aatctgcatc agagacaaat gcagtcatgg ttgtttgctg 8040
cataccagcc ctaatcatta gaagcctcat ggacttcaaa catcattccc tctgacaaga 8100
tgctctagcc taactccatg agataaaata aatctgcctt tcagagccaa agaagagtcc 8160
accagcttct tctcagtgtg aacaagagct ccagtcaggt tagtcagtcc agtgcagtag 8220
aggagaccag tctgcatcct ctaattttca aaggcaagaa gatttgttta ccctggacac 8280
caggcacaag tgaggtcaca gagctcttag atatgcagtc ctcatgagtg aggagactaa 8340
agcgcatgcc atcaagactt cagtgtagag aaaacctcca aaaaagcctc ctcactactt 8400
ctggaatagc tcagaggccg aggcggcctc ggcctctgca taaataaaaa aaattagtca 8460
gccatggggc ggagaatggg cggaactggg cggagttagg ggcgggatgg gcggagttag 8520
gggcgggact atggttgctg actaattgag atgcatgctt tgcatacttc tgcctgctgg 8580
ggagcctggg gactttccac acctggttgc tgactaattg agatgcatgc tttgcatact 8640
tctgcctgct ggggagcctg gggactttcc acaccctaac tgacacacat tccacagctg 8700
cattaatgaa tcggccaacg cgcggggaga ggcggtttgc gtattgggcg ctcttccgct 8760
tcctcgctca ctgactcgct gcgctcggtc gttcggctgc ggcgagcggt atcagctcac 8820
tcaaaggcgg taatacggtt atccacagaa tcaggggata acgcaggaaa gaacatgtga 8880
gcaaaaggcc agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc gtttttccat 8940
aggctccgcc cccctgacga gcatcacaaa aatcgacgct caagtcagag gtggcgaaac 9000
ccgacaggac tataaagata ccaggcgttt ccccctggaa gctccctcgt gcgctctcct 9060
gttccgaccc tgccgcttac cggatacctg tccgcctttc tcccttcggg aagcgtggcg 9120
ctttctcata gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg 9180
ggctgtgtgc acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt 9240
cttgagtcca acccggtaag acacgactta tcgccactgg cagcagccac tggtaacagg 9300
attagcagag cgaggtatgt aggcggtgct acagagttct tgaagtggtg gcctaactac 9360
ggctacacta gaagaacagt atttggtatc tgcgctctgc tgaagccagt taccttcgga 9420
aaaagagttg gtagctcttg atccggcaaa caaaccaccg ctggtagcgg tggttttttt 9480
gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt 9540
tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt ggtcatgaga 9600
ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt taaatcaatc 9660
taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag tgaggcacct 9720
atctcagcga tctgtctatt tcgttcatcc atagttgcct gactcctgca aaccacgttg 9780
tgtctcaaaa tctctgatgt tacattgcac aagataaaaa tatatcatca tgaacaataa 9840
aactgtctgc ttacataaac agtaatacaa ggggtgttat gagccatatt caacgggaaa 9900
cgtcttgctc gaggccgcga ttaaattcca acatggatgc tgatttatat gggtataaat 9960
gggctcgcga taatgtcggg caatcaggtg cgacaatcta tcgattgtat gggaagcccg 10020
atgcgccaga gttgtttctg aaacatggca aaggtagcgt tgccaatgat gttacagatg 10080
agatggtcag actaaactgg ctgacggaat ttatgcctct tccgaccatc aagcatttta 10140
tccgtactcc tgatgatgca tggttactca ccactgcgat ccccgggaaa acagcattcc 10200
aggtattaga agaatatcct gattcaggtg aaaatattgt tgatgcgctg gcagtgttcc 10260
tgcgccggtt gcattcgatt cctgtttgta attgtccttt taacagcgat cgcgtatttc 10320
gtctcgctca ggcgcaatca cgaatgaata acggtttggt tgatgcgagt gattttgatg 10380
acgagcgtaa tggctggcct gttgaacaag tctggaaaga aatgcataag cttttgccat 10440
tctcaccgga ttcagtcgtc actcatggtg atttctcact tgataacctt atttttgacg 10500
aggggaaatt aataggttgt attgatgttg gacgagtcgg aatcgcagac cgataccagg 10560
atcttgccat cctatggaac tgcctcggtg agttttctcc ttcattacag aaacggcttt 10620
ttcaaaaata tggtattgat aatcctgata tgaataaatt gcagtttcat ttgatgctcg 10680
atgagttttt ctaagggcgg cctgccacca tacccacgcc gaaacaagcg ctcatgagcc 10740
cgaagtggcg agcccgatct tccccatcgg tgatgtcggc gatataggcg ccagcaaccg 10800
cacctgtggc gccggtgatg agggcgcgcc aagtcgacgt ccggcagtc 10849
<210> 29
<211> 11188
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 29
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactatt agatctgatg gccgcgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
gtggtgactg agatgttttc taggaaacac aaaagataca aaaaagaaca cgtggaagga 300
tagccaaaaa ggggggctgc ccccatttcc tgcaccccgc tgcgatggct ggcaccattt 360
ggaagacttc gagatacact gttgagcgca gtaagacaac agtgtatctc gaagtcttcc 420
agatggggcc agccggtcca ctctgtatcc aggccagttc tgcaaggcgt tcgaggacca 480
cccccctccc ctcgccacca gggtggtctc atacagaact tataagattc ccaaatccaa 540
agacatttca cgtttatggt gatttcccag aacacatagc gacatgcaaa tattgcaggg 600
cgccactccc ctgtccctca cagccatctt cctgccaggg cgcacgcgcg ctgggtgttc 660
ccgcctagtg acactgggcc cgcgattcct tggagcgggt tgatgacgtc agcgtttccc 720
atggtgaatc cctaggttct agaaccggtg acgtctccca tggtgaagct tggatctgaa 780
ttcggtacct agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat 840
ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc 900
ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca 960
ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta 1020
tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 1080
tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 1140
cgctattacc atggtcgagg tgagccccac gttctgcttc actctcccca tctccccccc 1200
ctccccaccc ccaattttgt atttatttat tttttaatta ttttgtgcag cgatgggggc 1260
gggggggggg ggggggcgcg cgccaggcgg ggcggggcgg ggcgaggggc ggggcggggc 1320
gaggcggaga ggtgcggcgg cagccaatca gagcggcgcg ctccgaaagt ttccttttat 1380
ggcgaggcgg cggcggcggc ggccctataa aaagcgaagc gcgcggcggg cgggagtcgc 1440
tgcgacgctg ccttcgcccc gtgccccgct ccgccgccgc ctcgcgccgc ccgccccggc 1500
tctgactgac cgcgttactc ccacaggtga gcgggcggga cggcccttct cctccgggct 1560
gtaattagcg cttggtttaa tgacggcttg tttcttttct gtggctgcgt gaaagccttg 1620
aggggctccg ggagctagag cctctgctaa ccatgttcat gccttcttct ttttcctaca 1680
gctcctgggc aacgtgctgg ttattgtgct gtctcatcat tttggcaaag aattcctcga 1740
agatccgaag ggaaagtctt ccacgactgt gggatccgtt cgaagatatc accggttgag 1800
ccaccatgga attcagcagc cccagcagag aggaatgccc caagcctctg agccgggtgt 1860
caatcatggc cggatctctg acaggactgc tgctgcttca ggccgtgtct tgggcttctg 1920
gcgctagacc ttgcatcccc aagagcttcg gctacagcag cgtcgtgtgc gtgtgcaatg 1980
ccacctactg cgacagcttc gaccctccta cctttcctgc tctgggcacc ttcagcagat 2040
acgagagcac cagatccggc agacggatgg aactgagcat gggacccatc caggccaatc 2100
acacaggcac tggcctgctg ctgacactgc agcctgagca gaaattccag aaagtgaaag 2160
gcttcggcgg agccatgaca gatgccgccg ctctgaatat cctggctctg tctccaccag 2220
ctcagaacct gctgctcaag agctacttca gcgaggaagg catcggctac aacatcatca 2280
gagtgcccat ggccagctgc gacttcagca tcaggaccta cacctacgcc gacacacccg 2340
acgatttcca gctgcacaac ttcagcctgc ctgaagagga caccaagctg aagatccctc 2400
tgatccacag agccctgcag ctggcacaaa gacccgtgtc actgctggcc tctccatgga 2460
catctcccac ctggctgaaa acaaatggcg ccgtgaatgg caagggcagc ctgaaaggcc 2520
aacctggcga catctaccac cagacctggg ccagatactt cgtgaagttc ctggacgcct 2580
atgccgagca caagctgcag ttttgggccg tgacagccga gaacgaacct tctgctggac 2640
tgctgagcgg ctaccccttt cagtgcctgg gctttacacc cgagcaccag cgggacttta 2700
tcgcccgtga tctgggaccc acactggcca atagcaccca ccataatgtg cggctgctga 2760
tgctggacga ccagagactg cttctgcccc actgggctaa agtggtgctg acagatcctg 2820
aggccgccaa atacgtgcac ggaatcgccg tgcactggta tctggacttt ctggcccctg 2880
ccaaggccac actgggagag acacacagac tgttccccaa caccatgctg ttcgccagcg 2940
aagcctgtgt gggcagcaag ttttgggaac agagcgtgcg gctcggcagc tgggatagag 3000
gcatgcagta cagccacagc atcatcacca acctgctgta ccacgtcgtc ggctggaccg 3060
actggaatct ggccctgaat cctgaaggcg gccctaactg ggtccgaaac ttcgtggaca 3120
gccccatcat cgtggacatc accaaggaca ccttctacaa gcagcccatg ttctaccacc 3180
tgggacactt cagcaagttc atccccgagg gctctcagcg cgttggactg gtggcttccc 3240
agaagaacga tctggacgcc gtggctctga tgcaccctga tggatctgct gtggtggtgg 3300
tcctgaaccg cagcagcaaa gatgtgcccc tgaccatcaa ggatcccgcc gtgggattcc 3360
tggaaacaat cagccctggc tactccatcc acacctacct gtggcgtaga cagtgacaat 3420
tgttaattaa gtttaaaccc tcgaggccgc aagcttatcg ataatcaacc tctggattac 3480
aaaatttgtg aaagattgac tggtattctt aactatgttg ctccttttac gctatgtgga 3540
tacgctgctt taatgccttt gtatcatgct attgcttccc gtatggcttt cattttctcc 3600
tccttgtata aatcctggtt gctgtctctt tatgaggagt tgtggcccgt tgtcaggcaa 3660
cgtggcgtgg tgtgcactgt gtttgctgac gcaaccccca ctggttgggg cattgccacc 3720
acctgtcagc tcctttccgg gactttcgct ttccccctcc ctattgccac ggcggaactc 3780
atcgccgcct gccttgcccg ctgctggaca ggggctcggc tgttgggcac tgacaattcc 3840
gtggtgttgt cggggaaatc atcgtccttt ccttggctgc tcgcctgtgt tgccacctgg 3900
attctgcgcg ggacgtcctt ctgctacgtc ccttcggccc tcaatccagc ggaccttcct 3960
tcccgcggcc tgctgccggc tctgcggcct cttccgcgtc ttcgccttcg ccctcagacg 4020
agtcggatct ccctttgggc cgcctccccg catcgatacc gtcgactaga gctcgctgat 4080
cagcctcgac tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt 4140
ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat 4200
cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg 4260
gggaggattg ggaagacaat agcaggcatg ctggggagag atccacgata acaaacagct 4320
tttttggggt gaacatattg actgaattcc ctgcaggttg gccactccct ctctgcgcgc 4380
tcgctcgctc actgaggccg cccgggcaaa gcccgggcgt cgggcgacct ttggtcgccc 4440
ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc aactccatca ctaggggttc 4500
ctgcggccgc tcgtacggtc tcgaggaatt cctgcaggat aacttgccaa cctcattcta 4560
aaatgtatat agaagcccaa aagacaataa caaaaatatt cttgtagaac aaaatgggaa 4620
agaatgttcc actaaatatc aagatttaga gcaaagcatg agatgtgtgg ggatagacag 4680
tgaggctgat aaaatagagt agagctcaga aacagaccca ttgatatatg taagtgacct 4740
atgaaaaaaa tatggcattt tacaatggga aaatgatggt ctttttcttt tttagaaaaa 4800
cagggaaata tatttatatg taaaaaataa aagggaaccc atatgtcata ccatacacac 4860
aaaaaaattc cagtgaatta taagtctaaa tggagaaggc aaaactttaa atcttttaga 4920
aaataatata gaagcatgca gaccagcctg gccaacatga tgaaaccctc tctactaata 4980
ataaaatcag tagaactact caggactact ttgagtggga agtccttttc tatgaagact 5040
tctttggcca aaattaggct ctaaatgcaa ggagatagtg catcatgcct ggctgcactt 5100
actgataaat gatgttatca ccatctttaa ccaaatgcac aggaacaagt tatggtactg 5160
atgtgctgga ttgagaagga gctctacttc cttgacagga cacatttgta tcaacttaaa 5220
aaagcagatt tttgccagca gaactattca ttcagaggta ggaaacttag aatagatgat 5280
gtcactgatt agcatggctt ccccatctcc acagctgctt cccacccagg ttgcccacag 5340
ttgagtttgt ccagtgctca gggctgccca ctctcagtaa gaagccccac accagcccct 5400
ctccaaatat gttggctgtt ccttccatta aagtgacccc actttagagc agcaagtgga 5460
tttctgtttc ttacagttca ggaaggagga gtcagctgtg agaacctgga gcctgagatg 5520
cttctaagtc ccactgctac tggggtcagg gaagccagac tccagcatca gcagtcagga 5580
gcactaagcc cttgccaaca tcctgtttct cagagaaact gcttccatta taatggttgt 5640
ccttttttaa gctatcaagc caaacaacca gtgtctacca ttattctcat cacctgaagc 5700
caagggttct agcaaaagtc aagctgtctt gtaatggttg atgtgcctcc agcttctgtc 5760
ttcagtcact ccactcttag cctgctctga atcaactctg accacagttc cctggagccc 5820
ctgccacctg ctgcccctgc caccttctcc atctgcagtg ctgtgcagcc ttctgcactc 5880
ttgcagagct aataggtgga gacttgaagg aagaggagga aagtttctca taatagcctt 5940
gctgcaagct caaatgggag gtgggcactg tgcccaggag ccttggagca aaggctgtgc 6000
ccaacctctg actgcatcca ggtttggtct tgacagagat aagaagccct ggcttttgga 6060
gccaaaatct aggtcagact taggcaggat tctcaaagtt tatcagcaga acatgaggca 6120
gaagaccctt tctgctccag cttcttcagg ctcaaccttc atcagaatag atagaaagag 6180
aggctgtgag ggttcttaaa acagaagcaa atctgactca gagaataaac aacctcctag 6240
taaactacag cttagacaga gcatctggtg gtgagtgtgc tcagtgtcct actcaactgt 6300
ctggtatcag ccctcatgag gacttctctt ctttccctca tagacctcca tctctgtttt 6360
ccttagcctg cagaaatctg gatggctatt cacagaatgc ctgtgctttc agagttgcat 6420
tttttctctg gtattctggt tcaagcattt gaaggtagga aaggttctcc aagtgcaaga 6480
aagccagccc tgagcctcaa ctgcctggct agtgtggtca gtaggatgca aaggctgttg 6540
aatgccacaa ggccaaactt taacctgtgt accacaagcc tagcagcaga ggcagctctg 6600
ctcactggaa ctctctgtct tctttctcct gagccttttc ttttcctgag ttttctagct 6660
ctcctcaacc ttacctctgc cctacccagg acaaacccaa gagccactgt ttctgtgatg 6720
tcctctccag ccctaattag gcatcatgac ttcagcctga ccttccatgc tcagaagcag 6780
tgctaatcca cttcagatga gctgctctat gcaacacagg cagagcctac aaacctttgc 6840
accagagccc tccacatatc agtgtttgtt catactcact tcaacagcaa atgtgactgc 6900
tgagattaag attttacaca agatggtctg taatttcaca gttagtttta tcccattagg 6960
tatgaaagaa ttagcataat tccccttaaa catgaatgaa tcttagattt tttaataaat 7020
agttttggaa gtaaagacag agacatcagg agcacaagga atagcctgag aggacaaaca 7080
gaacaagaaa gagtctggaa atacacagga tgttcttggc ctcctcaaag caagtgcaag 7140
cagatagtac cagcagcccc aggctatcag agcccagtga agagaagtac catgaaagcc 7200
acagctctaa ccaccctgtt ccagagtgac agacagtccc caagacaagc cagcctgagc 7260
cagagagaga actgcaagag aaagtttcta atttaggttc tgttagattc agacaagtgc 7320
aggtcatcct ctctccacag ctactcacct ctccagccta acaaagcctg cagtccacac 7380
tccaaccctg gtgtctcacc tcctagcctc tcccaacatc ctgctctctg accatcttct 7440
gcatctctca tctcaccatc tcccactgtc tacagcctac tcttgcaact accatctcat 7500
tttctgacat cctgtctaca tcttctgcca tactctgcca tctaccatac cacctcttac 7560
catctaccac accatctttt atctccatcc ctctcagaag cctccaagct gaatcctgct 7620
ttatgtgttc atctcagccc ctgcatggaa agctgacccc agaggcagaa ctattcccag 7680
agagcttggc caagaaaaac aaaactacca gcctggccag gctcaggagt agtaagctgc 7740
agtgtctgtt gtgttctagc ttcaacagct gcaggagttc cactctcaaa tgctccacat 7800
ttctcacatc ctcctgattc tggtcactac ccatcttcaa agaacagaat atctcacatc 7860
agcatactgt gaaggactag tcatgggtgc agctgctcag agctgcaaag tcattctgga 7920
tggtggagag cttacaaaca tttcatgatg ctccccccgc tctgatggct ggagcccaat 7980
ccctacacag actcctgctg tatgtgtttt cctttcactc tgagccacag ccagagggca 8040
ggcattcagt ctcctcttca ggctggggct ggggcactga gaactcaccc aacaccttgc 8100
tctcactcct tctgcaaaac aagaaagagc tttgtgctgc agtagccatg aagaatgaaa 8160
ggaaggcttt aactaaaaaa tgtcagagat tattttcaac cccttactgt ggatcaccag 8220
caaggaggaa acacaacaca gagacatttt ttcccctcaa attatcaaaa gaatcactgc 8280
atttgttaaa gagagcaact gaatcaggaa gcagagtttt gaacatatca gaagttagga 8340
atctgcatca gagacaaatg cagtcatggt tgtttgctgc ataccagccc taatcattag 8400
aagcctcatg gacttcaaac atcattccct ctgacaagat gctctagcct aactccatga 8460
gataaaataa atctgccttt cagagccaaa gaagagtcca ccagcttctt ctcagtgtga 8520
acaagagctc cagtcaggtt agtcagtcca gtgcagtaga ggagaccagt ctgcatcctc 8580
taattttcaa aggcaagaag atttgtttac cctggacacc aggcacaagt gaggtcacag 8640
agctcttaga tatgcagtcc tcatgagtga ggagactaaa gcgcatgcca tcaagacttc 8700
agtgtagaga aaacctccaa aaaagcctcc tcactacttc tggaatagct cagaggccga 8760
ggcggcctcg gcctctgcat aaataaaaaa aattagtcag ccatggggcg gagaatgggc 8820
ggaactgggc ggagttaggg gcgggatggg cggagttagg ggcgggacta tggttgctga 8880
ctaattgaga tgcatgcttt gcatacttct gcctgctggg gagcctgggg actttccaca 8940
cctggttgct gactaattga gatgcatgct ttgcatactt ctgcctgctg gggagcctgg 9000
ggactttcca caccctaact gacacacatt ccacagctgc attaatgaat cggccaacgc 9060
gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac tgactcgctg 9120
cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta 9180
tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc 9240
aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc ccctgacgag 9300
catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact ataaagatac 9360
caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct gccgcttacc 9420
ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcatag ctcacgctgt 9480
aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc 9540
gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa cccggtaaga 9600
cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc gaggtatgta 9660
ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag aagaacagta 9720
tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg tagctcttga 9780
tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca gcagattacg 9840
cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc tgacgctcag 9900
tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag gatcttcacc 9960
tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata tgagtaaact 10020
tggtctgaca gttaccaatg cttaatcagt gaggcaccta tctcagcgat ctgtctattt 10080
cgttcatcca tagttgcctg actcctgcaa accacgttgt gtctcaaaat ctctgatgtt 10140
acattgcaca agataaaaat atatcatcat gaacaataaa actgtctgct tacataaaca 10200
gtaatacaag gggtgttatg agccatattc aacgggaaac gtcttgctcg aggccgcgat 10260
taaattccaa catggatgct gatttatatg ggtataaatg ggctcgcgat aatgtcgggc 10320
aatcaggtgc gacaatctat cgattgtatg ggaagcccga tgcgccagag ttgtttctga 10380
aacatggcaa aggtagcgtt gccaatgatg ttacagatga gatggtcaga ctaaactggc 10440
tgacggaatt tatgcctctt ccgaccatca agcattttat ccgtactcct gatgatgcat 10500
ggttactcac cactgcgatc cccgggaaaa cagcattcca ggtattagaa gaatatcctg 10560
attcaggtga aaatattgtt gatgcgctgg cagtgttcct gcgccggttg cattcgattc 10620
ctgtttgtaa ttgtcctttt aacagcgatc gcgtatttcg tctcgctcag gcgcaatcac 10680
gaatgaataa cggtttggtt gatgcgagtg attttgatga cgagcgtaat ggctggcctg 10740
ttgaacaagt ctggaaagaa atgcataagc ttttgccatt ctcaccggat tcagtcgtca 10800
ctcatggtga tttctcactt gataacctta tttttgacga ggggaaatta ataggttgta 10860
ttgatgttgg acgagtcgga atcgcagacc gataccagga tcttgccatc ctatggaact 10920
gcctcggtga gttttctcct tcattacaga aacggctttt tcaaaaatat ggtattgata 10980
atcctgatat gaataaattg cagtttcatt tgatgctcga tgagtttttc taagggcggc 11040
ctgccaccat acccacgccg aaacaagcgc tcatgagccc gaagtggcga gcccgatctt 11100
ccccatcggt gatgtcggcg atataggcgc cagcaaccgc acctgtggcg ccggtgatga 11160
gggcgcgcca agtcgacgtc cggcagtc 11188
<210> 30
<211> 11174
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 30
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtcggt ggtgactgag atgttttcta ggaaacacaa 300
aagatacaaa aaagaacacg tggaaggata gccaaaaagg ggggctgccc ccatttcctg 360
caccccgctg cgatggctgg caccatttgg aagacttcga gatacactgt tgagcgcagt 420
aagacaacag tgtatctcga agtcttccag atggggccag ccggtccact ctgtatccag 480
gccagttctg caaggcgttc gaggaccacc cccctcccct cgccaccagg gtggtctcat 540
acagaactta taagattccc aaatccaaag acatttcacg tttatggtga tttcccagaa 600
cacatagcga catgcaaata ttgcagggcg ccactcccct gtccctcaca gccatcttcc 660
tgccagggcg cacgcgcgct gggtgttccc gcctagtgac actgggcccg cgattccttg 720
gagcgggttg atgacgtcag cgtttcccat ggtgaagctt ggatctgaat tcggtaccct 780
agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc 840
gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg 900
acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa 960
tgggtggact atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca 1020
agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac 1080
atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc 1140
atggtcgagg tgagccccac gttctgcttc actctcccca tctccccccc ctccccaccc 1200
ccaattttgt atttatttat tttttaatta ttttgtgcag cgatgggggc gggggggggg 1260
ggggggcgcg cgccaggcgg ggcggggcgg ggcgaggggc ggggcggggc gaggcggaga 1320
ggtgcggcgg cagccaatca gagcggcgcg ctccgaaagt ttccttttat ggcgaggcgg 1380
cggcggcggc ggccctataa aaagcgaagc gcgcggcggg cgggagtcgc tgcgacgctg 1440
ccttcgcccc gtgccccgct ccgccgccgc ctcgcgccgc ccgccccggc tctgactgac 1500
cgcgttactc ccacaggtga gcgggcggga cggcccttct cctccgggct gtaattagcg 1560
cttggtttaa tgacggcttg ttttctgtgg ctgcgtgaaa gccttgaggg gctccgggag 1620
ctagagcctc tgctaaccat gttcatgcct tcttcttttt cctacagctc ctgggcaacg 1680
tgctggttat tgtgctgtct catcattttg gcaaagaatt cctcgaagat ccgaagggaa 1740
agtcttccac gactgtggga tccgttcgaa gatatcaccg gttgagccac catggaattc 1800
agcagcccca gcagagagga atgccccaag cctctgagcc gggtgtcaat catggccgga 1860
tctctgacag gactgctgct gcttcaggcc gtgtcttggg cttctggcgc tagaccttgc 1920
atccccaaga gcttcggcta cagcagcgtc gtgtgcgtgt gcaatgccac ctactgcgac 1980
agcttcgacc ctcctacctt tcctgctctg ggcaccttca gcagatacga gagcaccaga 2040
tccggcagac ggatggaact gagcatggga cccatccagg ccaatcacac aggcactggc 2100
ctgctgctga cactgcagcc tgagcagaaa ttccagaaag tgaaaggctt cggcggagcc 2160
atgacagatg ccgccgctct gaatatcctg gctctgtctc caccagctca gaacctgctg 2220
ctcaagagct acttcagcga ggaaggcatc ggctacaaca tcatcagagt gcccatggcc 2280
agctgcgact tcagcatcag gacctacacc tacgccgaca cacccgacga tttccagctg 2340
cacaacttca gcctgcctga agaggacacc aagctgaaga tccctctgat ccacagagcc 2400
ctgcagctgg cacaaagacc cgtgtcactg ctggcctctc catggacatc tcccacctgg 2460
ctgaaaacaa atggcgccgt gaatggcaag ggcagcctga aaggccaacc tggcgacatc 2520
taccaccaga cctgggccag atacttcgtg aagttcctgg acgcctatgc cgagcacaag 2580
ctgcagtttt gggccgtgac agccgagaac gaaccttctg ctggactgct gagcggctac 2640
ccctttcagt gcctgggctt tacacccgag caccagcggg actttatcgc ccgtgatctg 2700
ggacccacac tggccaatag cacccaccat aatgtgcggc tgctgatgct ggacgaccag 2760
agactgcttc tgccccactg ggctaaagtg gtgctgacag atcctgaggc cgccaaatac 2820
gtgcacggaa tcgccgtgca ctggtatctg gactttctgg cccctgccaa ggccacactg 2880
ggagagacac acagactgtt ccccaacacc atgctgttcg ccagcgaagc ctgtgtgggc 2940
agcaagtttt gggaacagag cgtgcggctc ggcagctggg atagaggcat gcagtacagc 3000
cacagcatca tcaccaacct gctgtaccac gtcgtcggct ggaccgactg gaatctggcc 3060
ctgaatcctg aaggcggccc taactgggtc cgaaacttcg tggacagccc catcatcgtg 3120
gacatcacca aggacacctt ctacaagcag cccatgttct accacctggg acacttcagc 3180
aagttcatcc ccgagggctc tcagcgcgtt ggactggtgg cttcccagaa gaacgatctg 3240
gacgccgtgg ctctgatgca ccctgatgga tctgctgtgg tggtggtcct gaaccgcagc 3300
agcaaagatg tgcccctgac catcaaggat cccgccgtgg gattcctgga aacaatcagc 3360
cctggctact ccatccacac ctacctgtgg cgtagacagt gacaattgtt aattaagttt 3420
aaaccctcga ggccgcaagc ttatcgataa tcaacctctg gattacaaaa tttgtgaaag 3480
attgactggt attcttaact atgttgctcc ttttacgcta tgtggatacg ctgctttaat 3540
gcctttgtat catgctattg cttcccgtat ggctttcatt ttctcctcct tgtataaatc 3600
ctggttgctg tctctttatg aggagttgtg gcccgttgtc aggcaacgtg gcgtggtgtg 3660
cactgtgttt gctgacgcaa cccccactgg ttggggcatt gccaccacct gtcagctcct 3720
ttccgggact ttcgctttcc ccctccctat tgccacggcg gaactcatcg ccgcctgcct 3780
tgcccgctgc tggacagggg ctcggctgtt gggcactgac aattccgtgg tgttgtcggg 3840
gaaatcatcg tcctttcctt ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac 3900
gtccttctgc tacgtccctt cggccctcaa tccagcggac cttccttccc gcggcctgct 3960
gccggctctg cggcctcttc cgcgtcttcg ccttcgccct cagacgagtc ggatctccct 4020
ttgggccgcc tccccgcatc gataccgtcg actagagctc gctgatcagc ctcgactgtg 4080
ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa 4140
ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt 4200
aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa 4260
gacaatagca ggcatgctgg ggagagatcc acgataacaa acagcttttt tggggtgaac 4320
atattgactg aattccctgc aggttggcca ctccctctct gcgcgctcgc tcgctcactg 4380
aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg tcgcccggcc tcagtgagcg 4440
agcgagcgcg cagagaggga gtggccaact ccatcactag gggttcctgc ggccgctcgt 4500
acggtctcga ggaattcctg caggataact tgccaacctc attctaaaat gtatatagaa 4560
gcccaaaaga caataacaaa aatattcttg tagaacaaaa tgggaaagaa tgttccacta 4620
aatatcaaga tttagagcaa agcatgagat gtgtggggat agacagtgag gctgataaaa 4680
tagagtagag ctcagaaaca gacccattga tatatgtaag tgacctatga aaaaaatatg 4740
gcattttaca atgggaaaat gatggtcttt ttctttttta gaaaaacagg gaaatatatt 4800
tatatgtaaa aaataaaagg gaacccatat gtcataccat acacacaaaa aaattccagt 4860
gaattataag tctaaatgga gaaggcaaaa ctttaaatct tttagaaaat aatatagaag 4920
catgcagacc agcctggcca acatgatgaa accctctcta ctaataataa aatcagtaga 4980
actactcagg actactttga gtgggaagtc cttttctatg aagacttctt tggccaaaat 5040
taggctctaa atgcaaggag atagtgcatc atgcctggct gcacttactg ataaatgatg 5100
ttatcaccat ctttaaccaa atgcacagga acaagttatg gtactgatgt gctggattga 5160
gaaggagctc tacttccttg acaggacaca tttgtatcaa cttaaaaaag cagatttttg 5220
ccagcagaac tattcattca gaggtaggaa acttagaata gatgatgtca ctgattagca 5280
tggcttcccc atctccacag ctgcttccca cccaggttgc ccacagttga gtttgtccag 5340
tgctcagggc tgcccactct cagtaagaag ccccacacca gcccctctcc aaatatgttg 5400
gctgttcctt ccattaaagt gaccccactt tagagcagca agtggatttc tgtttcttac 5460
agttcaggaa ggaggagtca gctgtgagaa cctggagcct gagatgcttc taagtcccac 5520
tgctactggg gtcagggaag ccagactcca gcatcagcag tcaggagcac taagcccttg 5580
ccaacatcct gtttctcaga gaaactgctt ccattataat ggttgtcctt ttttaagcta 5640
tcaagccaaa caaccagtgt ctaccattat tctcatcacc tgaagccaag ggttctagca 5700
aaagtcaagc tgtcttgtaa tggttgatgt gcctccagct tctgtcttca gtcactccac 5760
tcttagcctg ctctgaatca actctgacca cagttccctg gagcccctgc cacctgctgc 5820
ccctgccacc ttctccatct gcagtgctgt gcagccttct gcactcttgc agagctaata 5880
ggtggagact tgaaggaaga ggaggaaagt ttctcataat agccttgctg caagctcaaa 5940
tgggaggtgg gcactgtgcc caggagcctt ggagcaaagg ctgtgcccaa cctctgactg 6000
catccaggtt tggtcttgac agagataaga agccctggct tttggagcca aaatctaggt 6060
cagacttagg caggattctc aaagtttatc agcagaacat gaggcagaag accctttctg 6120
ctccagcttc ttcaggctca accttcatca gaatagatag aaagagaggc tgtgagggtt 6180
cttaaaacag aagcaaatct gactcagaga ataaacaacc tcctagtaaa ctacagctta 6240
gacagagcat ctggtggtga gtgtgctcag tgtcctactc aactgtctgg tatcagccct 6300
catgaggact tctcttcttt ccctcataga cctccatctc tgttttcctt agcctgcaga 6360
aatctggatg gctattcaca gaatgcctgt gctttcagag ttgcattttt tctctggtat 6420
tctggttcaa gcatttgaag gtaggaaagg ttctccaagt gcaagaaagc cagccctgag 6480
cctcaactgc ctggctagtg tggtcagtag gatgcaaagg ctgttgaatg ccacaaggcc 6540
aaactttaac ctgtgtacca caagcctagc agcagaggca gctctgctca ctggaactct 6600
ctgtcttctt tctcctgagc cttttctttt cctgagtttt ctagctctcc tcaaccttac 6660
ctctgcccta cccaggacaa acccaagagc cactgtttct gtgatgtcct ctccagccct 6720
aattaggcat catgacttca gcctgacctt ccatgctcag aagcagtgct aatccacttc 6780
agatgagctg ctctatgcaa cacaggcaga gcctacaaac ctttgcacca gagccctcca 6840
catatcagtg tttgttcata ctcacttcaa cagcaaatgt gactgctgag attaagattt 6900
tacacaagat ggtctgtaat ttcacagtta gttttatccc attaggtatg aaagaattag 6960
cataattccc cttaaacatg aatgaatctt agatttttta ataaatagtt ttggaagtaa 7020
agacagagac atcaggagca caaggaatag cctgagagga caaacagaac aagaaagagt 7080
ctggaaatac acaggatgtt cttggcctcc tcaaagcaag tgcaagcaga tagtaccagc 7140
agccccaggc tatcagagcc cagtgaagag aagtaccatg aaagccacag ctctaaccac 7200
cctgttccag agtgacagac agtccccaag acaagccagc ctgagccaga gagagaactg 7260
caagagaaag tttctaattt aggttctgtt agattcagac aagtgcaggt catcctctct 7320
ccacagctac tcacctctcc agcctaacaa agcctgcagt ccacactcca accctggtgt 7380
ctcacctcct agcctctccc aacatcctgc tctctgacca tcttctgcat ctctcatctc 7440
accatctccc actgtctaca gcctactctt gcaactacca tctcattttc tgacatcctg 7500
tctacatctt ctgccatact ctgccatcta ccataccacc tcttaccatc taccacacca 7560
tcttttatct ccatccctct cagaagcctc caagctgaat cctgctttat gtgttcatct 7620
cagcccctgc atggaaagct gaccccagag gcagaactat tcccagagag cttggccaag 7680
aaaaacaaaa ctaccagcct ggccaggctc aggagtagta agctgcagtg tctgttgtgt 7740
tctagcttca acagctgcag gagttccact ctcaaatgct ccacatttct cacatcctcc 7800
tgattctggt cactacccat cttcaaagaa cagaatatct cacatcagca tactgtgaag 7860
gactagtcat gggtgcagct gctcagagct gcaaagtcat tctggatggt ggagagctta 7920
caaacatttc atgatgctcc ccccgctctg atggctggag cccaatccct acacagactc 7980
ctgctgtatg tgttttcctt tcactctgag ccacagccag agggcaggca ttcagtctcc 8040
tcttcaggct ggggctgggg cactgagaac tcacccaaca ccttgctctc actccttctg 8100
caaaacaaga aagagctttg tgctgcagta gccatgaaga atgaaaggaa ggctttaact 8160
aaaaaatgtc agagattatt ttcaacccct tactgtggat caccagcaag gaggaaacac 8220
aacacagaga cattttttcc cctcaaatta tcaaaagaat cactgcattt gttaaagaga 8280
gcaactgaat caggaagcag agttttgaac atatcagaag ttaggaatct gcatcagaga 8340
caaatgcagt catggttgtt tgctgcatac cagccctaat cattagaagc ctcatggact 8400
tcaaacatca ttccctctga caagatgctc tagcctaact ccatgagata aaataaatct 8460
gcctttcaga gccaaagaag agtccaccag cttcttctca gtgtgaacaa gagctccagt 8520
caggttagtc agtccagtgc agtagaggag accagtctgc atcctctaat tttcaaaggc 8580
aagaagattt gtttaccctg gacaccaggc acaagtgagg tcacagagct cttagatatg 8640
cagtcctcat gagtgaggag actaaagcgc atgccatcaa gacttcagtg tagagaaaac 8700
ctccaaaaaa gcctcctcac tacttctgga atagctcaga ggccgaggcg gcctcggcct 8760
ctgcataaat aaaaaaaatt agtcagccat ggggcggaga atgggcggaa ctgggcggag 8820
ttaggggcgg gatgggcgga gttaggggcg ggactatggt tgctgactaa ttgagatgca 8880
tgctttgcat acttctgcct gctggggagc ctggggactt tccacacctg gttgctgact 8940
aattgagatg catgctttgc atacttctgc ctgctgggga gcctggggac tttccacacc 9000
ctaactgaca cacattccac agctgcatta atgaatcggc caacgcgcgg ggagaggcgg 9060
tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg 9120
gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca cagaatcagg 9180
ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa 9240
ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc acaaaaatcg 9300
acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg cgtttccccc 9360
tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat acctgtccgc 9420
ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt atctcagttc 9480
ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc agcccgaccg 9540
ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg acttatcgcc 9600
actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg gtgctacaga 9660
gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg gtatctgcgc 9720
tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg gcaaacaaac 9780
caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 9840
atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 9900
acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga tccttttaaa 9960
ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt ctgacagtta 10020
ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt catccatagt 10080
tgcctgactc ctgcaaacca cgttgtgtct caaaatctct gatgttacat tgcacaagat 10140
aaaaatatat catcatgaac aataaaactg tctgcttaca taaacagtaa tacaaggggt 10200
gttatgagcc atattcaacg ggaaacgtct tgctcgaggc cgcgattaaa ttccaacatg 10260
gatgctgatt tatatgggta taaatgggct cgcgataatg tcgggcaatc aggtgcgaca 10320
atctatcgat tgtatgggaa gcccgatgcg ccagagttgt ttctgaaaca tggcaaaggt 10380
agcgttgcca atgatgttac agatgagatg gtcagactaa actggctgac ggaatttatg 10440
cctcttccga ccatcaagca ttttatccgt actcctgatg atgcatggtt actcaccact 10500
gcgatccccg ggaaaacagc attccaggta ttagaagaat atcctgattc aggtgaaaat 10560
attgttgatg cgctggcagt gttcctgcgc cggttgcatt cgattcctgt ttgtaattgt 10620
ccttttaaca gcgatcgcgt atttcgtctc gctcaggcgc aatcacgaat gaataacggt 10680
ttggttgatg cgagtgattt tgatgacgag cgtaatggct ggcctgttga acaagtctgg 10740
aaagaaatgc ataagctttt gccattctca ccggattcag tcgtcactca tggtgatttc 10800
tcacttgata accttatttt tgacgagggg aaattaatag gttgtattga tgttggacga 10860
gtcggaatcg cagaccgata ccaggatctt gccatcctat ggaactgcct cggtgagttt 10920
tctccttcat tacagaaacg gctttttcaa aaatatggta ttgataatcc tgatatgaat 10980
aaattgcagt ttcatttgat gctcgatgag tttttctaag ggcggcctgc caccataccc 11040
acgccgaaac aagcgctcat gagcccgaag tggcgagccc gatcttcccc atcggtgatg 11100
tcggcgatat aggcgccagc aaccgcacct gtggcgccgg tgatgagggc gcgccaagtc 11160
gacgtccggc agtc 11174
<210> 31
<211> 10841
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 31
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctccgg gctgtaatta 1080
gcgcttggtt taatgacggc ttgtctggag gcttgctttg ggctgtatgc tgagggtatc 1140
aagactacga attttggcct ctgactgatt cgtagcttat accctcagga cacaaggccc 1200
tttatcagca ctcacatgga acaaatggcc accgtgggag gatgacaatt tctgtggctg 1260
cgtgaaagcc ttgaggggct ccgggagcta gagcctctgc taaccatgtt catgccttct 1320
tctttttcct acagctcctg ggcaacgtgc tggttattgt gctgtctcat cattttggca 1380
aagaattcct cgaagatccg aagggaaagt cttccacgac tgtgggatcc gttcgaagat 1440
atcaccggtt gagccaccat ggaattcagc agccccagca gagaggaatg ccccaagcct 1500
ctgagccggg tgtcaatcat ggccggatct ctgacaggac tgctgctgct tcaggccgtg 1560
tcttgggctt ctggcgctag accttgcatc cccaagagct tcggctacag cagcgtcgtg 1620
tgcgtgtgca atgccaccta ctgcgacagc ttcgaccctc ctacctttcc tgctctgggc 1680
accttcagca gatacgagag caccagatcc ggcagacgga tggaactgag catgggaccc 1740
atccaggcca atcacacagg cactggcctg ctgctgacac tgcagcctga gcagaaattc 1800
cagaaagtga aaggcttcgg cggagccatg acagatgccg ccgctctgaa tatcctggct 1860
ctgtctccac cagctcagaa cctgctgctc aagagctact tcagcgagga aggcatcggc 1920
tacaacatca tcagagtgcc catggccagc tgcgacttca gcatcaggac ctacacctac 1980
gccgacacac ccgacgattt ccagctgcac aacttcagcc tgcctgaaga ggacaccaag 2040
ctgaagatcc ctctgatcca cagagccctg cagctggcac aaagacccgt gtcactgctg 2100
gcctctccat ggacatctcc cacctggctg aaaacaaatg gcgccgtgaa tggcaagggc 2160
agcctgaaag gccaacctgg cgacatctac caccagacct gggccagata cttcgtgaag 2220
ttcctggacg cctatgccga gcacaagctg cagttttggg ccgtgacagc cgagaacgaa 2280
ccttctgctg gactgctgag cggctacccc tttcagtgcc tgggctttac acccgagcac 2340
cagcgggact ttatcgcccg tgatctggga cccacactgg ccaatagcac ccaccataat 2400
gtgcggctgc tgatgctgga cgaccagaga ctgcttctgc cccactgggc taaagtggtg 2460
ctgacagatc ctgaggccgc caaatacgtg cacggaatcg ccgtgcactg gtatctggac 2520
tttctggccc ctgccaaggc cacactggga gagacacaca gactgttccc caacaccatg 2580
ctgttcgcca gcgaagcctg tgtgggcagc aagttttggg aacagagcgt gcggctcggc 2640
agctgggata gaggcatgca gtacagccac agcatcatca ccaacctgct gtaccacgtc 2700
gtcggctgga ccgactggaa tctggccctg aatcctgaag gcggccctaa ctgggtccga 2760
aacttcgtgg acagccccat catcgtggac atcaccaagg acaccttcta caagcagccc 2820
atgttctacc acctgggaca cttcagcaag ttcatccccg agggctctca gcgcgttgga 2880
ctggtggctt cccagaagaa cgatctggac gccgtggctc tgatgcaccc tgatggatct 2940
gctgtggtgg tggtcctgaa ccgcagcagc aaagatgtgc ccctgaccat caaggatccc 3000
gccgtgggat tcctggaaac aatcagccct ggctactcca tccacaccta cctgtggcgt 3060
agacagtgac aattgttaat taagtttaaa ccctcgaggc cgcaagctta tcgataatca 3120
acctctggat tacaaaattt gtgaaagatt gactggtatt cttaactatg ttgctccttt 3180
tacgctatgt ggatacgctg ctttaatgcc tttgtatcat gctattgctt cccgtatggc 3240
tttcattttc tcctccttgt ataaatcctg gttgctgtct ctttatgagg agttgtggcc 3300
cgttgtcagg caacgtggcg tggtgtgcac tgtgtttgct gacgcaaccc ccactggttg 3360
gggcattgcc accacctgtc agctcctttc cgggactttc gctttccccc tccctattgc 3420
cacggcggaa ctcatcgccg cctgccttgc ccgctgctgg acaggggctc ggctgttggg 3480
cactgacaat tccgtggtgt tgtcggggaa atcatcgtcc tttccttggc tgctcgcctg 3540
tgttgccacc tggattctgc gcgggacgtc cttctgctac gtcccttcgg ccctcaatcc 3600
agcggacctt ccttcccgcg gcctgctgcc ggctctgcgg cctcttccgc gtcttcgcct 3660
tcgccctcag acgagtcgga tctccctttg ggccgcctcc ccgcatcgat accgtcgact 3720
agagctcgct gatcagcctc gactgtgcct tctagttgcc agccatctgt tgtttgcccc 3780
tcccccgtgc cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat 3840
gaggaaattg catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg 3900
caggacagca agggggagga ttgggaagac aatagcaggc atgctgggga gagatccacg 3960
ataacaaaca gcttttttgg ggtgaacata ttgactgaat tccctgcagg ttggccactc 4020
cctctctgcg cgctcgctcg ctcactgagg ccgcccgggc aaagcccggg cgtcgggcga 4080
cctttggtcg cccggcctca gtgagcgagc gagcgcgcag agagggagtg gccaactcca 4140
tcactagggg ttcctgcggc cgctcgtacg gtctcgagga attcctgcag gataacttgc 4200
caacctcatt ctaaaatgta tatagaagcc caaaagacaa taacaaaaat attcttgtag 4260
aacaaaatgg gaaagaatgt tccactaaat atcaagattt agagcaaagc atgagatgtg 4320
tggggataga cagtgaggct gataaaatag agtagagctc agaaacagac ccattgatat 4380
atgtaagtga cctatgaaaa aaatatggca ttttacaatg ggaaaatgat ggtctttttc 4440
ttttttagaa aaacagggaa atatatttat atgtaaaaaa taaaagggaa cccatatgtc 4500
ataccataca cacaaaaaaa ttccagtgaa ttataagtct aaatggagaa ggcaaaactt 4560
taaatctttt agaaaataat atagaagcat gcagaccagc ctggccaaca tgatgaaacc 4620
ctctctacta ataataaaat cagtagaact actcaggact actttgagtg ggaagtcctt 4680
ttctatgaag acttctttgg ccaaaattag gctctaaatg caaggagata gtgcatcatg 4740
cctggctgca cttactgata aatgatgtta tcaccatctt taaccaaatg cacaggaaca 4800
agttatggta ctgatgtgct ggattgagaa ggagctctac ttccttgaca ggacacattt 4860
gtatcaactt aaaaaagcag atttttgcca gcagaactat tcattcagag gtaggaaact 4920
tagaatagat gatgtcactg attagcatgg cttccccatc tccacagctg cttcccaccc 4980
aggttgccca cagttgagtt tgtccagtgc tcagggctgc ccactctcag taagaagccc 5040
cacaccagcc cctctccaaa tatgttggct gttccttcca ttaaagtgac cccactttag 5100
agcagcaagt ggatttctgt ttcttacagt tcaggaagga ggagtcagct gtgagaacct 5160
ggagcctgag atgcttctaa gtcccactgc tactggggtc agggaagcca gactccagca 5220
tcagcagtca ggagcactaa gcccttgcca acatcctgtt tctcagagaa actgcttcca 5280
ttataatggt tgtccttttt taagctatca agccaaacaa ccagtgtcta ccattattct 5340
catcacctga agccaagggt tctagcaaaa gtcaagctgt cttgtaatgg ttgatgtgcc 5400
tccagcttct gtcttcagtc actccactct tagcctgctc tgaatcaact ctgaccacag 5460
ttccctggag cccctgccac ctgctgcccc tgccaccttc tccatctgca gtgctgtgca 5520
gccttctgca ctcttgcaga gctaataggt ggagacttga aggaagagga ggaaagtttc 5580
tcataatagc cttgctgcaa gctcaaatgg gaggtgggca ctgtgcccag gagccttgga 5640
gcaaaggctg tgcccaacct ctgactgcat ccaggtttgg tcttgacaga gataagaagc 5700
cctggctttt ggagccaaaa tctaggtcag acttaggcag gattctcaaa gtttatcagc 5760
agaacatgag gcagaagacc ctttctgctc cagcttcttc aggctcaacc ttcatcagaa 5820
tagatagaaa gagaggctgt gagggttctt aaaacagaag caaatctgac tcagagaata 5880
aacaacctcc tagtaaacta cagcttagac agagcatctg gtggtgagtg tgctcagtgt 5940
cctactcaac tgtctggtat cagccctcat gaggacttct cttctttccc tcatagacct 6000
ccatctctgt tttccttagc ctgcagaaat ctggatggct attcacagaa tgcctgtgct 6060
ttcagagttg cattttttct ctggtattct ggttcaagca tttgaaggta ggaaaggttc 6120
tccaagtgca agaaagccag ccctgagcct caactgcctg gctagtgtgg tcagtaggat 6180
gcaaaggctg ttgaatgcca caaggccaaa ctttaacctg tgtaccacaa gcctagcagc 6240
agaggcagct ctgctcactg gaactctctg tcttctttct cctgagcctt ttcttttcct 6300
gagttttcta gctctcctca accttacctc tgccctaccc aggacaaacc caagagccac 6360
tgtttctgtg atgtcctctc cagccctaat taggcatcat gacttcagcc tgaccttcca 6420
tgctcagaag cagtgctaat ccacttcaga tgagctgctc tatgcaacac aggcagagcc 6480
tacaaacctt tgcaccagag ccctccacat atcagtgttt gttcatactc acttcaacag 6540
caaatgtgac tgctgagatt aagattttac acaagatggt ctgtaatttc acagttagtt 6600
ttatcccatt aggtatgaaa gaattagcat aattcccctt aaacatgaat gaatcttaga 6660
ttttttaata aatagttttg gaagtaaaga cagagacatc aggagcacaa ggaatagcct 6720
gagaggacaa acagaacaag aaagagtctg gaaatacaca ggatgttctt ggcctcctca 6780
aagcaagtgc aagcagatag taccagcagc cccaggctat cagagcccag tgaagagaag 6840
taccatgaaa gccacagctc taaccaccct gttccagagt gacagacagt ccccaagaca 6900
agccagcctg agccagagag agaactgcaa gagaaagttt ctaatttagg ttctgttaga 6960
ttcagacaag tgcaggtcat cctctctcca cagctactca cctctccagc ctaacaaagc 7020
ctgcagtcca cactccaacc ctggtgtctc acctcctagc ctctcccaac atcctgctct 7080
ctgaccatct tctgcatctc tcatctcacc atctcccact gtctacagcc tactcttgca 7140
actaccatct cattttctga catcctgtct acatcttctg ccatactctg ccatctacca 7200
taccacctct taccatctac cacaccatct tttatctcca tccctctcag aagcctccaa 7260
gctgaatcct gctttatgtg ttcatctcag cccctgcatg gaaagctgac cccagaggca 7320
gaactattcc cagagagctt ggccaagaaa aacaaaacta ccagcctggc caggctcagg 7380
agtagtaagc tgcagtgtct gttgtgttct agcttcaaca gctgcaggag ttccactctc 7440
aaatgctcca catttctcac atcctcctga ttctggtcac tacccatctt caaagaacag 7500
aatatctcac atcagcatac tgtgaaggac tagtcatggg tgcagctgct cagagctgca 7560
aagtcattct ggatggtgga gagcttacaa acatttcatg atgctccccc cgctctgatg 7620
gctggagccc aatccctaca cagactcctg ctgtatgtgt tttcctttca ctctgagcca 7680
cagccagagg gcaggcattc agtctcctct tcaggctggg gctggggcac tgagaactca 7740
cccaacacct tgctctcact ccttctgcaa aacaagaaag agctttgtgc tgcagtagcc 7800
atgaagaatg aaaggaaggc tttaactaaa aaatgtcaga gattattttc aaccccttac 7860
tgtggatcac cagcaaggag gaaacacaac acagagacat tttttcccct caaattatca 7920
aaagaatcac tgcatttgtt aaagagagca actgaatcag gaagcagagt tttgaacata 7980
tcagaagtta ggaatctgca tcagagacaa atgcagtcat ggttgtttgc tgcataccag 8040
ccctaatcat tagaagcctc atggacttca aacatcattc cctctgacaa gatgctctag 8100
cctaactcca tgagataaaa taaatctgcc tttcagagcc aaagaagagt ccaccagctt 8160
cttctcagtg tgaacaagag ctccagtcag gttagtcagt ccagtgcagt agaggagacc 8220
agtctgcatc ctctaatttt caaaggcaag aagatttgtt taccctggac accaggcaca 8280
agtgaggtca cagagctctt agatatgcag tcctcatgag tgaggagact aaagcgcatg 8340
ccatcaagac ttcagtgtag agaaaacctc caaaaaagcc tcctcactac ttctggaata 8400
gctcagaggc cgaggcggcc tcggcctctg cataaataaa aaaaattagt cagccatggg 8460
gcggagaatg ggcggaactg ggcggagtta ggggcgggat gggcggagtt aggggcggga 8520
ctatggttgc tgactaattg agatgcatgc tttgcatact tctgcctgct ggggagcctg 8580
gggactttcc acacctggtt gctgactaat tgagatgcat gctttgcata cttctgcctg 8640
ctggggagcc tggggacttt ccacacccta actgacacac attccacagc tgcattaatg 8700
aatcggccaa cgcgcgggga gaggcggttt gcgtattggg cgctcttccg cttcctcgct 8760
cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg gtatcagctc actcaaaggc 8820
ggtaatacgg ttatccacag aatcagggga taacgcagga aagaacatgt gagcaaaagg 8880
ccagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg gcgtttttcc ataggctccg 8940
cccccctgac gagcatcaca aaaatcgacg ctcaagtcag aggtggcgaa acccgacagg 9000
actataaaga taccaggcgt ttccccctgg aagctccctc gtgcgctctc ctgttccgac 9060
cctgccgctt accggatacc tgtccgcctt tctcccttcg ggaagcgtgg cgctttctca 9120
tagctcacgc tgtaggtatc tcagttcggt gtaggtcgtt cgctccaagc tgggctgtgt 9180
gcacgaaccc cccgttcagc ccgaccgctg cgccttatcc ggtaactatc gtcttgagtc 9240
caacccggta agacacgact tatcgccact ggcagcagcc actggtaaca ggattagcag 9300
agcgaggtat gtaggcggtg ctacagagtt cttgaagtgg tggcctaact acggctacac 9360
tagaagaaca gtatttggta tctgcgctct gctgaagcca gttaccttcg gaaaaagagt 9420
tggtagctct tgatccggca aacaaaccac cgctggtagc ggtggttttt ttgtttgcaa 9480
gcagcagatt acgcgcagaa aaaaaggatc tcaagaagat cctttgatct tttctacggg 9540
gtctgacgct cagtggaacg aaaactcacg ttaagggatt ttggtcatga gattatcaaa 9600
aaggatcttc acctagatcc ttttaaatta aaaatgaagt tttaaatcaa tctaaagtat 9660
atatgagtaa acttggtctg acagttacca atgcttaatc agtgaggcac ctatctcagc 9720
gatctgtcta tttcgttcat ccatagttgc ctgactcctg caaaccacgt tgtgtctcaa 9780
aatctctgat gttacattgc acaagataaa aatatatcat catgaacaat aaaactgtct 9840
gcttacataa acagtaatac aaggggtgtt atgagccata ttcaacggga aacgtcttgc 9900
tcgaggccgc gattaaattc caacatggat gctgatttat atgggtataa atgggctcgc 9960
gataatgtcg ggcaatcagg tgcgacaatc tatcgattgt atgggaagcc cgatgcgcca 10020
gagttgtttc tgaaacatgg caaaggtagc gttgccaatg atgttacaga tgagatggtc 10080
agactaaact ggctgacgga atttatgcct cttccgacca tcaagcattt tatccgtact 10140
cctgatgatg catggttact caccactgcg atccccggga aaacagcatt ccaggtatta 10200
gaagaatatc ctgattcagg tgaaaatatt gttgatgcgc tggcagtgtt cctgcgccgg 10260
ttgcattcga ttcctgtttg taattgtcct tttaacagcg atcgcgtatt tcgtctcgct 10320
caggcgcaat cacgaatgaa taacggtttg gttgatgcga gtgattttga tgacgagcgt 10380
aatggctggc ctgttgaaca agtctggaaa gaaatgcata agcttttgcc attctcaccg 10440
gattcagtcg tcactcatgg tgatttctca cttgataacc ttatttttga cgaggggaaa 10500
ttaataggtt gtattgatgt tggacgagtc ggaatcgcag accgatacca ggatcttgcc 10560
atcctatgga actgcctcgg tgagttttct ccttcattac agaaacggct ttttcaaaaa 10620
tatggtattg ataatcctga tatgaataaa ttgcagtttc atttgatgct cgatgagttt 10680
ttctaagggc ggcctgccac catacccacg ccgaaacaag cgctcatgag cccgaagtgg 10740
cgagcccgat cttccccatc ggtgatgtcg gcgatatagg cgccagcaac cgcacctgtg 10800
gcgccggtga tgagggcgcg ccaagtcgac gtccggcagt c 10841
<210> 32
<211> 11187
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 32
ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac ctagttataa 60
tagtaatcaa ttacggggtc attagttcat agcccatata tggagttccg cgttacataa 120
cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt gacgtcaata 180
atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca atgggtggag 240
tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc aagtacgccc 300
cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta 360
tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac catggtcgag 420
gtgagcccca cgttctgctt cactctcccc atctcccccc cctccccacc cccaattttg 480
tatttattta ttttttaatt attttgtgca gcgatggggg cggggggggg gggggggcgc 540
gcgccaggcg gggcggggcg gggcgagggg cggggcgggg cgaggcggag aggtgcggcg 600
gcagccaatc agagcggcgc gctccgaaag tttcctttta tggcgaggcg gcggcggcgg 660
cggccctata aaaagcgaag cgcgcggcgg gcgggagtcg ctgcgacgct gccttcgccc 720
cgtgccccgc tccgccgccg cctcgcgccg cccgccccgg ctctgactga ccgcgttact 780
cccacaggtg agcgggcggg acggcccttc tcctccgggc tgtaattagc gcttggttta 840
atgacggctt gtttcttttc tgtggctgcg tgaaagcctt gaggggctcc gggagctaga 900
gcctctgcta accatgttca tgccttcttc tttttcctac agctcctggg caacgtgctg 960
gttattgtgc tgtctcatca ttttggcaaa gaattcctcg aagatccgaa gggaaagtct 1020
tccacgactg tgggatccgt tcgaagatat caccggttga gccaccatgg aattcagcag 1080
ccccagcaga gaggaatgcc ccaagcctct gagccgggtg tcaatcatgg ccggatctct 1140
gacaggactg ctgctgcttc aggccgtgtc ttgggcttct ggcgctagac cttgcatccc 1200
caagagcttc ggctacagca gcgtcgtgtg cgtgtgcaat gccacctact gcgacagctt 1260
cgaccctcct acctttcctg ctctgggcac cttcagcaga tacgagagca ccagatccgg 1320
cagacggatg gaactgagca tgggacccat ccaggccaat cacacaggca ctggcctgct 1380
gctgacactg cagcctgagc agaaattcca gaaagtgaaa ggcttcggcg gagccatgac 1440
agatgccgcc gctctgaata tcctggctct gtctccacca gctcagaacc tgctgctcaa 1500
gagctacttc agcgaggaag gcatcggcta caacatcatc agagtgccca tggccagctg 1560
cgacttcagc atcaggacct acacctacgc cgacacaccc gacgatttcc agctgcacaa 1620
cttcagcctg cctgaagagg acaccaagct gaagatccct ctgatccaca gagccctgca 1680
gctggcacaa agacccgtgt cactgctggc ctctccatgg acatctccca cctggctgaa 1740
aacaaatggc gccgtgaatg gcaagggcag cctgaaaggc caacctggcg acatctacca 1800
ccagacctgg gccagatact tcgtgaagtt cctggacgcc tatgccgagc acaagctgca 1860
gttttgggcc gtgacagccg agaacgaacc ttctgctgga ctgctgagcg gctacccctt 1920
tcagtgcctg ggctttacac ccgagcacca gcgggacttt atcgcccgtg atctgggacc 1980
cacactggcc aatagcaccc accataatgt gcggctgctg atgctggacg accagagact 2040
gcttctgccc cactgggcta aagtggtgct gacagatcct gaggccgcca aatacgtgca 2100
cggaatcgcc gtgcactggt atctggactt tctggcccct gccaaggcca cactgggaga 2160
gacacacaga ctgttcccca acaccatgct gttcgccagc gaagcctgtg tgggcagcaa 2220
gttttgggaa cagagcgtgc ggctcggcag ctgggataga ggcatgcagt acagccacag 2280
catcatcacc aacctgctgt accacgtcgt cggctggacc gactggaatc tggccctgaa 2340
tcctgaaggc ggccctaact gggtccgaaa cttcgtggac agccccatca tcgtggacat 2400
caccaaggac accttctaca agcagcccat gttctaccac ctgggacact tcagcaagtt 2460
catccccgag ggctctcagc gcgttggact ggtggcttcc cagaagaacg atctggacgc 2520
cgtggctctg atgcaccctg atggatctgc tgtggtggtg gtcctgaacc gcagcagcaa 2580
agatgtgccc ctgaccatca aggatcccgc cgtgggattc ctggaaacaa tcagccctgg 2640
ctactccatc cacacctacc tgtggcgtag acagtgacaa ttgttaatta agtttaaacc 2700
ctcgaggccg caagcttatc gataatcaac ctctggatta caaaatttgt gaaagattga 2760
ctggtattct taactatgtt gctcctttta cgctatgtgg atacgctgct ttaatgcctt 2820
tgtatcatgc tattgcttcc cgtatggctt tcattttctc ctccttgtat aaatcctggt 2880
tgctgtctct ttatgaggag ttgtggcccg ttgtcaggca acgtggcgtg gtgtgcactg 2940
tgtttgctga cgcaaccccc actggttggg gcattgccac cacctgtcag ctcctttccg 3000
ggactttcgc tttccccctc cctattgcca cggcggaact catcgccgcc tgccttgccc 3060
gctgctggac aggggctcgg ctgttgggca ctgacaattc cgtggtgttg tcggggaaat 3120
catcgtcctt tccttggctg ctcgcctgtg ttgccacctg gattctgcgc gggacgtcct 3180
tctgctacgt cccttcggcc ctcaatccag cggaccttcc ttcccgcggc ctgctgccgg 3240
ctctgcggcc tcttccgcgt cttcgccttc gccctcagac gagtcggatc tccctttggg 3300
ccgcctcccc gcatcgatac cgtcgactag agctcgctga tcagcctcga ctgtgccttc 3360
tagttgccag ccatctgttg tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc 3420
cactcccact gtcctttcct aataaaatga ggaaattgca tcgcattgtc tgagtaggtg 3480
tcattctatt ctggggggtg gggtggggca ggacagcaag ggggaggatt gggaagacaa 3540
tagcaggcat gctggggaga gatccacgat aacaaacagc ttttttgggg tgaacatatt 3600
gactgaattc cctgcaggtt ggccactccc tctctgcgcg ctcgctcgct cactgaggcc 3660
gcccgggcaa agcccgggcg tcgggcgacc tttggtcgcc cggcctcagt gagcgagcga 3720
gcgcgcagag agggagtggc caactccatc actaggggtt cctgcggccg ctcgtacggt 3780
ctcgaggaat tcctgcagga taacttgcca acctcattct aaaatgtata tagaagccca 3840
aaagacaata acaaaaatat tcttgtagaa caaaatggga aagaatgttc cactaaatat 3900
caagatttag agcaaagcat gagatgtgtg gggatagaca gtgaggctga taaaatagag 3960
tagagctcag aaacagaccc attgatatat gtaagtgacc tatgaaaaaa atatggcatt 4020
ttacaatggg aaaatgatgg tctttttctt ttttagaaaa acagggaaat atatttatat 4080
gtaaaaaata aaagggaacc catatgtcat accatacaca caaaaaaatt ccagtgaatt 4140
ataagtctaa atggagaagg caaaacttta aatcttttag aaaataatat agaagcatgc 4200
agaccagcct ggccaacatg atgaaaccct ctctactaat aataaaatca gtagaactac 4260
tcaggactac tttgagtggg aagtcctttt ctatgaagac ttctttggcc aaaattaggc 4320
tctaaatgca aggagatagt gcatcatgcc tggctgcact tactgataaa tgatgttatc 4380
accatcttta accaaatgca caggaacaag ttatggtact gatgtgctgg attgagaagg 4440
agctctactt ccttgacagg acacatttgt atcaacttaa aaaagcagat ttttgccagc 4500
agaactattc attcagaggt aggaaactta gaatagatga tgtcactgat tagcatggct 4560
tccccatctc cacagctgct tcccacccag gttgcccaca gttgagtttg tccagtgctc 4620
agggctgccc actctcagta agaagcccca caccagcccc tctccaaata tgttggctgt 4680
tccttccatt aaagtgaccc cactttagag cagcaagtgg atttctgttt cttacagttc 4740
aggaaggagg agtcagctgt gagaacctgg agcctgagat gcttctaagt cccactgcta 4800
ctggggtcag ggaagccaga ctccagcatc agcagtcagg agcactaagc ccttgccaac 4860
atcctgtttc tcagagaaac tgcttccatt ataatggttg tcctttttta agctatcaag 4920
ccaaacaacc agtgtctacc attattctca tcacctgaag ccaagggttc tagcaaaagt 4980
caagctgtct tgtaatggtt gatgtgcctc cagcttctgt cttcagtcac tccactctta 5040
gcctgctctg aatcaactct gaccacagtt ccctggagcc cctgccacct gctgcccctg 5100
ccaccttctc catctgcagt gctgtgcagc cttctgcact cttgcagagc taataggtgg 5160
agacttgaag gaagaggagg aaagtttctc ataatagcct tgctgcaagc tcaaatggga 5220
ggtgggcact gtgcccagga gccttggagc aaaggctgtg cccaacctct gactgcatcc 5280
aggtttggtc ttgacagaga taagaagccc tggcttttgg agccaaaatc taggtcagac 5340
ttaggcagga ttctcaaagt ttatcagcag aacatgaggc agaagaccct ttctgctcca 5400
gcttcttcag gctcaacctt catcagaata gatagaaaga gaggctgtga gggttcttaa 5460
aacagaagca aatctgactc agagaataaa caacctccta gtaaactaca gcttagacag 5520
agcatctggt ggtgagtgtg ctcagtgtcc tactcaactg tctggtatca gccctcatga 5580
ggacttctct tctttccctc atagacctcc atctctgttt tccttagcct gcagaaatct 5640
ggatggctat tcacagaatg cctgtgcttt cagagttgca ttttttctct ggtattctgg 5700
ttcaagcatt tgaaggtagg aaaggttctc caagtgcaag aaagccagcc ctgagcctca 5760
actgcctggc tagtgtggtc agtaggatgc aaaggctgtt gaatgccaca aggccaaact 5820
ttaacctgtg taccacaagc ctagcagcag aggcagctct gctcactgga actctctgtc 5880
ttctttctcc tgagcctttt cttttcctga gttttctagc tctcctcaac cttacctctg 5940
ccctacccag gacaaaccca agagccactg tttctgtgat gtcctctcca gccctaatta 6000
ggcatcatga cttcagcctg accttccatg ctcagaagca gtgctaatcc acttcagatg 6060
agctgctcta tgcaacacag gcagagccta caaacctttg caccagagcc ctccacatat 6120
cagtgtttgt tcatactcac ttcaacagca aatgtgactg ctgagattaa gattttacac 6180
aagatggtct gtaatttcac agttagtttt atcccattag gtatgaaaga attagcataa 6240
ttccccttaa acatgaatga atcttagatt ttttaataaa tagttttgga agtaaagaca 6300
gagacatcag gagcacaagg aatagcctga gaggacaaac agaacaagaa agagtctgga 6360
aatacacagg atgttcttgg cctcctcaaa gcaagtgcaa gcagatagta ccagcagccc 6420
caggctatca gagcccagtg aagagaagta ccatgaaagc cacagctcta accaccctgt 6480
tccagagtga cagacagtcc ccaagacaag ccagcctgag ccagagagag aactgcaaga 6540
gaaagtttct aatttaggtt ctgttagatt cagacaagtg caggtcatcc tctctccaca 6600
gctactcacc tctccagcct aacaaagcct gcagtccaca ctccaaccct ggtgtctcac 6660
ctcctagcct ctcccaacat cctgctctct gaccatcttc tgcatctctc atctcaccat 6720
ctcccactgt ctacagccta ctcttgcaac taccatctca ttttctgaca tcctgtctac 6780
atcttctgcc atactctgcc atctaccata ccacctctta ccatctacca caccatcttt 6840
tatctccatc cctctcagaa gcctccaagc tgaatcctgc tttatgtgtt catctcagcc 6900
cctgcatgga aagctgaccc cagaggcaga actattccca gagagcttgg ccaagaaaaa 6960
caaaactacc agcctggcca ggctcaggag tagtaagctg cagtgtctgt tgtgttctag 7020
cttcaacagc tgcaggagtt ccactctcaa atgctccaca tttctcacat cctcctgatt 7080
ctggtcacta cccatcttca aagaacagaa tatctcacat cagcatactg tgaaggacta 7140
gtcatgggtg cagctgctca gagctgcaaa gtcattctgg atggtggaga gcttacaaac 7200
atttcatgat gctccccccg ctctgatggc tggagcccaa tccctacaca gactcctgct 7260
gtatgtgttt tcctttcact ctgagccaca gccagagggc aggcattcag tctcctcttc 7320
aggctggggc tggggcactg agaactcacc caacaccttg ctctcactcc ttctgcaaaa 7380
caagaaagag ctttgtgctg cagtagccat gaagaatgaa aggaaggctt taactaaaaa 7440
atgtcagaga ttattttcaa ccccttactg tggatcacca gcaaggagga aacacaacac 7500
agagacattt tttcccctca aattatcaaa agaatcactg catttgttaa agagagcaac 7560
tgaatcagga agcagagttt tgaacatatc agaagttagg aatctgcatc agagacaaat 7620
gcagtcatgg ttgtttgctg cataccagcc ctaatcatta gaagcctcat ggacttcaaa 7680
catcattccc tctgacaaga tgctctagcc taactccatg agataaaata aatctgcctt 7740
tcagagccaa agaagagtcc accagcttct tctcagtgtg aacaagagct ccagtcaggt 7800
tagtcagtcc agtgcagtag aggagaccag tctgcatcct ctaattttca aaggcaagaa 7860
gatttgttta ccctggacac caggcacaag tgaggtcaca gagctcttag atatgcagtc 7920
ctcatgagtg aggagactaa agcgcatgcc atcaagactt cagtgtagag aaaacctcca 7980
aaaaagcctc ctcactactt ctggaatagc tcagaggccg aggcggcctc ggcctctgca 8040
taaataaaaa aaattagtca gccatggggc ggagaatggg cggaactggg cggagttagg 8100
ggcgggatgg gcggagttag gggcgggact atggttgctg actaattgag atgcatgctt 8160
tgcatacttc tgcctgctgg ggagcctggg gactttccac acctggttgc tgactaattg 8220
agatgcatgc tttgcatact tctgcctgct ggggagcctg gggactttcc acaccctaac 8280
tgacacacat tccacagctg cattaatgaa tcggccaacg cgcggggaga ggcggtttgc 8340
gtattgggcg ctcttccgct tcctcgctca ctgactcgct gcgctcggtc gttcggctgc 8400
ggcgagcggt atcagctcac tcaaaggcgg taatacggtt atccacagaa tcaggggata 8460
acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc caggaaccgt aaaaaggccg 8520
cgttgctggc gtttttccat aggctccgcc cccctgacga gcatcacaaa aatcgacgct 8580
caagtcagag gtggcgaaac ccgacaggac tataaagata ccaggcgttt ccccctggaa 8640
gctccctcgt gcgctctcct gttccgaccc tgccgcttac cggatacctg tccgcctttc 8700
tcccttcggg aagcgtggcg ctttctcata gctcacgctg taggtatctc agttcggtgt 8760
aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc cgttcagccc gaccgctgcg 8820
ccttatccgg taactatcgt cttgagtcca acccggtaag acacgactta tcgccactgg 8880
cagcagccac tggtaacagg attagcagag cgaggtatgt aggcggtgct acagagttct 8940
tgaagtggtg gcctaactac ggctacacta gaagaacagt atttggtatc tgcgctctgc 9000
tgaagccagt taccttcgga aaaagagttg gtagctcttg atccggcaaa caaaccaccg 9060
ctggtagcgg tggttttttt gtttgcaagc agcagattac gcgcagaaaa aaaggatctc 9120
aagaagatcc tttgatcttt tctacggggt ctgacgctca gtggaacgaa aactcacgtt 9180
aagggatttt ggtcatgaga ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa 9240
aatgaagttt taaatcaatc taaagtatat atgagtaaac ttggtctgac agttaccaat 9300
gcttaatcag tgaggcacct atctcagcga tctgtctatt tcgttcatcc atagttgcct 9360
gactcctgca aaccacgttg tgtctcaaaa tctctgatgt tacattgcac aagataaaaa 9420
tatatcatca tgaacaataa aactgtctgc ttacataaac agtaatacaa ggggtgttat 9480
gagccatatt caacgggaaa cgtcttgctc gaggccgcga ttaaattcca acatggatgc 9540
tgatttatat gggtataaat gggctcgcga taatgtcggg caatcaggtg cgacaatcta 9600
tcgattgtat gggaagcccg atgcgccaga gttgtttctg aaacatggca aaggtagcgt 9660
tgccaatgat gttacagatg agatggtcag actaaactgg ctgacggaat ttatgcctct 9720
tccgaccatc aagcatttta tccgtactcc tgatgatgca tggttactca ccactgcgat 9780
ccccgggaaa acagcattcc aggtattaga agaatatcct gattcaggtg aaaatattgt 9840
tgatgcgctg gcagtgttcc tgcgccggtt gcattcgatt cctgtttgta attgtccttt 9900
taacagcgat cgcgtatttc gtctcgctca ggcgcaatca cgaatgaata acggtttggt 9960
tgatgcgagt gattttgatg acgagcgtaa tggctggcct gttgaacaag tctggaaaga 10020
aatgcataag cttttgccat tctcaccgga ttcagtcgtc actcatggtg atttctcact 10080
tgataacctt atttttgacg aggggaaatt aataggttgt attgatgttg gacgagtcgg 10140
aatcgcagac cgataccagg atcttgccat cctatggaac tgcctcggtg agttttctcc 10200
ttcattacag aaacggcttt ttcaaaaata tggtattgat aatcctgata tgaataaatt 10260
gcagtttcat ttgatgctcg atgagttttt ctaagggcgg cctgccacca tacccacgcc 10320
gaaacaagcg ctcatgagcc cgaagtggcg agcccgatct tccccatcgg tgatgtcggc 10380
gatataggcg ccagcaaccg cacctgtggc gccggtgatg agggcgcgcc aagtcgacgt 10440
ccggcagtct tggccactcc ctctctgcgc gctcgctcgc tcactgaggc cgggcgacca 10500
aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg agcgcgcaga 10560
gagggagtgg ccaactccat cactaggggt tcctgctagc tctgggtatt taagcccgag 10620
tgagcacgca gggtctccat tttgaagcgg gaggttacgc gttcgtcgac tactagtggg 10680
taccagagcg tggtgactga gatgttttct aggaaacaca aaagatacaa aaaagaacac 10740
gtggaaggat agccaaaaag gggggctgcc cccatttcct gcaccccgct gcgatggctg 10800
gcaccatttg gaagacttcg agatacactg ttgagcgcag taagacaaca gtgtatctcg 10860
aagtcttcca gatggggcca gccggtccac tctgtatcca ggccagttct gcaaggcgtt 10920
cgaggaccac ccccctcccc tcgccaccag ggtggtctca tacagaactt ataagattcc 10980
caaatccaaa gacatttcac gtttatggtg atttcccaga acacatagcg acatgcaaat 11040
attgcagggc gccactcccc tgtccctcac agccatcttc ctgccagggc gcacgcgcgc 11100
tgggtgttcc cgcctagtga cactgggccc gcgattcctt ggagcgggtt gatgacgtca 11160
gcgtttccca tggtgaatcc ctaggtt 11187
<210> 33
<211> 10996
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 33
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtccta gtaggcgaag ggtatcaaga ctacgaacac 300
ccatctgtgg ctttacagta ttcgtagtct tgatacccta cgctcactcg aggtggtctc 360
atacagaact tataagattc ccaaatccaa agacatttca cgtttatggt gatttcccag 420
aacacatagc gacatgcaaa tattgcaggg cgccactccc ctgtccctca cagccatctt 480
cctgccaggg cgcacgcgcg ctgggtgttc ccgcctagtg acactgggcc cgcgattcct 540
tggagcgggt tgatgacgtc agcgtttccc atggtgaagc ttggatctga attcggtacc 600
ctagttatta atagtaatca attacggggt cattagttca tagcccatat atggagttcc 660
gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat 720
tgacgtcaat aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc 780
aatgggtgga ctatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc 840
caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt 900
acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta 960
ccatggtcga ggtgagcccc acgttctgct tcactctccc catctccccc ccctccccac 1020
ccccaatttt gtatttattt attttttaat tattttgtgc agcgatgggg gcgggggggg 1080
ggggggggcg cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga 1140
gaggtgcggc ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc 1200
ggcggcggcg gcggccctat aaaaagcgaa gcgcgcggcg ggcgggagtc gctgcgacgc 1260
tgccttcgcc ccgtgccccg ctccgccgcc gcctcgcgcc gcccgccccg gctctgactg 1320
accgcgttac tcccacaggt gagcgggcgg gacggccctt ctcctccggg ctgtaattag 1380
cgcttggttt aatgacggct tgttttctgt ggctgcgtga aagccttgag gggctccggg 1440
agctagagcc tctgctaacc atgttcatgc cttcttcttt ttcctacagc tcctgggcaa 1500
cgtgctggtt attgtgctgt ctcatcattt tggcaaagaa ttcctcgaag atccgaaggg 1560
aaagtcttcc acgactgtgg gatccgttcg aagatatcac cggttgagcc accatggaat 1620
tcagcagccc cagcagagag gaatgcccca agcctctgag ccgggtgtca atcatggccg 1680
gatctctgac aggactgctg ctgcttcagg ccgtgtcttg ggcttctggc gctagacctt 1740
gcatccccaa gagcttcggc tacagcagcg tcgtgtgcgt gtgcaatgcc acctactgcg 1800
acagcttcga ccctcctacc tttcctgctc tgggcacctt cagcagatac gagagcacca 1860
gatccggcag acggatggaa ctgagcatgg gacccatcca ggccaatcac acaggcactg 1920
gcctgctgct gacactgcag cctgagcaga aattccagaa agtgaaaggc ttcggcggag 1980
ccatgacaga tgccgccgct ctgaatatcc tggctctgtc tccaccagct cagaacctgc 2040
tgctcaagag ctacttcagc gaggaaggca tcggctacaa catcatcaga gtgcccatgg 2100
ccagctgcga cttcagcatc aggacctaca cctacgccga cacacccgac gatttccagc 2160
tgcacaactt cagcctgcct gaagaggaca ccaagctgaa gatccctctg atccacagag 2220
ccctgcagct ggcacaaaga cccgtgtcac tgctggcctc tccatggaca tctcccacct 2280
ggctgaaaac aaatggcgcc gtgaatggca agggcagcct gaaaggccaa cctggcgaca 2340
tctaccacca gacctgggcc agatacttcg tgaagttcct ggacgcctat gccgagcaca 2400
agctgcagtt ttgggccgtg acagccgaga acgaaccttc tgctggactg ctgagcggct 2460
acccctttca gtgcctgggc tttacacccg agcaccagcg ggactttatc gcccgtgatc 2520
tgggacccac actggccaat agcacccacc ataatgtgcg gctgctgatg ctggacgacc 2580
agagactgct tctgccccac tgggctaaag tggtgctgac agatcctgag gccgccaaat 2640
acgtgcacgg aatcgccgtg cactggtatc tggactttct ggcccctgcc aaggccacac 2700
tgggagagac acacagactg ttccccaaca ccatgctgtt cgccagcgaa gcctgtgtgg 2760
gcagcaagtt ttgggaacag agcgtgcggc tcggcagctg ggatagaggc atgcagtaca 2820
gccacagcat catcaccaac ctgctgtacc acgtcgtcgg ctggaccgac tggaatctgg 2880
ccctgaatcc tgaaggcggc cctaactggg tccgaaactt cgtggacagc cccatcatcg 2940
tggacatcac caaggacacc ttctacaagc agcccatgtt ctaccacctg ggacacttca 3000
gcaagttcat ccccgagggc tctcagcgcg ttggactggt ggcttcccag aagaacgatc 3060
tggacgccgt ggctctgatg caccctgatg gatctgctgt ggtggtggtc ctgaaccgca 3120
gcagcaaaga tgtgcccctg accatcaagg atcccgccgt gggattcctg gaaacaatca 3180
gccctggcta ctccatccac acctacctgt ggcgtagaca gtgacaattg ttaattaagt 3240
ttaaaccctc gaggccgcaa gcttatcgat aatcaacctc tggattacaa aatttgtgaa 3300
agattgactg gtattcttaa ctatgttgct ccttttacgc tatgtggata cgctgcttta 3360
atgcctttgt atcatgctat tgcttcccgt atggctttca ttttctcctc cttgtataaa 3420
tcctggttgc tgtctcttta tgaggagttg tggcccgttg tcaggcaacg tggcgtggtg 3480
tgcactgtgt ttgctgacgc aacccccact ggttggggca ttgccaccac ctgtcagctc 3540
ctttccggga ctttcgcttt ccccctccct attgccacgg cggaactcat cgccgcctgc 3600
cttgcccgct gctggacagg ggctcggctg ttgggcactg acaattccgt ggtgttgtcg 3660
gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg ccacctggat tctgcgcggg 3720
acgtccttct gctacgtccc ttcggccctc aatccagcgg accttccttc ccgcggcctg 3780
ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc ctcagacgag tcggatctcc 3840
ctttgggccg cctccccgca tcgataccgt cgactagagc tcgctgatca gcctcgactg 3900
tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg 3960
aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga 4020
gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg 4080
aagacaatag caggcatgct ggggagagat ccacgataac aaacagcttt tttggggtga 4140
acatattgac tgaattccct gcaggttggc cactccctct ctgcgcgctc gctcgctcac 4200
tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt ggtcgcccgg cctcagtgag 4260
cgagcgagcg cgcagagagg gagtggccaa ctccatcact aggggttcct gcggccgctc 4320
gtacggtctc gaggaattcc tgcaggataa cttgccaacc tcattctaaa atgtatatag 4380
aagcccaaaa gacaataaca aaaatattct tgtagaacaa aatgggaaag aatgttccac 4440
taaatatcaa gatttagagc aaagcatgag atgtgtgggg atagacagtg aggctgataa 4500
aatagagtag agctcagaaa cagacccatt gatatatgta agtgacctat gaaaaaaata 4560
tggcatttta caatgggaaa atgatggtct ttttcttttt tagaaaaaca gggaaatata 4620
tttatatgta aaaaataaaa gggaacccat atgtcatacc atacacacaa aaaaattcca 4680
gtgaattata agtctaaatg gagaaggcaa aactttaaat cttttagaaa ataatataga 4740
agcatgcaga ccagcctggc caacatgatg aaaccctctc tactaataat aaaatcagta 4800
gaactactca ggactacttt gagtgggaag tccttttcta tgaagacttc tttggccaaa 4860
attaggctct aaatgcaagg agatagtgca tcatgcctgg ctgcacttac tgataaatga 4920
tgttatcacc atctttaacc aaatgcacag gaacaagtta tggtactgat gtgctggatt 4980
gagaaggagc tctacttcct tgacaggaca catttgtatc aacttaaaaa agcagatttt 5040
tgccagcaga actattcatt cagaggtagg aaacttagaa tagatgatgt cactgattag 5100
catggcttcc ccatctccac agctgcttcc cacccaggtt gcccacagtt gagtttgtcc 5160
agtgctcagg gctgcccact ctcagtaaga agccccacac cagcccctct ccaaatatgt 5220
tggctgttcc ttccattaaa gtgaccccac tttagagcag caagtggatt tctgtttctt 5280
acagttcagg aaggaggagt cagctgtgag aacctggagc ctgagatgct tctaagtccc 5340
actgctactg gggtcaggga agccagactc cagcatcagc agtcaggagc actaagccct 5400
tgccaacatc ctgtttctca gagaaactgc ttccattata atggttgtcc ttttttaagc 5460
tatcaagcca aacaaccagt gtctaccatt attctcatca cctgaagcca agggttctag 5520
caaaagtcaa gctgtcttgt aatggttgat gtgcctccag cttctgtctt cagtcactcc 5580
actcttagcc tgctctgaat caactctgac cacagttccc tggagcccct gccacctgct 5640
gcccctgcca ccttctccat ctgcagtgct gtgcagcctt ctgcactctt gcagagctaa 5700
taggtggaga cttgaaggaa gaggaggaaa gtttctcata atagccttgc tgcaagctca 5760
aatgggaggt gggcactgtg cccaggagcc ttggagcaaa ggctgtgccc aacctctgac 5820
tgcatccagg tttggtcttg acagagataa gaagccctgg cttttggagc caaaatctag 5880
gtcagactta ggcaggattc tcaaagttta tcagcagaac atgaggcaga agaccctttc 5940
tgctccagct tcttcaggct caaccttcat cagaatagat agaaagagag gctgtgaggg 6000
ttcttaaaac agaagcaaat ctgactcaga gaataaacaa cctcctagta aactacagct 6060
tagacagagc atctggtggt gagtgtgctc agtgtcctac tcaactgtct ggtatcagcc 6120
ctcatgagga cttctcttct ttccctcata gacctccatc tctgttttcc ttagcctgca 6180
gaaatctgga tggctattca cagaatgcct gtgctttcag agttgcattt tttctctggt 6240
attctggttc aagcatttga aggtaggaaa ggttctccaa gtgcaagaaa gccagccctg 6300
agcctcaact gcctggctag tgtggtcagt aggatgcaaa ggctgttgaa tgccacaagg 6360
ccaaacttta acctgtgtac cacaagccta gcagcagagg cagctctgct cactggaact 6420
ctctgtcttc tttctcctga gccttttctt ttcctgagtt ttctagctct cctcaacctt 6480
acctctgccc tacccaggac aaacccaaga gccactgttt ctgtgatgtc ctctccagcc 6540
ctaattaggc atcatgactt cagcctgacc ttccatgctc agaagcagtg ctaatccact 6600
tcagatgagc tgctctatgc aacacaggca gagcctacaa acctttgcac cagagccctc 6660
cacatatcag tgtttgttca tactcacttc aacagcaaat gtgactgctg agattaagat 6720
tttacacaag atggtctgta atttcacagt tagttttatc ccattaggta tgaaagaatt 6780
agcataattc cccttaaaca tgaatgaatc ttagattttt taataaatag ttttggaagt 6840
aaagacagag acatcaggag cacaaggaat agcctgagag gacaaacaga acaagaaaga 6900
gtctggaaat acacaggatg ttcttggcct cctcaaagca agtgcaagca gatagtacca 6960
gcagccccag gctatcagag cccagtgaag agaagtacca tgaaagccac agctctaacc 7020
accctgttcc agagtgacag acagtcccca agacaagcca gcctgagcca gagagagaac 7080
tgcaagagaa agtttctaat ttaggttctg ttagattcag acaagtgcag gtcatcctct 7140
ctccacagct actcacctct ccagcctaac aaagcctgca gtccacactc caaccctggt 7200
gtctcacctc ctagcctctc ccaacatcct gctctctgac catcttctgc atctctcatc 7260
tcaccatctc ccactgtcta cagcctactc ttgcaactac catctcattt tctgacatcc 7320
tgtctacatc ttctgccata ctctgccatc taccatacca cctcttacca tctaccacac 7380
catcttttat ctccatccct ctcagaagcc tccaagctga atcctgcttt atgtgttcat 7440
ctcagcccct gcatggaaag ctgaccccag aggcagaact attcccagag agcttggcca 7500
agaaaaacaa aactaccagc ctggccaggc tcaggagtag taagctgcag tgtctgttgt 7560
gttctagctt caacagctgc aggagttcca ctctcaaatg ctccacattt ctcacatcct 7620
cctgattctg gtcactaccc atcttcaaag aacagaatat ctcacatcag catactgtga 7680
aggactagtc atgggtgcag ctgctcagag ctgcaaagtc attctggatg gtggagagct 7740
tacaaacatt tcatgatgct ccccccgctc tgatggctgg agcccaatcc ctacacagac 7800
tcctgctgta tgtgttttcc tttcactctg agccacagcc agagggcagg cattcagtct 7860
cctcttcagg ctggggctgg ggcactgaga actcacccaa caccttgctc tcactccttc 7920
tgcaaaacaa gaaagagctt tgtgctgcag tagccatgaa gaatgaaagg aaggctttaa 7980
ctaaaaaatg tcagagatta ttttcaaccc cttactgtgg atcaccagca aggaggaaac 8040
acaacacaga gacatttttt cccctcaaat tatcaaaaga atcactgcat ttgttaaaga 8100
gagcaactga atcaggaagc agagttttga acatatcaga agttaggaat ctgcatcaga 8160
gacaaatgca gtcatggttg tttgctgcat accagcccta atcattagaa gcctcatgga 8220
cttcaaacat cattccctct gacaagatgc tctagcctaa ctccatgaga taaaataaat 8280
ctgcctttca gagccaaaga agagtccacc agcttcttct cagtgtgaac aagagctcca 8340
gtcaggttag tcagtccagt gcagtagagg agaccagtct gcatcctcta attttcaaag 8400
gcaagaagat ttgtttaccc tggacaccag gcacaagtga ggtcacagag ctcttagata 8460
tgcagtcctc atgagtgagg agactaaagc gcatgccatc aagacttcag tgtagagaaa 8520
acctccaaaa aagcctcctc actacttctg gaatagctca gaggccgagg cggcctcggc 8580
ctctgcataa ataaaaaaaa ttagtcagcc atggggcgga gaatgggcgg aactgggcgg 8640
agttaggggc gggatgggcg gagttagggg cgggactatg gttgctgact aattgagatg 8700
catgctttgc atacttctgc ctgctgggga gcctggggac tttccacacc tggttgctga 8760
ctaattgaga tgcatgcttt gcatacttct gcctgctggg gagcctgggg actttccaca 8820
ccctaactga cacacattcc acagctgcat taatgaatcg gccaacgcgc ggggagaggc 8880
ggtttgcgta ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg ctcggtcgtt 8940
cggctgcggc gagcggtatc agctcactca aaggcggtaa tacggttatc cacagaatca 9000
ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag gaaccgtaaa 9060
aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca tcacaaaaat 9120
cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca ggcgtttccc 9180
cctggaagct ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc 9240
gcctttctcc cttcgggaag cgtggcgctt tctcatagct cacgctgtag gtatctcagt 9300
tcggtgtagg tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt tcagcccgac 9360
cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc cggtaagaca cgacttatcg 9420
ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg cggtgctaca 9480
gagttcttga agtggtggcc taactacggc tacactagaa gaacagtatt tggtatctgc 9540
gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc cggcaaacaa 9600
accaccgctg gtagcggtgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa 9660
ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac 9720
tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta 9780
aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt 9840
taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg ttcatccata 9900
gttgcctgac tcctgcaaac cacgttgtgt ctcaaaatct ctgatgttac attgcacaag 9960
ataaaaatat atcatcatga acaataaaac tgtctgctta cataaacagt aatacaaggg 10020
gtgttatgag ccatattcaa cgggaaacgt cttgctcgag gccgcgatta aattccaaca 10080
tggatgctga tttatatggg tataaatggg ctcgcgataa tgtcgggcaa tcaggtgcga 10140
caatctatcg attgtatggg aagcccgatg cgccagagtt gtttctgaaa catggcaaag 10200
gtagcgttgc caatgatgtt acagatgaga tggtcagact aaactggctg acggaattta 10260
tgcctcttcc gaccatcaag cattttatcc gtactcctga tgatgcatgg ttactcacca 10320
ctgcgatccc cgggaaaaca gcattccagg tattagaaga atatcctgat tcaggtgaaa 10380
atattgttga tgcgctggca gtgttcctgc gccggttgca ttcgattcct gtttgtaatt 10440
gtccttttaa cagcgatcgc gtatttcgtc tcgctcaggc gcaatcacga atgaataacg 10500
gtttggttga tgcgagtgat tttgatgacg agcgtaatgg ctggcctgtt gaacaagtct 10560
ggaaagaaat gcataagctt ttgccattct caccggattc agtcgtcact catggtgatt 10620
tctcacttga taaccttatt tttgacgagg ggaaattaat aggttgtatt gatgttggac 10680
gagtcggaat cgcagaccga taccaggatc ttgccatcct atggaactgc ctcggtgagt 10740
tttctccttc attacagaaa cggctttttc aaaaatatgg tattgataat cctgatatga 10800
ataaattgca gtttcatttg atgctcgatg agtttttcta agggcggcct gccaccatac 10860
ccacgccgaa acaagcgctc atgagcccga agtggcgagc ccgatcttcc ccatcggtga 10920
tgtcggcgat ataggcgcca gcaaccgcac ctgtggcgcc ggtgatgagg gcgcgccaag 10980
tcgacgtccg gcagtc 10996
<210> 34
<211> 10845
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 34
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctccgg gctgtaatta 1080
gcgcttggtt taatgacggc ttgtctggag gcttgctttg ggctgtatgc tgtttagaaa 1140
taagtggtag tcattttggc ctctgactga tgactacact atttctaaac aggacacaag 1200
gccctttatc agcactcaca tggaacaaat ggccaccgtg ggaggatgac aatttctgtg 1260
gctgcgtgaa agccttgagg ggctccggga gctagagcct ctgctaacca tgttcatgcc 1320
ttcttctttt tcctacagct cctgggcaac gtgctggtta ttgtgctgtc tcatcatttt 1380
ggcaaagaat tcctcgaaga tccgaaggga aagtcttcca cgactgtggg atccgttcga 1440
agatatcacc ggttgagcca ccatggaatt cagcagcccc agcagagagg aatgccccaa 1500
gcctctgagc cgggtgtcaa tcatggccgg atctctgaca ggactgctgc tgcttcaggc 1560
cgtgtcttgg gcttctggcg ctagaccttg catccccaag agcttcggct acagcagcgt 1620
cgtgtgcgtg tgcaatgcca cctactgcga cagcttcgac cctcctacct ttcctgctct 1680
gggcaccttc agcagatacg agagcaccag atccggcaga cggatggaac tgagcatggg 1740
acccatccag gccaatcaca caggcactgg cctgctgctg acactgcagc ctgagcagaa 1800
attccagaaa gtgaaaggct tcggcggagc catgacagat gccgccgctc tgaatatcct 1860
ggctctgtct ccaccagctc agaacctgct gctcaagagc tacttcagcg aggaaggcat 1920
cggctacaac atcatcagag tgcccatggc cagctgcgac ttcagcatca ggacctacac 1980
ctacgccgac acacccgacg atttccagct gcacaacttc agcctgcctg aagaggacac 2040
caagctgaag atccctctga tccacagagc cctgcagctg gcacaaagac ccgtgtcact 2100
gctggcctct ccatggacat ctcccacctg gctgaaaaca aatggcgccg tgaatggcaa 2160
gggcagcctg aaaggccaac ctggcgacat ctaccaccag acctgggcca gatacttcgt 2220
gaagttcctg gacgcctatg ccgagcacaa gctgcagttt tgggccgtga cagccgagaa 2280
cgaaccttct gctggactgc tgagcggcta cccctttcag tgcctgggct ttacacccga 2340
gcaccagcgg gactttatcg cccgtgatct gggacccaca ctggccaata gcacccacca 2400
taatgtgcgg ctgctgatgc tggacgacca gagactgctt ctgccccact gggctaaagt 2460
ggtgctgaca gatcctgagg ccgccaaata cgtgcacgga atcgccgtgc actggtatct 2520
ggactttctg gcccctgcca aggccacact gggagagaca cacagactgt tccccaacac 2580
catgctgttc gccagcgaag cctgtgtggg cagcaagttt tgggaacaga gcgtgcggct 2640
cggcagctgg gatagaggca tgcagtacag ccacagcatc atcaccaacc tgctgtacca 2700
cgtcgtcggc tggaccgact ggaatctggc cctgaatcct gaaggcggcc ctaactgggt 2760
ccgaaacttc gtggacagcc ccatcatcgt ggacatcacc aaggacacct tctacaagca 2820
gcccatgttc taccacctgg gacacttcag caagttcatc cccgagggct ctcagcgcgt 2880
tggactggtg gcttcccaga agaacgatct ggacgccgtg gctctgatgc accctgatgg 2940
atctgctgtg gtggtggtcc tgaaccgcag cagcaaagat gtgcccctga ccatcaagga 3000
tcccgccgtg ggattcctgg aaacaatcag ccctggctac tccatccaca cctacctgtg 3060
gcgtagacag tgacaattgt taattaagtt taaaccctcg aggccgcaag cttatcgata 3120
atcaacctct ggattacaaa atttgtgaaa gattgactgg tattcttaac tatgttgctc 3180
cttttacgct atgtggatac gctgctttaa tgcctttgta tcatgctatt gcttcccgta 3240
tggctttcat tttctcctcc ttgtataaat cctggttgct gtctctttat gaggagttgt 3300
ggcccgttgt caggcaacgt ggcgtggtgt gcactgtgtt tgctgacgca acccccactg 3360
gttggggcat tgccaccacc tgtcagctcc tttccgggac tttcgctttc cccctcccta 3420
ttgccacggc ggaactcatc gccgcctgcc ttgcccgctg ctggacaggg gctcggctgt 3480
tgggcactga caattccgtg gtgttgtcgg ggaaatcatc gtcctttcct tggctgctcg 3540
cctgtgttgc cacctggatt ctgcgcggga cgtccttctg ctacgtccct tcggccctca 3600
atccagcgga ccttccttcc cgcggcctgc tgccggctct gcggcctctt ccgcgtcttc 3660
gccttcgccc tcagacgagt cggatctccc tttgggccgc ctccccgcat cgataccgtc 3720
gactagagct cgctgatcag cctcgactgt gccttctagt tgccagccat ctgttgtttg 3780
cccctccccc gtgccttcct tgaccctgga aggtgccact cccactgtcc tttcctaata 3840
aaatgaggaa attgcatcgc attgtctgag taggtgtcat tctattctgg ggggtggggt 3900
ggggcaggac agcaaggggg aggattggga agacaatagc aggcatgctg gggagagatc 3960
cacgataaca aacagctttt ttggggtgaa catattgact gaattccctg caggttggcc 4020
actccctctc tgcgcgctcg ctcgctcact gaggccgccc gggcaaagcc cgggcgtcgg 4080
gcgacctttg gtcgcccggc ctcagtgagc gagcgagcgc gcagagaggg agtggccaac 4140
tccatcacta ggggttcctg cggccgctcg tacggtctcg aggaattcct gcaggataac 4200
ttgccaacct cattctaaaa tgtatataga agcccaaaag acaataacaa aaatattctt 4260
gtagaacaaa atgggaaaga atgttccact aaatatcaag atttagagca aagcatgaga 4320
tgtgtgggga tagacagtga ggctgataaa atagagtaga gctcagaaac agacccattg 4380
atatatgtaa gtgacctatg aaaaaaatat ggcattttac aatgggaaaa tgatggtctt 4440
tttctttttt agaaaaacag ggaaatatat ttatatgtaa aaaataaaag ggaacccata 4500
tgtcatacca tacacacaaa aaaattccag tgaattataa gtctaaatgg agaaggcaaa 4560
actttaaatc ttttagaaaa taatatagaa gcatgcagac cagcctggcc aacatgatga 4620
aaccctctct actaataata aaatcagtag aactactcag gactactttg agtgggaagt 4680
ccttttctat gaagacttct ttggccaaaa ttaggctcta aatgcaagga gatagtgcat 4740
catgcctggc tgcacttact gataaatgat gttatcacca tctttaacca aatgcacagg 4800
aacaagttat ggtactgatg tgctggattg agaaggagct ctacttcctt gacaggacac 4860
atttgtatca acttaaaaaa gcagattttt gccagcagaa ctattcattc agaggtagga 4920
aacttagaat agatgatgtc actgattagc atggcttccc catctccaca gctgcttccc 4980
acccaggttg cccacagttg agtttgtcca gtgctcaggg ctgcccactc tcagtaagaa 5040
gccccacacc agcccctctc caaatatgtt ggctgttcct tccattaaag tgaccccact 5100
ttagagcagc aagtggattt ctgtttctta cagttcagga aggaggagtc agctgtgaga 5160
acctggagcc tgagatgctt ctaagtccca ctgctactgg ggtcagggaa gccagactcc 5220
agcatcagca gtcaggagca ctaagccctt gccaacatcc tgtttctcag agaaactgct 5280
tccattataa tggttgtcct tttttaagct atcaagccaa acaaccagtg tctaccatta 5340
ttctcatcac ctgaagccaa gggttctagc aaaagtcaag ctgtcttgta atggttgatg 5400
tgcctccagc ttctgtcttc agtcactcca ctcttagcct gctctgaatc aactctgacc 5460
acagttccct ggagcccctg ccacctgctg cccctgccac cttctccatc tgcagtgctg 5520
tgcagccttc tgcactcttg cagagctaat aggtggagac ttgaaggaag aggaggaaag 5580
tttctcataa tagccttgct gcaagctcaa atgggaggtg ggcactgtgc ccaggagcct 5640
tggagcaaag gctgtgccca acctctgact gcatccaggt ttggtcttga cagagataag 5700
aagccctggc ttttggagcc aaaatctagg tcagacttag gcaggattct caaagtttat 5760
cagcagaaca tgaggcagaa gaccctttct gctccagctt cttcaggctc aaccttcatc 5820
agaatagata gaaagagagg ctgtgagggt tcttaaaaca gaagcaaatc tgactcagag 5880
aataaacaac ctcctagtaa actacagctt agacagagca tctggtggtg agtgtgctca 5940
gtgtcctact caactgtctg gtatcagccc tcatgaggac ttctcttctt tccctcatag 6000
acctccatct ctgttttcct tagcctgcag aaatctggat ggctattcac agaatgcctg 6060
tgctttcaga gttgcatttt ttctctggta ttctggttca agcatttgaa ggtaggaaag 6120
gttctccaag tgcaagaaag ccagccctga gcctcaactg cctggctagt gtggtcagta 6180
ggatgcaaag gctgttgaat gccacaaggc caaactttaa cctgtgtacc acaagcctag 6240
cagcagaggc agctctgctc actggaactc tctgtcttct ttctcctgag ccttttcttt 6300
tcctgagttt tctagctctc ctcaacctta cctctgccct acccaggaca aacccaagag 6360
ccactgtttc tgtgatgtcc tctccagccc taattaggca tcatgacttc agcctgacct 6420
tccatgctca gaagcagtgc taatccactt cagatgagct gctctatgca acacaggcag 6480
agcctacaaa cctttgcacc agagccctcc acatatcagt gtttgttcat actcacttca 6540
acagcaaatg tgactgctga gattaagatt ttacacaaga tggtctgtaa tttcacagtt 6600
agttttatcc cattaggtat gaaagaatta gcataattcc ccttaaacat gaatgaatct 6660
tagatttttt aataaatagt tttggaagta aagacagaga catcaggagc acaaggaata 6720
gcctgagagg acaaacagaa caagaaagag tctggaaata cacaggatgt tcttggcctc 6780
ctcaaagcaa gtgcaagcag atagtaccag cagccccagg ctatcagagc ccagtgaaga 6840
gaagtaccat gaaagccaca gctctaacca ccctgttcca gagtgacaga cagtccccaa 6900
gacaagccag cctgagccag agagagaact gcaagagaaa gtttctaatt taggttctgt 6960
tagattcaga caagtgcagg tcatcctctc tccacagcta ctcacctctc cagcctaaca 7020
aagcctgcag tccacactcc aaccctggtg tctcacctcc tagcctctcc caacatcctg 7080
ctctctgacc atcttctgca tctctcatct caccatctcc cactgtctac agcctactct 7140
tgcaactacc atctcatttt ctgacatcct gtctacatct tctgccatac tctgccatct 7200
accataccac ctcttaccat ctaccacacc atcttttatc tccatccctc tcagaagcct 7260
ccaagctgaa tcctgcttta tgtgttcatc tcagcccctg catggaaagc tgaccccaga 7320
ggcagaacta ttcccagaga gcttggccaa gaaaaacaaa actaccagcc tggccaggct 7380
caggagtagt aagctgcagt gtctgttgtg ttctagcttc aacagctgca ggagttccac 7440
tctcaaatgc tccacatttc tcacatcctc ctgattctgg tcactaccca tcttcaaaga 7500
acagaatatc tcacatcagc atactgtgaa ggactagtca tgggtgcagc tgctcagagc 7560
tgcaaagtca ttctggatgg tggagagctt acaaacattt catgatgctc cccccgctct 7620
gatggctgga gcccaatccc tacacagact cctgctgtat gtgttttcct ttcactctga 7680
gccacagcca gagggcaggc attcagtctc ctcttcaggc tggggctggg gcactgagaa 7740
ctcacccaac accttgctct cactccttct gcaaaacaag aaagagcttt gtgctgcagt 7800
agccatgaag aatgaaagga aggctttaac taaaaaatgt cagagattat tttcaacccc 7860
ttactgtgga tcaccagcaa ggaggaaaca caacacagag acattttttc ccctcaaatt 7920
atcaaaagaa tcactgcatt tgttaaagag agcaactgaa tcaggaagca gagttttgaa 7980
catatcagaa gttaggaatc tgcatcagag acaaatgcag tcatggttgt ttgctgcata 8040
ccagccctaa tcattagaag cctcatggac ttcaaacatc attccctctg acaagatgct 8100
ctagcctaac tccatgagat aaaataaatc tgcctttcag agccaaagaa gagtccacca 8160
gcttcttctc agtgtgaaca agagctccag tcaggttagt cagtccagtg cagtagagga 8220
gaccagtctg catcctctaa ttttcaaagg caagaagatt tgtttaccct ggacaccagg 8280
cacaagtgag gtcacagagc tcttagatat gcagtcctca tgagtgagga gactaaagcg 8340
catgccatca agacttcagt gtagagaaaa cctccaaaaa agcctcctca ctacttctgg 8400
aatagctcag aggccgaggc ggcctcggcc tctgcataaa taaaaaaaat tagtcagcca 8460
tggggcggag aatgggcgga actgggcgga gttaggggcg ggatgggcgg agttaggggc 8520
gggactatgg ttgctgacta attgagatgc atgctttgca tacttctgcc tgctggggag 8580
cctggggact ttccacacct ggttgctgac taattgagat gcatgctttg catacttctg 8640
cctgctgggg agcctgggga ctttccacac cctaactgac acacattcca cagctgcatt 8700
aatgaatcgg ccaacgcgcg gggagaggcg gtttgcgtat tgggcgctct tccgcttcct 8760
cgctcactga ctcgctgcgc tcggtcgttc ggctgcggcg agcggtatca gctcactcaa 8820
aggcggtaat acggttatcc acagaatcag gggataacgc aggaaagaac atgtgagcaa 8880
aaggccagca aaaggccagg aaccgtaaaa aggccgcgtt gctggcgttt ttccataggc 8940
tccgcccccc tgacgagcat cacaaaaatc gacgctcaag tcagaggtgg cgaaacccga 9000
caggactata aagataccag gcgtttcccc ctggaagctc cctcgtgcgc tctcctgttc 9060
cgaccctgcc gcttaccgga tacctgtccg cctttctccc ttcgggaagc gtggcgcttt 9120
ctcatagctc acgctgtagg tatctcagtt cggtgtaggt cgttcgctcc aagctgggct 9180
gtgtgcacga accccccgtt cagcccgacc gctgcgcctt atccggtaac tatcgtcttg 9240
agtccaaccc ggtaagacac gacttatcgc cactggcagc agccactggt aacaggatta 9300
gcagagcgag gtatgtaggc ggtgctacag agttcttgaa gtggtggcct aactacggct 9360
acactagaag aacagtattt ggtatctgcg ctctgctgaa gccagttacc ttcggaaaaa 9420
gagttggtag ctcttgatcc ggcaaacaaa ccaccgctgg tagcggtggt ttttttgttt 9480
gcaagcagca gattacgcgc agaaaaaaag gatctcaaga agatcctttg atcttttcta 9540
cggggtctga cgctcagtgg aacgaaaact cacgttaagg gattttggtc atgagattat 9600
caaaaaggat cttcacctag atccttttaa attaaaaatg aagttttaaa tcaatctaaa 9660
gtatatatga gtaaacttgg tctgacagtt accaatgctt aatcagtgag gcacctatct 9720
cagcgatctg tctatttcgt tcatccatag ttgcctgact cctgcaaacc acgttgtgtc 9780
tcaaaatctc tgatgttaca ttgcacaaga taaaaatata tcatcatgaa caataaaact 9840
gtctgcttac ataaacagta atacaagggg tgttatgagc catattcaac gggaaacgtc 9900
ttgctcgagg ccgcgattaa attccaacat ggatgctgat ttatatgggt ataaatgggc 9960
tcgcgataat gtcgggcaat caggtgcgac aatctatcga ttgtatggga agcccgatgc 10020
gccagagttg tttctgaaac atggcaaagg tagcgttgcc aatgatgtta cagatgagat 10080
ggtcagacta aactggctga cggaatttat gcctcttccg accatcaagc attttatccg 10140
tactcctgat gatgcatggt tactcaccac tgcgatcccc gggaaaacag cattccaggt 10200
attagaagaa tatcctgatt caggtgaaaa tattgttgat gcgctggcag tgttcctgcg 10260
ccggttgcat tcgattcctg tttgtaattg tccttttaac agcgatcgcg tatttcgtct 10320
cgctcaggcg caatcacgaa tgaataacgg tttggttgat gcgagtgatt ttgatgacga 10380
gcgtaatggc tggcctgttg aacaagtctg gaaagaaatg cataagcttt tgccattctc 10440
accggattca gtcgtcactc atggtgattt ctcacttgat aaccttattt ttgacgaggg 10500
gaaattaata ggttgtattg atgttggacg agtcggaatc gcagaccgat accaggatct 10560
tgccatccta tggaactgcc tcggtgagtt ttctccttca ttacagaaac ggctttttca 10620
aaaatatggt attgataatc ctgatatgaa taaattgcag tttcatttga tgctcgatga 10680
gtttttctaa gggcggcctg ccaccatacc cacgccgaaa caagcgctca tgagcccgaa 10740
gtggcgagcc cgatcttccc catcggtgat gtcggcgata taggcgccag caaccgcacc 10800
tgtggcgccg gtgatgaggg cgcgccaagt cgacgtccgg cagtc 10845
<210> 35
<211> 11320
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 35
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg agggcggagt 300
tagggcggag ccaatcagcg tgcgccgttc cgaaagttgc cttttatggc tgggcggaga 360
atgggcggtg aacgccgatg attatataag gacgcgccgg gtgtggcaca gctagttccg 420
tcgcagccgg gatttgggtc gcggttcttg tttgtggatc cctgtgatcg tcacttggta 480
agtcactgac tgtctatgcc tgggaaaggg tgggcaggag atggggcagt gcaggaaaag 540
tggcactatg aaccctgtga tatcacaagg tcccagggct ggggtcagaa attctctccc 600
gagggaatga agccacagga gccaagagca ggaggaccaa ggccctggcg aaggccgtgg 660
cctcgttcaa gtaaaagatc ctagtacagt gcaggtccca atgtgtacta ggatctttta 720
cttgaacggg gacgccggca tccgggctca ggacccccct ctctgccaga ggcaccaaca 780
ccagagttca caaatcagtc tcctgccctt tgcatgtagc aaagcagccc taggaatgca 840
tctagacaat tgtactaacc ttcttctctt tcctctcctg acagtccgga aagccaccat 900
ggaattcagc agccccagca gagaggaatg ccccaagcct ctgagccggg tgtcaatcat 960
ggccggatct ctgacaggac tgctgctgct tcaggccgtg tcttgggctt ctggcgctag 1020
accttgcatc cccaagagct tcggctacag cagcgtcgtg tgcgtgtgca atgccaccta 1080
ctgcgacagc ttcgaccctc ctacctttcc tgctctgggc accttcagca gatacgagag 1140
caccagatcc ggcagacgga tggaactgag catgggaccc atccaggcca atcacacagg 1200
cactggcctg ctgctgacac tgcagcctga gcagaaattc cagaaagtga aaggcttcgg 1260
cggagccatg acagatgccg ccgctctgaa tatcctggct ctgtctccac cagctcagaa 1320
cctgctgctc aagagctact tcagcgagga aggcatcggc tacaacatca tcagagtgcc 1380
catggccagc tgcgacttca gcatcaggac ctacacctac gccgacacac ccgacgattt 1440
ccagctgcac aacttcagcc tgcctgaaga ggacaccaag ctgaagatcc ctctgatcca 1500
cagagccctg cagctggcac aaagacccgt gtcactgctg gcctctccat ggacatctcc 1560
cacctggctg aaaacaaatg gcgccgtgaa tggcaagggc agcctgaaag gccaacctgg 1620
cgacatctac caccagacct gggccagata cttcgtgaag ttcctggacg cctatgccga 1680
gcacaagctg cagttttggg ccgtgacagc cgagaacgaa ccttctgctg gactgctgag 1740
cggctacccc tttcagtgcc tgggctttac acccgagcac cagcgggact ttatcgcccg 1800
tgatctggga cccacactgg ccaatagcac ccaccataat gtgcggctgc tgatgctgga 1860
cgaccagaga ctgcttctgc cccactgggc taaagtggtg ctgacagatc ctgaggccgc 1920
caaatacgtg cacggaatcg ccgtgcactg gtatctggac tttctggccc ctgccaaggc 1980
cacactggga gagacacaca gactgttccc caacaccatg ctgttcgcca gcgaagcctg 2040
tgtgggcagc aagttttggg aacagagcgt gcggctcggc agctgggata gaggcatgca 2100
gtacagccac agcatcatca ccaacctgct gtaccacgtc gtcggctgga ccgactggaa 2160
tctggccctg aatcctgaag gcggccctaa ctgggtccga aacttcgtgg acagccccat 2220
catcgtggac atcaccaagg acaccttcta caagcagccc atgttctacc acctgggaca 2280
cttcagcaag ttcatccccg agggctctca gcgcgttgga ctggtggctt cccagaagaa 2340
cgatctggac gccgtggctc tgatgcaccc tgatggatct gctgtggtgg tggtcctgaa 2400
ccgcagcagc aaagatgtgc ccctgaccat caaggatccc gccgtgggat tcctggaaac 2460
aatcagccct ggctactcca tccacaccta cctgtggcgt agacaggagg gcagaggaag 2520
tcttctgaca tgcggagacg tggaagagaa tcccggccct atgtggaccc tggtgagctg 2580
ggtggccctg accgccggcc tggtggccgg cacccgctgc cccgacggcc agttctgccc 2640
cgtggcctgc tgcctggacc ccggcggcgc cagctacagc tgctgccgcc ccctgctgga 2700
caagtggccc accaccctga gccgccacct gggcggcccc tgccaggtgg acgcccactg 2760
cagcgccggc cacagctgca tcttcaccgt gagcggcacc agcagctgct gccccttccc 2820
cgaggccgtg gcctgcggcg acggccacca ctgctgcccc cgcggcttcc actgcagcgc 2880
cgacggccgc agctgcttcc agcgcagcgg caacaacagc gtgggcgcca tccagtgccc 2940
cgacagccag ttcgagtgcc ccgacttcag cacctgctgc gtgatggtgg acggcagctg 3000
gggctgctgc cccatgcccc aggccagctg ctgcgaggac cgcgtgcact gctgccccca 3060
cggcgccttc tgcgacctgg tgcacacccg ctgcatcacc cccaccggca cccaccccct 3120
ggccaagaag ctgcccgccc agcgcaccaa ccgcgccgtg gccctgagca gcagcgtgat 3180
gtgccccgac gcccgcagcc gctgccccga cggcagcacc tgctgcgagc tgcccagcgg 3240
caagtacggc tgctgcccca tgcccaacgc cacctgctgc agcgaccacc tgcactgctg 3300
cccccaggac accgtgtgcg acctgatcca gagcaagtgc ctgagcaagg agaacgccac 3360
caccgacctg ctgaccaagc tgcccgccca caccgtgggc gacgtgaagt gcgacatgga 3420
ggtgagctgc cccgacggct acacctgctg ccgcctgcag agcggcgcct ggggctgctg 3480
ccccttcacc caggccgtgt gctgcgagga ccacatccac tgctgccccg ccggcttcac 3540
ctgcgacacc cagaagggca cctgcgagca gggcccccac caggtgccct ggatggagaa 3600
ggcccccgcc cacctgagcc tgcccgaccc ccaggccctg aagcgcgacg tgccctgcga 3660
caacgtgagc agctgcccca gcagcgacac ctgctgccag ctgaccagcg gcgagtgggg 3720
ctgctgcccc atccccgagg ccgtgtgctg cagcgaccac cagcactgct gcccccaggg 3780
ctacacctgc gtggccgagg gccagtgcca gcgcggcagc gagatcgtgg ccggcctgga 3840
gaagatgccc gcccgccgcg ccagcctgag ccacccccgc gacatcggct gcgaccagca 3900
caccagctgc cccgtgggcc agacctgctg ccccagcctg ggcggcagct gggcctgctg 3960
ccagctgccc cacgccgtgt gctgcgagga ccgccagcac tgctgccccg ccggctacac 4020
ctgcaacgtg aaggcccgca gctgcgagaa ggaggtggtg agcgcccagc ccgccacctt 4080
cctggcccgc agcccccacg tgggcgtgaa ggacgtggag tgcggcgagg gccacttctg 4140
ccacgacaac cagacctgct gccgcgacaa ccgccagggc tgggcctgct gcccctaccg 4200
ccagggcgtg tgctgcgccg accgccgcca ctgctgcccc gccggcttcc gctgcgccgc 4260
ccgcggcacc aagtgcctgc gccgcgaggc cccccgctgg gacgcccccc tgcgcgaccc 4320
cgccctgcgc cagctgctgt gacaattgtt aattaagttt aaaccctcga ggccgcaagc 4380
aataaaatat ctttattttc attacatctg tgtgttggtt ttttgtgtgg agatccacga 4440
taacaaacag cttttttggg gtgaacatat tgactgaatt ccctgcaggt tggccactcc 4500
ctctctgcgc gctcgctcgc tcactgaggc cgcccgggca aagcccgggc gtcgggcgac 4560
ctttggtcgc ccggcctcag tgagcgagcg agcgcgcaga gagggagtgg ccaactccat 4620
cactaggggt tcctgcggcc gctcgtacgg tctcgaggaa ttcctgcagg ataacttgcc 4680
aacctcattc taaaatgtat atagaagccc aaaagacaat aacaaaaata ttcttgtaga 4740
acaaaatggg aaagaatgtt ccactaaata tcaagattta gagcaaagca tgagatgtgt 4800
ggggatagac agtgaggctg ataaaataga gtagagctca gaaacagacc cattgatata 4860
tgtaagtgac ctatgaaaaa aatatggcat tttacaatgg gaaaatgatg gtctttttct 4920
tttttagaaa aacagggaaa tatatttata tgtaaaaaat aaaagggaac ccatatgtca 4980
taccatacac acaaaaaaat tccagtgaat tataagtcta aatggagaag gcaaaacttt 5040
aaatctttta gaaaataata tagaagcatg cagaccagcc tggccaacat gatgaaaccc 5100
tctctactaa taataaaatc agtagaacta ctcaggacta ctttgagtgg gaagtccttt 5160
tctatgaaga cttctttggc caaaattagg ctctaaatgc aaggagatag tgcatcatgc 5220
ctggctgcac ttactgataa atgatgttat caccatcttt aaccaaatgc acaggaacaa 5280
gttatggtac tgatgtgctg gattgagaag gagctctact tccttgacag gacacatttg 5340
tatcaactta aaaaagcaga tttttgccag cagaactatt cattcagagg taggaaactt 5400
agaatagatg atgtcactga ttagcatggc ttccccatct ccacagctgc ttcccaccca 5460
ggttgcccac agttgagttt gtccagtgct cagggctgcc cactctcagt aagaagcccc 5520
acaccagccc ctctccaaat atgttggctg ttccttccat taaagtgacc ccactttaga 5580
gcagcaagtg gatttctgtt tcttacagtt caggaaggag gagtcagctg tgagaacctg 5640
gagcctgaga tgcttctaag tcccactgct actggggtca gggaagccag actccagcat 5700
cagcagtcag gagcactaag cccttgccaa catcctgttt ctcagagaaa ctgcttccat 5760
tataatggtt gtcctttttt aagctatcaa gccaaacaac cagtgtctac cattattctc 5820
atcacctgaa gccaagggtt ctagcaaaag tcaagctgtc ttgtaatggt tgatgtgcct 5880
ccagcttctg tcttcagtca ctccactctt agcctgctct gaatcaactc tgaccacagt 5940
tccctggagc ccctgccacc tgctgcccct gccaccttct ccatctgcag tgctgtgcag 6000
ccttctgcac tcttgcagag ctaataggtg gagacttgaa ggaagaggag gaaagtttct 6060
cataatagcc ttgctgcaag ctcaaatggg aggtgggcac tgtgcccagg agccttggag 6120
caaaggctgt gcccaacctc tgactgcatc caggtttggt cttgacagag ataagaagcc 6180
ctggcttttg gagccaaaat ctaggtcaga cttaggcagg attctcaaag tttatcagca 6240
gaacatgagg cagaagaccc tttctgctcc agcttcttca ggctcaacct tcatcagaat 6300
agatagaaag agaggctgtg agggttctta aaacagaagc aaatctgact cagagaataa 6360
acaacctcct agtaaactac agcttagaca gagcatctgg tggtgagtgt gctcagtgtc 6420
ctactcaact gtctggtatc agccctcatg aggacttctc ttctttccct catagacctc 6480
catctctgtt ttccttagcc tgcagaaatc tggatggcta ttcacagaat gcctgtgctt 6540
tcagagttgc attttttctc tggtattctg gttcaagcat ttgaaggtag gaaaggttct 6600
ccaagtgcaa gaaagccagc cctgagcctc aactgcctgg ctagtgtggt cagtaggatg 6660
caaaggctgt tgaatgccac aaggccaaac tttaacctgt gtaccacaag cctagcagca 6720
gaggcagctc tgctcactgg aactctctgt cttctttctc ctgagccttt tcttttcctg 6780
agttttctag ctctcctcaa ccttacctct gccctaccca ggacaaaccc aagagccact 6840
gtttctgtga tgtcctctcc agccctaatt aggcatcatg acttcagcct gaccttccat 6900
gctcagaagc agtgctaatc cacttcagat gagctgctct atgcaacaca ggcagagcct 6960
acaaaccttt gcaccagagc cctccacata tcagtgtttg ttcatactca cttcaacagc 7020
aaatgtgact gctgagatta agattttaca caagatggtc tgtaatttca cagttagttt 7080
tatcccatta ggtatgaaag aattagcata attcccctta aacatgaatg aatcttagat 7140
tttttaataa atagttttgg aagtaaagac agagacatca ggagcacaag gaatagcctg 7200
agaggacaaa cagaacaaga aagagtctgg aaatacacag gatgttcttg gcctcctcaa 7260
agcaagtgca agcagatagt accagcagcc ccaggctatc agagcccagt gaagagaagt 7320
accatgaaag ccacagctct aaccaccctg ttccagagtg acagacagtc cccaagacaa 7380
gccagcctga gccagagaga gaactgcaag agaaagtttc taatttaggt tctgttagat 7440
tcagacaagt gcaggtcatc ctctctccac agctactcac ctctccagcc taacaaagcc 7500
tgcagtccac actccaaccc tggtgtctca cctcctagcc tctcccaaca tcctgctctc 7560
tgaccatctt ctgcatctct catctcacca tctcccactg tctacagcct actcttgcaa 7620
ctaccatctc attttctgac atcctgtcta catcttctgc catactctgc catctaccat 7680
accacctctt accatctacc acaccatctt ttatctccat ccctctcaga agcctccaag 7740
ctgaatcctg ctttatgtgt tcatctcagc ccctgcatgg aaagctgacc ccagaggcag 7800
aactattccc agagagcttg gccaagaaaa acaaaactac cagcctggcc aggctcagga 7860
gtagtaagct gcagtgtctg ttgtgttcta gcttcaacag ctgcaggagt tccactctca 7920
aatgctccac atttctcaca tcctcctgat tctggtcact acccatcttc aaagaacaga 7980
atatctcaca tcagcatact gtgaaggact agtcatgggt gcagctgctc agagctgcaa 8040
agtcattctg gatggtggag agcttacaaa catttcatga tgctcccccc gctctgatgg 8100
ctggagccca atccctacac agactcctgc tgtatgtgtt ttcctttcac tctgagccac 8160
agccagaggg caggcattca gtctcctctt caggctgggg ctggggcact gagaactcac 8220
ccaacacctt gctctcactc cttctgcaaa acaagaaaga gctttgtgct gcagtagcca 8280
tgaagaatga aaggaaggct ttaactaaaa aatgtcagag attattttca accccttact 8340
gtggatcacc agcaaggagg aaacacaaca cagagacatt ttttcccctc aaattatcaa 8400
aagaatcact gcatttgtta aagagagcaa ctgaatcagg aagcagagtt ttgaacatat 8460
cagaagttag gaatctgcat cagagacaaa tgcagtcatg gttgtttgct gcataccagc 8520
cctaatcatt agaagcctca tggacttcaa acatcattcc ctctgacaag atgctctagc 8580
ctaactccat gagataaaat aaatctgcct ttcagagcca aagaagagtc caccagcttc 8640
ttctcagtgt gaacaagagc tccagtcagg ttagtcagtc cagtgcagta gaggagacca 8700
gtctgcatcc tctaattttc aaaggcaaga agatttgttt accctggaca ccaggcacaa 8760
gtgaggtcac agagctctta gatatgcagt cctcatgagt gaggagacta aagcgcatgc 8820
catcaagact tcagtgtaga gaaaacctcc aaaaaagcct cctcactact tctggaatag 8880
ctcagaggcc gaggcggcct cggcctctgc ataaataaaa aaaattagtc agccatgggg 8940
cggagaatgg gcggaactgg gcggagttag gggcgggatg ggcggagtta ggggcgggac 9000
tatggttgct gactaattga gatgcatgct ttgcatactt ctgcctgctg gggagcctgg 9060
ggactttcca cacctggttg ctgactaatt gagatgcatg ctttgcatac ttctgcctgc 9120
tggggagcct ggggactttc cacaccctaa ctgacacaca ttccacagct gcattaatga 9180
atcggccaac gcgcggggag aggcggtttg cgtattgggc gctcttccgc ttcctcgctc 9240
actgactcgc tgcgctcggt cgttcggctg cggcgagcgg tatcagctca ctcaaaggcg 9300
gtaatacggt tatccacaga atcaggggat aacgcaggaa agaacatgtg agcaaaaggc 9360
cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg cgtttttcca taggctccgc 9420
ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga ggtggcgaaa cccgacagga 9480
ctataaagat accaggcgtt tccccctgga agctccctcg tgcgctctcc tgttccgacc 9540
ctgccgctta ccggatacct gtccgccttt ctcccttcgg gaagcgtggc gctttctcat 9600
agctcacgct gtaggtatct cagttcggtg taggtcgttc gctccaagct gggctgtgtg 9660
cacgaacccc ccgttcagcc cgaccgctgc gccttatccg gtaactatcg tcttgagtcc 9720
aacccggtaa gacacgactt atcgccactg gcagcagcca ctggtaacag gattagcaga 9780
gcgaggtatg taggcggtgc tacagagttc ttgaagtggt ggcctaacta cggctacact 9840
agaagaacag tatttggtat ctgcgctctg ctgaagccag ttaccttcgg aaaaagagtt 9900
ggtagctctt gatccggcaa acaaaccacc gctggtagcg gtggtttttt tgtttgcaag 9960
cagcagatta cgcgcagaaa aaaaggatct caagaagatc ctttgatctt ttctacgggg 10020
tctgacgctc agtggaacga aaactcacgt taagggattt tggtcatgag attatcaaaa 10080
aggatcttca cctagatcct tttaaattaa aaatgaagtt ttaaatcaat ctaaagtata 10140
tatgagtaaa cttggtctga cagttaccaa tgcttaatca gtgaggcacc tatctcagcg 10200
atctgtctat ttcgttcatc catagttgcc tgactcctgc aaaccacgtt gtgtctcaaa 10260
atctctgatg ttacattgca caagataaaa atatatcatc atgaacaata aaactgtctg 10320
cttacataaa cagtaataca aggggtgtta tgagccatat tcaacgggaa acgtcttgct 10380
cgaggccgcg attaaattcc aacatggatg ctgatttata tgggtataaa tgggctcgcg 10440
ataatgtcgg gcaatcaggt gcgacaatct atcgattgta tgggaagccc gatgcgccag 10500
agttgtttct gaaacatggc aaaggtagcg ttgccaatga tgttacagat gagatggtca 10560
gactaaactg gctgacggaa tttatgcctc ttccgaccat caagcatttt atccgtactc 10620
ctgatgatgc atggttactc accactgcga tccccgggaa aacagcattc caggtattag 10680
aagaatatcc tgattcaggt gaaaatattg ttgatgcgct ggcagtgttc ctgcgccggt 10740
tgcattcgat tcctgtttgt aattgtcctt ttaacagcga tcgcgtattt cgtctcgctc 10800
aggcgcaatc acgaatgaat aacggtttgg ttgatgcgag tgattttgat gacgagcgta 10860
atggctggcc tgttgaacaa gtctggaaag aaatgcataa gcttttgcca ttctcaccgg 10920
attcagtcgt cactcatggt gatttctcac ttgataacct tatttttgac gaggggaaat 10980
taataggttg tattgatgtt ggacgagtcg gaatcgcaga ccgataccag gatcttgcca 11040
tcctatggaa ctgcctcggt gagttttctc cttcattaca gaaacggctt tttcaaaaat 11100
atggtattga taatcctgat atgaataaat tgcagtttca tttgatgctc gatgagtttt 11160
tctaagggcg gcctgccacc atacccacgc cgaaacaagc gctcatgagc ccgaagtggc 11220
gagcccgatc ttccccatcg gtgatgtcgg cgatataggc gccagcaacc gcacctgtgg 11280
cgccggtgat gagggcgcgc caagtcgacg tccggcagtc 11320
<210> 36
<211> 3793
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 36
tctcattaga agtgaggcgg ggccggccaa atcgaatgga caccgggtaa ttagcagggt 60
tacccagata ctccagcacc tctttcccgt cggccgtgta cctgccattc acgtccatgc 120
cattgatggc cagcactgca tgacccactg cagaggtgaa gctaacggtc agcgaaggtg 180
cagcccgggg attccgccga ggggacaagg gacccgacac aacccctttt cccccaaccc 240
cgcacctaca accagcccac ttctacagca ctggggccct cccacccccg cacccgccac 300
gggcccgagc ctagcccacc tcggatgccg tcccgctggc cgaaagcaac caacacacgc 360
tcatcgtgta gcttgagcag cagatccagc ggataactga aagttttctc agcctcagcc 420
cgtggcgcgt agctgtccaa ctggtaaatc aagccgccag ctttgttcac cacatacaca 480
ctaaaaatcg ccatcgctgc cttgccgctc ggaaactggt attcagcctc tacccgacgg 540
cccctccccg gaaccgcatc acagcacttg ccgccggccc caccccagcc tcctcctcct 600
cctcctcctc ctcccgcgcc ccccgtgcag ccacctgctg cacttgcgca ctgggagcga 660
cacgctcggg cataagtagt gccgaaaagt tagctgccga gacctggtgg attgcttttc 720
gtttatcagt gcaggaaaac agcgctatag tactgcgtca caactagcgc agactccggc 780
agtatttagg cggtgcggct tgggaactag aatccacttc ctgtcttccg cctcaggcta 840
gagggcgagc gcttcgccgt gggacttctt ctgcctggct ccgcctcttg ccccggaagt 900
actcacagcg gacggtggtt tttgggcccg tttctgagca gcgcttcctt tttgtccgac 960
atcttgacga ggctgcggtg tctgctgcta ttctccgagc ttcgcaatgg taagcttcag 1020
gggtgtgaag tcgccggcgt tcttgggttt gaggactcag tggggagagc cttcggcggg 1080
agcgctcctt ggcctgccgg cctcggttgc agggcgggcg cggttattgc ttggcccatg 1140
tgctctggtg gtggagtttg cgggggctga gggcgcagta ttaggggact ttggcgctat 1200
ttgaggacct ggttgcattc ccgctgccct cctacagccg cctaaggacg acaagaagaa 1260
gaaggacgct ggaaagtcgg ccaagaaaga caaagaccca gtgaacaaat ccgggggcaa 1320
ggccaaaaag aaggtagaaa taagacctct ctgaaagaga ctaggggtaa ctctctcgta 1380
atcctctagt aataggtaac ttgtatagta agtggttttt caggtgtaga tttctagagt 1440
caaaatgtga gagtttatct tcccgtcacc actcgttctt tttcccatta ggatcatgaa 1500
aatgggtctg ttgtgcgaag tgtctgccgc tgtgcctgct gtgttatttt taactgatct 1560
agtggggctc ggcccctgtt tgaaggccaa aaacgtgtcg gtgttttttt tttgtttttg 1620
ttttagtaat gtgtaattta tccttgataa cggtggaaca gatttctctg acgcagatta 1680
ctcgagaggg aaagggtgct tctgccagaa atactaactt gtttctgttt tgttttggtg 1740
agcagaagtg gtccaaaggc aaagttcggg acaagctcaa taacttagtc ttgtttgaca 1800
aagctaccta tgataaactc tgtaaggaag ttcccaacta taaacttata accccagctg 1860
tggtctctga gagactgaag attcgaggct ccctggccag ggcagccctt caggagctcc 1920
ttagtaaagg tgaggggtgt atcctacatg tgtgtttttg taggttaaat tgtcttgacc 1980
atgttaagca tcttcagtgg ttttgctgga aaagcagaat taaaaaaaaa aagcgtggct 2040
tgaccattgg ctgttagtaa tgtaattctg acgtcttact cctgatcctg agatgaattc 2100
tcagggttct tagccacttt tgtgccgtgg accctgtggc agtttagtga agcccaagga 2160
tcttttatgt ttcgagtaaa tggatgcata gaattacagg gacaaccgtt tttgaaataa 2220
ttagattact attttgaaac aactttgaaa atgtttaaaa cctttatggt aaatattttg 2280
ttgatgtatt aaattttaaa accagaaatt tagtacggtc tactcagtag tatggtctga 2340
ttaccataat tccacaataa taaggctcag ctaactatag tgactgaacg tctataattc 2400
tagcactttg ggaggccaag gcgggtgaat caacggaggt caggagttaa agaccagcct 2460
ggccaatatg gtgaaaacct gctctactga aagttagctg gacgtggggg cacacgtctg 2520
taatcccagc tactcaggat gctgaggcat gaggatccct tgaacccagg agatggaggt 2580
ggcagtgagc cgagatgaca ccactgcact ccagccttag tgacagcaaa agactgtctc 2640
agaaaggggg ggggggtgga agataatgga gccctaattt aaaggaaaag taaggataga 2700
tgatccgtta aaaacttgga ttctcggtta ccgaacgtca gattaagcaa ttctggagcc 2760
aggtgcagtg gtacccttgt atttctagct acttgggagg ccaaagcagg aggatcattt 2820
gagccaagga gttttaagac cattctgggc acctctgaga gaactctgtc tttttgtttt 2880
ccttttcttt aaatagagat gcggttttgc catgttgccc aggctggtct cctgggctca 2940
agagatccac ctgtccaaag tgctgggatt acaggcatga gcctctgcac ccggccaaaa 3000
caaaccttac tagagtctca ttctgttgcc caggttggag tgcggagggg cagtcttggc 3060
tcaatgcaac caccaattcc tgggttcagg tggtcctcac ctcagcttcc caagtagctg 3120
gaattacaag catgtgccac catgcccagc taatttttgt atttttggta gagatggggt 3180
ttcaccttgt tggccaggct ggtgtgcaac tccttacctc aagctatctg cccgtctcca 3240
cctcccaaag cagtgggatt ataagcatga gccaccgcgc ccagccaaaa accttactag 3300
tttctattgt agcatctgtt aagcatctca tcgtgctatt ctctccccct aggacttatc 3360
aaactggttt caaagcacag agctcaagta atttacacca gaaataccaa gggtggagat 3420
gctccagctg ctggtgaaga tgcatgaata ggtgagtagg aatgtgtggg ctcatggtgt 3480
aggaggtaga tacaaagctt tatggttctg attcttttaa ttttttttta caggtccaac 3540
cagctgtaca tttggaaaaa taaaacttta ttaaatcaaa tgaatgagta tgtctgtttc 3600
ctaagaaaga caatgataaa gaatttggtg gaaggtataa taggggtttg ttgactttgc 3660
ttttagcctc atggtagttg gtagagagca tgattagctt ttttctgtat gtgactgctt 3720
cttcattgct gcagcttcag ttttgaattg atgtctgaaa ggaaataaag ggttaacacg 3780
atgatgaagg gtg 3793
<210> 37
<211> 6762
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 37
ggacggccga gcggcagggc gctcgcgcgc gcccactagt ggccggagga gaaggctccc 60
gcggaggccg cgctgcccgc cccctcccct ggggaggctc gcgttcccgc tgctcgcgcc 120
tgcgccgccc gccggcctca ggaacgcgcc ctcttcgccg gcgcgcgccc tcgcagtcac 180
cgccacccac cagctccggc accaacagca gcgccgctgc caccgcccac cttctgccgc 240
cgccaccaca gccaccttct cctcctccgc tgtcctctcc cgtcctcgcc tctgtcgact 300
atcaggtgaa ctttgaacca ggatggctga gccccgccag gagttcgaag tgatggaaga 360
tcacgctggg acgtacgggt tgggggacag gaaagatcag gggggctaca ccatgcacca 420
agaccaagag ggtgacacgg acgctggcct gaaagaatct cccctgcaga cccccactga 480
ggacggatct gaggaaccgg gctctgaaac ctctgatgct aagagcactc caacagcgga 540
agatgtgaca gcacccttag tggatgaggg agctcccggc aagcaggctg ccgcgcagcc 600
ccacacggag atcccagaag gaaccacagc tgaagaagca ggcattggag acacccccag 660
cctggaagac gaagctgctg gtcacgtgac ccaagagcct gaaagtggta aggtggtcca 720
ggaaggcttc ctccgagagc caggcccccc aggtctgagc caccagctca tgtccggcat 780
gcctggggct cccctcctgc ctgagggccc cagagaggcc acacgccaac cttcggggac 840
aggacctgag gacacagagg gcggccgcca cgcccctgag ctgctcaagc accagcttct 900
aggagacctg caccaggagg ggccgccgct gaagggggca gggggcaaag agaggccggg 960
gagcaaggag gaggtggatg aagaccgcga cgtcgatgag tcctcccccc aagactcccc 1020
tccctccaag gcctccccag cccaagatgg gcggcctccc cagacagccg ccagagaagc 1080
caccagcatc ccaggcttcc cagcggaggg tgccatcccc ctccctgtgg atttcctctc 1140
caaagtttcc acagagatcc cagcctcaga gcccgacggg cccagtgtag ggcgggccaa 1200
agggcaggat gcccccctgg agttcacgtt tcacgtggaa atcacaccca acgtgcagaa 1260
ggagcaggcg cactcggagg agcatttggg aagggctgca tttccagggg cccctggaga 1320
ggggccagag gcccggggcc cctctttggg agaggacaca aaagaggctg accttccaga 1380
gccctctgaa aagcagcctg ctgctgctcc gcgggggaag cccgtcagcc gggtccctca 1440
actcaaagct cgcatggtca gtaaaagcaa agacgggact ggaagcgatg acaaaaaagc 1500
caagacatcc acacgttcct ctgctaaaac cttgaaaaat aggccttgcc ttagccccaa 1560
acaccccact cctggtagct cagaccctct gatccaaccc tccagccctg ctgtgtgccc 1620
agagccacct tcctctccta aatacgtctc ttctgtcact tcccgaactg gcagttctgg 1680
agcaaaggag atgaaactca agggggctga tggtaaaacg aagatcgcca caccgcgggg 1740
agcagcccct ccaggccaga agggccaggc caacgccacc aggattccag caaaaacccc 1800
gcccgctcca aagacaccac ccagctctgg tgaacctcca aaatcagggg atcgcagcgg 1860
ctacagcagc cccggctccc caggcactcc cggcagccgc tcccgcaccc cgtcccttcc 1920
aaccccaccc acccgggagc ccaagaaggt ggcagtggtc cgtactccac ccaagtcgcc 1980
gtcttccgcc aagagccgcc tgcagacagc ccccgtgccc atgccagacc tgaagaatgt 2040
caagtccaag atcggctcca ctgagaacct gaagcaccag ccgggaggcg ggaaggtgca 2100
gataattaat aagaagctgg atcttagcaa cgtccagtcc aagtgtggct caaaggataa 2160
tatcaaacac gtcccgggag gcggcagtgt gcaaatagtc tacaaaccag ttgacctgag 2220
caaggtgacc tccaagtgtg gctcattagg caacatccat cataaaccag gaggtggcca 2280
ggtggaagta aaatctgaga agcttgactt caaggacaga gtccagtcga agattgggtc 2340
cctggacaat atcacccacg tccctggcgg aggaaataaa aagattgaaa cccacaagct 2400
gaccttccgc gagaacgcca aagccaagac agaccacggg gcggagatcg tgtacaagtc 2460
gccagtggtg tctggggaca cgtctccacg gcatctcagc aatgtctcct ccaccggcag 2520
catcgacatg gtagactcgc cccagctcgc cacgctagct gacgaggtgt ctgcctccct 2580
ggccaagcag ggtttgtgat caggcccctg gggcggtcaa taattgtgga gaggagagaa 2640
tgagagagtg tggaaaaaaa aagaataatg acccggcccc cgccctctgc ccccagctgc 2700
tcctcgcagt tcggttaatt ggttaatcac ttaacctgct tttgtcactc ggctttggct 2760
cgggacttca aaatcagtga tgggagtaag agcaaatttc atctttccaa attgatgggt 2820
gggctagtaa taaaatattt aaaaaaaaac attcaaaaac atggccacat ccaacatttc 2880
ctcaggcaat tccttttgat tcttttttct tccccctcca tgtagaagag ggagaaggag 2940
aggctctgaa agctgcttct gggggatttc aagggactgg gggtgccaac cacctctggc 3000
cctgttgtgg gggtgtcaca gaggcagtgg cagcaacaaa ggatttgaaa cttggtgtgt 3060
tcgtggagcc acaggcagac gatgtcaacc ttgtgtgagt gtgacggggg ttggggtggg 3120
gcgggaggcc acgggggagg ccgaggcagg ggctgggcag aggggagagg aagcacaaga 3180
agtgggagtg ggagaggaag ccacgtgctg gagagtagac atccccctcc ttgccgctgg 3240
gagagccaag gcctatgcca cctgcagcgt ctgagcggcc gcctgtcctt ggtggccggg 3300
ggtgggggcc tgctgtgggt cagtgtgcca ccctctgcag ggcagcctgt gggagaaggg 3360
acagcgggta aaaagagaag gcaagctggc aggagggtgg cacttcgtgg atgacctcct 3420
tagaaaagac tgaccttgat gtcttgagag cgctggcctc ttcctccctc cctgcagggt 3480
agggggcctg agttgagggg cttccctctg ctccacagaa accctgtttt attgagttct 3540
gaaggttgga actgctgcca tgattttggc cactttgcag acctgggact ttagggctaa 3600
ccagttctct ttgtaaggac ttgtgcctct tgggagacgt ccacccgttt ccaagcctgg 3660
gccactggca tctctggagt gtgtgggggt ctgggaggca ggtcccgagc cccctgtcct 3720
tcccacggcc actgcagtca ccccgtctgc gccgctgtgc tgttgtctgc cgtgagagcc 3780
caatcactgc ctatacccct catcacacgt cacaatgtcc cgaattccca gcctcaccac 3840
cccttctcag taatgaccct ggttggttgc aggaggtacc tactccatac tgagggtgaa 3900
attaagggaa ggcaaagtcc aggcacaaga gtgggacccc agcctctcac tctcagttcc 3960
actcatccaa ctgggaccct caccacgaat ctcatgatct gattcggttc cctgtctcct 4020
cctcccgtca cagatgtgag ccagggcact gctcagctgt gaccctaggt gtttctgcct 4080
tgttgacatg gagagagccc tttcccctga gaaggcctgg ccccttcctg tgctgagccc 4140
acagcagcag gctgggtgtc ttggttgtca gtggtggcac caggatggaa gggcaaggca 4200
cccagggcag gcccacagtc ccgctgtccc ccacttgcac cctagcttgt agctgccaac 4260
ctcccagaca gcccagcccg ctgctcagct ccacatgcat agtatcagcc ctccacaccc 4320
gacaaagggg aacacacccc cttggaaatg gttcttttcc cccagtccca gctggaagcc 4380
atgctgtctg ttctgctgga gcagctgaac atatacatag atgttgccct gccctcccca 4440
tctgcaccct gttgagttgt agttggattt gtctgtttat gcttggattc accagagtga 4500
ctatgatagt gaaaagaaaa aaaaaaaaaa aaaaggacgc atgtatcttg aaatgcttgt 4560
aaagaggttt ctaacccacc ctcacgaggt gtctctcacc cccacactgg gactcgtgtg 4620
gcctgtgtgg tgccaccctg ctggggcctc ccaagttttg aaaggctttc ctcagcacct 4680
gggacccaac agagaccagc ttctagcagc taaggaggcc gttcagctgt gacgaaggcc 4740
tgaagcacag gattaggact gaagcgatga tgtccccttc cctacttccc cttggggctc 4800
cctgtgtcag ggcacagact aggtcttgtg gctggtctgg cttgcggcgc gaggatggtt 4860
ctctctggtc atagcccgaa gtctcatggc agtcccaaag gaggcttaca actcctgcat 4920
cacaagaaaa aggaagccac tgccagctgg ggggatctgc agctcccaga agctccgtga 4980
gcctcagcca cccctcagac tgggttcctc tccaagctcg ccctctggag gggcagcgca 5040
gcctcccacc aagggccctg cgaccacagc agggattggg atgaattgcc tgtcctggat 5100
ctgctctaga ggcccaagct gcctgcctga ggaaggatga cttgacaagt caggagacac 5160
tgttcccaaa gccttgacca gagcacctca gcccgctgac cttgcacaaa ctccatctgc 5220
tgccatgaga aaagggaagc cgcctttgca aaacattgct gcctaaagaa actcagcagc 5280
ctcaggccca attctgccac ttctggtttg ggtacagtta aaggcaaccc tgagggactt 5340
ggcagtagaa atccagggcc tcccctgggg ctggcagctt cgtgtgcagc tagagcttta 5400
cctgaaagga agtctctggg cccagaactc tccaccaaga gcctccctgc cgttcgctga 5460
gtcccagcaa ttctcctaag ttgaagggat ctgagaagga gaaggaaatg tggggtagat 5520
ttggtggtgg ttagagatat gcccccctca ttactgccaa cagtttcggc tgcatttctt 5580
cacgcacctc ggttcctctt cctgaagttc ttgtgccctg ctcttcagca ccatgggcct 5640
tcttatacgg aaggctctgg gatctccccc ttgtggggca ggctcttggg gccagcctaa 5700
gatcatggtt tagggtgatc agtgctggca gataaattga aaaggcacgc tggcttgtga 5760
tcttaaatga ggacaatccc cccagggctg ggcactcctc ccctcccctc acttctccca 5820
cctgcagagc cagtgtcctt gggtgggcta gataggatat actgtatgcc ggctccttca 5880
agctgctgac tcactttatc aatagttcca tttaaattga cttcagtggt gagactgtat 5940
cctgtttgct attgcttgtt gtgctatggg gggagggggg aggaatgtgt aagatagtta 6000
acatgggcaa agggagatct tggggtgcag cacttaaact gcctcgtaac ccttttcatg 6060
atttcaacca catttgctag agggagggag cagccacgga gttagaggcc cttggggttt 6120
ctcttttcca ctgacaggct ttcccaggca gctggctagt tcattccctc cccagccagg 6180
tgcaggcgta ggaatatgga catctggttg ctttggcctg ctgccctctt tcaggggtcc 6240
taagcccaca atcatgcctc cctaagacct tggcatcctt ccctctaagc cgttggcacc 6300
tctgtgccac ctctcacact ggctccagac acacagcctg tgcttttgga gctgagatca 6360
ctcgcttcac cctcctcatc tttgttctcc aagtaaagcc acgaggtcgg ggcgagggca 6420
gaggtgatca cctgcgtgtc ccatctacag acctgcagct tcataaaact tctgatttct 6480
cttcagcttt gaaaagggtt accctgggca ctggcctaga gcctcacctc ctaatagact 6540
tagccccatg agtttgccat gttgagcagg actatttctg gcacttgcaa gtcccatgat 6600
ttcttcggta attctgaggg tggggggagg gacatgaaat catcttagct tagctttctg 6660
tctgtgaatg tctatatagt gtattgtgtg ttttaacaaa tgatttacac tgactgttgc 6720
tgtaaaagtg aatttggaaa taaagttatt actctgatta aa 6762
<210> 38
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 38
ataccttcca ccaaattctt ta 22
<210> 39
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 39
taaagaattt ggtggaaggt at 22
<210> 40
<211> 150
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 40
ctggaggctt gctttgggct gtatgctgat accttccacc aaattcttta ttttggcctc 60
tgactgataa agaattgtgg aaggtatcag gacacaaggc cctttatcag cactcacatg 120
gaacaaatgg ccaccgtggg aggatgacaa 150
<210> 41
<211> 150
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 41
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctgataaagg gccttgtgtc 60
ctgatacctt ccacaattct ttatcagtca gaggccaaaa taaagaattt ggtggaaggt 120
atcagcatac agcccaaagc aagcctccag 150
<210> 42
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 42
ataagtcctt tactaaggag c 21
<210> 43
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 43
gctccttagt aaaggactta t 21
<210> 44
<211> 148
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 44
ctggaggctt gctttgggct gtatgctgat aagtccttta ctaaggagct tttggcctct 60
gactgagctc cttgtaagga cttatcagga cacaaggccc tttatcagca ctcacatgga 120
acaaatggcc accgtgggag gatgacaa 148
<210> 45
<211> 148
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 45
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctgataaagg gccttgtgtc 60
ctgataagtc cttacaagga gctcagtcag aggccaaaag ctccttagta aaggacttat 120
cagcatacag cccaaagcaa gcctccag 148
<210> 46
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 46
gattttgaag tcccgagcca a 21
<210> 47
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 47
ttggctcggg acttcaaaat c 21
<210> 48
<211> 148
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 48
ctggaggctt gctttgggct gtatgctgga ttttgaagtc ccgagccaat tttggcctct 60
gactgattgg ctcggattca aaatccagga cacaaggccc tttatcagca ctcacatgga 120
acaaatggcc accgtgggag gatgacaa 148
<210> 49
<211> 148
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 49
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctgataaagg gccttgtgtc 60
ctggattttg aatccgagcc aatcagtcag aggccaaaat tggctcggga cttcaaaatc 120
cagcatacag cccaaagcaa gcctccag 148
<210> 50
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 50
ggaaatgttg gatgtggcca tgt 23
<210> 51
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 51
acatggccac atccaacatt tcc 23
<210> 52
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 52
ctggaggctt gctttgggct gtatgctggg aaatgttgga tgtggccatg tttttggcct 60
ctgactgaac atggcacacc aacatttccc aggacacaag gccctttatc agcactcaca 120
tggaacaaat ggccaccgtg ggaggatgac aa 152
<210> 53
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 53
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctgataaagg gccttgtgtc 60
ctgggaaatg ttggtgtgcc atgttcagtc agaggccaaa aacatggcca catccaacat 120
ttcccagcat acagcccaaa gcaagcctcc ag 152
<210> 54
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 54
ggtgcagata attaataagt tcgcttatta attatctgca ccttc 45
<210> 55
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 55
gaaggtgcag ataattaata agcgaactta ttaattatct gcacc 45
<210> 56
<211> 139
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 56
tggaggcttg ctgaaggctg tatgctgttg tcggtgcaga taattaataa gttcgcttat 60
taattatctg caccttcagg acacaaggcc tgttactagc actcacatgg aacaaatggc 120
caccgtggga ggatgacaa 139
<210> 57
<211> 139
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 57
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctagtaacag gccttgtgtc 60
ctgaaggtgc agataattaa taagcgaact tattaattat ctgcaccgac aacagcatac 120
agccttcagc aagcctcca 139
<210> 58
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 58
ttgtagacta tttgcacact g 21
<210> 59
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 59
cagtgtgcaa atagtctaca a 21
<210> 60
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 60
ttgtcatcct cccacggtgg ccatttgttc catgtgagtg ctagtaacag gccttgtgtc 60
ctttgtagac tatttgcaca ctgcatctgt ggcttcactc agtgtgcaaa tagtctacaa 120
gacaacagca tacagccttc agcaagcctc ca 152
<210> 61
<211> 152
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 61
tggaggcttg ctgaaggctg tatgctgttg tcttgtagac tatttgcaca ctgagtgaag 60
ccacagatgc agtgtgcaaa tagtctacaa aggacacaag gcctgttact agcactcaca 120
tggaacaaat ggccaccgtg ggaggatgac aa 152
<210> 62
<211> 4321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 62
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
tccctaggtt ctagaaccgg tgacgtctcc catggtgaag cttggatctg aattcggtac 300
cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc 360
cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca 420
ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt 480
caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg 540
ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag 600
tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt 660
accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc cccctcccca 720
cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg 780
gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg 840
agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt tatggcgagg 900
cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg 960
ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 1020
gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctcagc gctgtaatta 1080
gcgcttggtt taatgacggc ttgttggagg cttgctgaag gctgtatgct gttgtcggtg 1140
cagataatta ataagttcgc ttattaatta tctgcacctt caggacacaa ggcctgttac 1200
tagcactcac atggaacaaa tggccaccgt gggaggatga caatttctgt ggctgcgtga 1260
aagccttgag gggctccggg agctagagcc tctgctaacc atgttcatgc cttcttcttt 1320
ttcctacagc tcctgggcaa cgtgctggtt attgtgctgt ctcatcattt tggcaaagaa 1380
ttcctcgaag atccgaaggg aaagtcttcc acgactgtgg gatccgttcg aagatatcac 1440
cggttgagcc accatgtgga ccctggtgag ctgggtggcc ctgaccgccg gcctggtggc 1500
cggcacccgc tgccccgacg gccagttctg ccccgtggcc tgctgcctgg accccggcgg 1560
cgccagctac agctgctgcc gccccctgct ggacaagtgg cccaccaccc tgagccgcca 1620
cctgggcggc ccctgccagg tggacgccca ctgcagcgcc ggccacagct gcatcttcac 1680
cgtgagcggc accagcagct gctgcccctt ccccgaggcc gtggcctgcg gcgacggcca 1740
ccactgctgc ccccgcggct tccactgcag cgccgacggc cgcagctgct tccagcgcag 1800
cggcaacaac agcgtgggcg ccatccagtg ccccgacagc cagttcgagt gccccgactt 1860
cagcacctgc tgcgtgatgg tggacggcag ctggggctgc tgccccatgc cccaggccag 1920
ctgctgcgag gaccgcgtgc actgctgccc ccacggcgcc ttctgcgacc tggtgcacac 1980
ccgctgcatc acccccaccg gcacccaccc cctggccaag aagctgcccg cccagcgcac 2040
caaccgcgcc gtggccctga gcagcagcgt gatgtgcccc gacgcccgca gccgctgccc 2100
cgacggcagc acctgctgcg agctgcccag cggcaagtac ggctgctgcc ccatgcccaa 2160
cgccacctgc tgcagcgacc acctgcactg ctgcccccag gacaccgtgt gcgacctgat 2220
ccagagcaag tgcctgagca aggagaacgc caccaccgac ctgctgacca agctgcccgc 2280
ccacaccgtg ggcgacgtga agtgcgacat ggaggtgagc tgccccgacg gctacacctg 2340
ctgccgcctg cagagcggcg cctggggctg ctgccccttc acccaggccg tgtgctgcga 2400
ggaccacatc cactgctgcc ccgccggctt cacctgcgac acccagaagg gcacctgcga 2460
gcagggcccc caccaggtgc cctggatgga gaaggccccc gcccacctga gcctgcccga 2520
cccccaggcc ctgaagcgcg acgtgccctg cgacaacgtg agcagctgcc ccagcagcga 2580
cacctgctgc cagctgacca gcggcgagtg gggctgctgc cccatccccg aggccgtgtg 2640
ctgcagcgac caccagcact gctgccccca gggctacacc tgcgtggccg agggccagtg 2700
ccagcgcggc agcgagatcg tggccggcct ggagaagatg cccgcccgcc gcgccagcct 2760
gagccacccc cgcgacatcg gctgcgacca gcacaccagc tgccccgtgg gccagacctg 2820
ctgccccagc ctgggcggca gctgggcctg ctgccagctg ccccacgccg tgtgctgcga 2880
ggaccgccag cactgctgcc ccgccggcta cacctgcaac gtgaaggccc gcagctgcga 2940
gaaggaggtg gtgagcgccc agcccgccac cttcctggcc cgcagccccc acgtgggcgt 3000
gaaggacgtg gagtgcggcg agggccactt ctgccacgac aaccagacct gctgccgcga 3060
caaccgccag ggctgggcct gctgccccta ccgccagggc gtgtgctgcg ccgaccgccg 3120
ccactgctgc cccgccggct tccgctgcgc cgcccgcggc accaagtgcc tgcgccgcga 3180
ggccccccgc tgggacgccc ccctgcgcga ccccgccctg cgccagctgc tgtgacaatt 3240
gttaattaag tttaaaccct cgaggccgca agcttatcga taatcaacct ctggattaca 3300
aaatttgtga aagattgact ggtattctta actatgttgc tccttttacg ctatgtggat 3360
acgctgcttt aatgcctttg tatcatgcta ttgcttcccg tatggctttc attttctcct 3420
ccttgtataa atcctggttg ctgtctcttt atgaggagtt gtggcccgtt gtcaggcaac 3480
gtggcgtggt gtgcactgtg tttgctgacg caacccccac tggttggggc attgccacca 3540
cctgtcagct cctttccggg actttcgctt tccccctccc tattgccacg gcggaactca 3600
tcgccgcctg ccttgcccgc tgctggacag gggctcggct gttgggcact gacaattccg 3660
tggtgttgtc ggggaaatca tcgtcctttc cttggctgct cgcctgtgtt gccacctgga 3720
ttctgcgcgg gacgtccttc tgctacgtcc cttcggccct caatccagcg gaccttcctt 3780
cccgcggcct gctgccggct ctgcggcctc ttccgcgtct tcgccttcgc cctcagacga 3840
gtcggatctc cctttgggcc gcctccccgc atcgataccg tcgactagag ctcgctgatc 3900
agcctcgact gtgccttcta gttgccagcc atctgttgtt tgcccctccc ccgtgccttc 3960
cttgaccctg gaaggtgcca ctcccactgt cctttcctaa taaaatgagg aaattgcatc 4020
gcattgtctg agtaggtgtc attctattct ggggggtggg gtggggcagg acagcaaggg 4080
ggaggattgg gaagacaata gcaggcatgc tggggagaga tccacgataa caaacagctt 4140
ttttggggtg aacatattga ctgaattccc tgcaggttgg ccactccctc tctgcgcgct 4200
cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt tggtcgcccg 4260
gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac taggggttcc 4320
t 4321
<210> 63
<211> 4552
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 63
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60
cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120
gccaactcca tcactagggg ttcctgctag ctctgggtat ttaagcccga gtgagcacgc 180
agggtctcca ttttgaagcg ggaggttacg cgttcgtcga ctactagtgg gtaccagagc 240
aaaaaaattg tcatcctccc acggtggcca tttgttccat gtgagtgcta gtaacaggcc 300
ttgtgtcctt tgtagactat ttgcacactg catctgtggc ttcactcagt gtgcaaatag 360
tctacaagac aacagcatac agccttcagc aagcctccag tggtctcata cagaacttat 420
aagattccca aatccaaaga catttcacgt ttatggtgat ttcccagaac acatagcgac 480
atgcaaatat tgcagggcgc cactcccctg tccctcacag ccatcttcct gccagggcgc 540
acgcgcgctg ggtgttcccg cctagtgaca ctgggcccgc gattccttgg agcgggttga 600
tgacgtcagc gtttcccatg gtgaagcttg gatctgatcc ctaggttcta gaaccggtga 660
cattcggtac cctagttatt aatagtaatc aattacgggg tcattagttc atagcccata 720
tatggagttc cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga 780
cccccgccca ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt 840
ccattgacgt caatgggtgg actatttacg gtaaactgcc cacttggcag tacatcaagt 900
gtatcatatg ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca 960
ttatgcccag tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt 1020
catcgctatt accatggtcg aggtgagccc cacgttctgc ttcactctcc ccatctcccc 1080
cccctcccca cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg 1140
ggcggggggg gggggggggc gcgcgccagg cggggcgggg cggggcgagg ggcggggcgg 1200
ggcgaggcgg agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa agtttccttt 1260
tatggcgagg cggcggcggc ggcggcccta taaaaagcga agcgcgcggc gggcgggagt 1320
cgctgcgacg ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc 1380
ggctctgact gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctccgg 1440
gctgtaatta gcgcttggtt taatgacggc ttgttttctg tggctgcgtg aaagccttga 1500
ggggctccgg gagctagagc ctctgctaac catgttcatg ccttcttctt tttcctacag 1560
ctcctgggca acgtgctggt tattgtgctg tctcatcatt ttggcaaaga attcctcgaa 1620
gatccgaagg gaaagtcttc cacgactgtg ggatccgttc gaagatatca ccggttgagc 1680
caccatgtgg accctggtga gctgggtggc cctgaccgcc ggcctggtgg ccggcacccg 1740
ctgccccgac ggccagttct gccccgtggc ctgctgcctg gaccccggcg gcgccagcta 1800
cagctgctgc cgccccctgc tggacaagtg gcccaccacc ctgagccgcc acctgggcgg 1860
cccctgccag gtggacgccc actgcagcgc cggccacagc tgcatcttca ccgtgagcgg 1920
caccagcagc tgctgcccct tccccgaggc cgtggcctgc ggcgacggcc accactgctg 1980
cccccgcggc ttccactgca gcgccgacgg ccgcagctgc ttccagcgca gcggcaacaa 2040
cagcgtgggc gccatccagt gccccgacag ccagttcgag tgccccgact tcagcacctg 2100
ctgcgtgatg gtggacggca gctggggctg ctgccccatg ccccaggcca gctgctgcga 2160
ggaccgcgtg cactgctgcc cccacggcgc cttctgcgac ctggtgcaca cccgctgcat 2220
cacccccacc ggcacccacc ccctggccaa gaagctgccc gcccagcgca ccaaccgcgc 2280
cgtggccctg agcagcagcg tgatgtgccc cgacgcccgc agccgctgcc ccgacggcag 2340
cacctgctgc gagctgccca gcggcaagta cggctgctgc cccatgccca acgccacctg 2400
ctgcagcgac cacctgcact gctgccccca ggacaccgtg tgcgacctga tccagagcaa 2460
gtgcctgagc aaggagaacg ccaccaccga cctgctgacc aagctgcccg cccacaccgt 2520
gggcgacgtg aagtgcgaca tggaggtgag ctgccccgac ggctacacct gctgccgcct 2580
gcagagcggc gcctggggct gctgcccctt cacccaggcc gtgtgctgcg aggaccacat 2640
ccactgctgc cccgccggct tcacctgcga cacccagaag ggcacctgcg agcagggccc 2700
ccaccaggtg ccctggatgg agaaggcccc cgcccacctg agcctgcccg acccccaggc 2760
cctgaagcgc gacgtgccct gcgacaacgt gagcagctgc cccagcagcg acacctgctg 2820
ccagctgacc agcggcgagt ggggctgctg ccccatcccc gaggccgtgt gctgcagcga 2880
ccaccagcac tgctgccccc agggctacac ctgcgtggcc gagggccagt gccagcgcgg 2940
cagcgagatc gtggccggcc tggagaagat gcccgcccgc cgcgccagcc tgagccaccc 3000
ccgcgacatc ggctgcgacc agcacaccag ctgccccgtg ggccagacct gctgccccag 3060
cctgggcggc agctgggcct gctgccagct gccccacgcc gtgtgctgcg aggaccgcca 3120
gcactgctgc cccgccggct acacctgcaa cgtgaaggcc cgcagctgcg agaaggaggt 3180
ggtgagcgcc cagcccgcca ccttcctggc ccgcagcccc cacgtgggcg tgaaggacgt 3240
ggagtgcggc gagggccact tctgccacga caaccagacc tgctgccgcg acaaccgcca 3300
gggctgggcc tgctgcccct accgccaggg cgtgtgctgc gccgaccgcc gccactgctg 3360
ccccgccggc ttccgctgcg ccgcccgcgg caccaagtgc ctgcgccgcg aggccccccg 3420
ctgggacgcc cccctgcgcg accccgccct gcgccagctg ctgtgacaat tgttaattaa 3480
gtttaaaccc tcgaggccgc aagcttatcg ataatcaacc tctggattac aaaatttgtg 3540
aaagattgac tggtattctt aactatgttg ctccttttac gctatgtgga tacgctgctt 3600
taatgccttt gtatcatgct attgcttccc gtatggcttt cattttctcc tccttgtata 3660
aatcctggtt gctgtctctt tatgaggagt tgtggcccgt tgtcaggcaa cgtggcgtgg 3720
tgtgcactgt gtttgctgac gcaaccccca ctggttgggg cattgccacc acctgtcagc 3780
tcctttccgg gactttcgct ttccccctcc ctattgccac ggcggaactc atcgccgcct 3840
gccttgcccg ctgctggaca ggggctcggc tgttgggcac tgacaattcc gtggtgttgt 3900
cggggaaatc atcgtccttt ccttggctgc tcgcctgtgt tgccacctgg attctgcgcg 3960
ggacgtcctt ctgctacgtc ccttcggccc tcaatccagc ggaccttcct tcccgcggcc 4020
tgctgccggc tctgcggcct cttccgcgtc ttcgccttcg ccctcagacg agtcggatct 4080
ccctttgggc cgcctccccg catcgatacc gtcgactaga gctcgctgat cagcctcgac 4140
tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt ccttgaccct 4200
ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat cgcattgtct 4260
gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg gggaggattg 4320
ggaagacaat agcaggcatg ctggggagag atccacgata acaaacagct tttttggggt 4380
gaacatattg actgaattcc ctgcaggttg gccactccct ctctgcgcgc tcgctcgctc 4440
actgaggccg cccgggcaaa gcccgggcgt cgggcgacct ttggtcgccc ggcctcagtg 4500
agcgagcgag cgcgcagaga gggagtggcc aactccatca ctaggggttc ct 4552
<210> 64
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 64
aagagggtgt tctctatgta ggc 23
<210> 65
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 65
gctcctccaa catttgtcac tt 22
<210> 66
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 66
acacagtacc taccgttata gca 23
<210> 67
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 67
tgttgtcaca gtaacttgca tca 23
<210> 68
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 68
ctgggctaca ctgagcacc 19
<210> 69
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic polynucleotide
<400> 69
aagtggtcgt tgagggcaat g 21
Claims (41)
- (i) 서열식별번호(SEQ ID NO) 46 내지 61 중 어느 하나에 기재된 서열을 포함하는 억제성 핵산을 코딩하는 트랜스진을 포함하는 발현 구축물; 및
(ii) 상기 발현 구축물에 플랭킹된 2개의 아데노-연관 바이러스 (AAV) 역전된 말단 반복부 (ITR)
를 포함하는 단리된 핵산. - 제1항에 있어서, 트랜스진이 프로모터에 작동가능하게 연결된 것인 단리된 핵산.
- 제2항에 있어서, 프로모터가 닭 베타 액틴 (CBA) 프로모터인 단리된 핵산.
- 제2항에 있어서, CMV 인핸서를 추가로 포함하는 단리된 핵산.
- 제1항에 있어서, 우드척 간염 바이러스 전사후 조절 요소(Woodchuck hepatitis virus Posttranscriptional Regulatory Element: WPRE)를 추가로 포함하는 단리된 핵산.
- 제1항에 있어서, 소 성장 호르몬 폴리A 신호 테일을 추가로 포함하는 단리된 핵산.
- 제1항에 있어서, 각각의 ITR 서열이 야생형 AAV2 ITR 서열인 단리된 핵산.
- 제1항에 있어서, 각각의 ITR 서열이 트랜스진에 인접한 "D" 영역 (서열식별번호 14)을 포함하는 것인 단리된 핵산.
- 제1항에 있어서, ITR 서열 중 적어도 하나가 트랜스진 기준으로 ITR 서열의 외부에 위치하는 "D" 영역 (서열식별번호 14)을 포함하는 것인 단리된 핵산.
- 제1항에 있어서, 트랜스진 기준으로 5'에 위치하는 ITR 서열이 트랜스진에 인접한 "D" 영역 (서열식별번호 14)을 포함하고, 트랜스진 기준으로 3'에 위치하는 ITR 서열이 트랜스진 기준으로 ITR 서열의 외부에 위치하는 "D" 영역 (서열식별번호 14)을 포함하는 것인 단리된 핵산.
- 제10항에 있어서, 5' ITR의 핵산 서열이 서열식별번호 71의 뉴클레오티드 1 - 145이고, 3' ITR의 핵산 서열이 서열식별번호 71의 핵산 뉴클레오티드 4018 - 4162인 단리된 핵산.
- 제11항에 있어서, 5' ITR과 트랜스진 사이에 TRY 영역을 추가로 포함하고, 여기서 TRY 영역은 서열식별번호 15에 기재된 서열을 갖는 것인 단리된 핵산.
- 서열식별번호 46 내지 61 중 어느 하나에 기재된 서열을 포함하는 억제성 핵산을 코딩하는 트랜스진을 포함하는 발현 구축물을 포함하는 핵산을 포함하며, 상기 트린스진에 2개의 아데노-연관 바이러스 (AAV) 역전된 말단 반복부 (ITR)가 플랭킹된 것인 재조합 아데노-연관 바이러스 (rAAV) 벡터.
- 제13항에 있어서, 트랜스진이 프로모터에 작동가능하게 연결된 것인 rAAV 벡터.
- 제14항에 있어서, 프로모터가 닭 베타 액틴 (CBA) 프로모터인 rAAV 벡터.
- 제14항에 있어서, CMV 인핸서를 추가로 포함하는 rAAV 벡터.
- 제13항에 있어서, 우드척 간염 바이러스 전사후 조절 요소 (WPRE)를 추가로 포함하는 rAAV 벡터.
- 제13항에 있어서, 소 성장 호르몬 폴리A 신호 테일을 추가로 포함하는 rAAV 벡터.
- 제13항에 있어서, 각각의 ITR 서열이 야생형 AAV2 ITR 서열인 rAAV 벡터.
- 제13항에 있어서, 각각의 ITR 서열이 트랜스진에 인접한 "D" 영역 (서열식별번호 14)을 포함하는 것인 rAAV 벡터.
- 제13항에 있어서, ITR 서열 중 적어도 하나가 트랜스진 기준으로 ITR 서열의 외부에 위치하는 "D" 영역 (서열식별번호 14)을 포함하는 것인 rAAV 벡터.
- 제13항에 있어서, 트랜스진 기준으로 5'에 위치하는 ITR 서열이 트랜스진에 인접한 "D" 영역 (서열식별번호 14)을 포함하고, 트랜스진 기준으로 3'에 위치하는 ITR 서열이 트랜스진 기준으로 ITR 서열의 외부에 위치하는 "D" 영역 (서열식별번호 14)을 포함하는 것인 rAAV 벡터.
- 제22항에 있어서, 5' ITR의 핵산 서열이 서열식별번호 71의 뉴클레오티드 1 - 145이고, 3' ITR의 핵산 서열이 서열식별번호 71의 핵산 뉴클레오티드 4018 - 4162인 rAAV 벡터.
- 제23항에 있어서, 5' ITR과 트랜스진 사이에 TRY 영역을 추가로 포함하고, 여기서 TRY 영역은 서열식별번호 15에 기재된 서열을 갖는 것인 rAAV 벡터.
- (i) AAV 캡시드 단백질; 및
(ii) 제13항의 rAAV 벡터
를 포함하는 재조합 아데노-연관 바이러스 (rAAV). - 제25항에 있어서, AAV 캡시드 단백질이 AAV9 캡시드 단백질인 rAAV.
- 5'에서 3' 순으로
(a) 5' AAV ITR;
(b) CMV 인핸서;
(c) CBA 프로모터;
(d) 서열식별번호 46 내지 61 중 어느 하나에 기재된 서열을 포함하는 억제성 핵산을 코딩하는 트랜스진;
(e) WPRE;
(f) 소 성장 호르몬 폴리A 신호 테일; 및
(g) 3' AAV ITR
을 포함하는 핵산을 포함하는 재조합 아데노-연관 바이러스 (rAAV) 벡터. - (i) AAV 캡시드 단백질; 및
(ii) 제27항의 rAAV 벡터
를 포함하는 재조합 아데노-연관 바이러스 (rAAV). - 제28항에 있어서, AAV 캡시드 단백질이 AAV9 캡시드 단백질인 rAAV.
- 제15항의 rAAV 벡터를 포함하는 플라스미드.
- 서열식별번호 46 내지 61 중 어느 하나에 기재된 서열을 포함하는 억제성 핵산을 코딩하는 핵산을 포함하는 배큘로바이러스 벡터.
- (i) 하나 이상의 아데노-연관 바이러스 rep 단백질 및/또는 하나 이상의 아데노-연관 바이러스 cap 단백질을 코딩하는 제1 벡터; 및
(ii) 서열식별번호 46 내지 61 중 어느 하나에 기재된 서열을 포함하는 억제성 핵산을 코딩하는 핵산을 포함하는 제2 벡터
를 포함하는 세포. - 제32항에 있어서, 제1 벡터가 플라스미드이고, 제2 벡터가 플라스미드인 세포.
- 제33항에 있어서, 포유동물 세포이며, 임의로 여기서 포유동물 세포가 HEK293 세포인 세포.
- 제32항에 있어서, 제1 벡터가 배큘로바이러스 벡터이고, 제2 벡터가 배큘로바이러스 벡터인 세포.
- 제35항에 있어서, 곤충 세포이며, 임의로 여기서 곤충 세포가 SF9 세포인 세포.
- 제25항, 제26항, 제28항 및 제29항 중 어느 한 항의 rAAV를 제조하는 방법이며,
(i) 하나 이상의 아데노-연관 바이러스 rep 단백질 및/또는 하나 이상의 아데노-연관 cap 단백질을 코딩하는 제1 벡터, 및 서열식별번호 46 내지 61 중 어느 하나에 기재된 서열을 포함하는 억제성 핵산을 코딩하는 트랜스진을 포함하는 재조합 AAV 벡터를 세포로 전달하는 단계;
(ii) rAAV의 패키징을 허용하는 조건하에서 세포를 배양하는 단계; 및
(iii) rAAV 수집을 위해, 배양된 숙주 세포 또는 배양 배지를 수거하는 단계
를 포함하는 방법. - 제1항 내지 제12항 중 어느 한 항의 단리된 핵산, 제13항 내지 제24항 및 제27항 중 어느 한 항의 rAAV 벡터, 또는 제25항, 제26항, 제28항 및 제29항 중 어느 한 항의 rAAV를 포함하는, 알츠하이머병 또는 전두측두엽 치매 (FTD)를 앓거나 또는 앓을 것으로 의심되는 대상체를 치료하는 방법에 사용하기 위한 제약 조성물이며, 여기서 상기 방법은 상기 단리된 핵산, 상기 rAAV 벡터, 또는 상기 rAAV를 대상체에게 투여하는 단계를 포함하는 것인 제약 조성물.
- 제38항에 있어서, 투여가 대상체의 중추 신경계 (CNS)에의 직접 주사를 포함하며, 임의로 여기서 직접 주사는 대뇌내 주사, 실질내 주사, 경막내 주사, 대수조내 주사, 또는 그의 임의의 조합인 제약 조성물.
- 제39항에 있어서, 대상체의 CNS에의 직접 주사가 컨벡션 강화 전달법 (CED)을 포함하는 것인 제약 조성물.
- 제38항에 있어서, 투여가 말초 주사를 포함하며, 임의로 여기서 말초 주사는 정맥내 주사인 제약 조성물.
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MX2020004005A (es) | 2020-10-05 |
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AU2023214366B2 (en) | 2023-10-12 |
BR112020006671A2 (pt) | 2020-12-01 |
EP3692151A1 (en) | 2020-08-12 |
JP2022060228A (ja) | 2022-04-14 |
AU2018346102A1 (en) | 2020-04-30 |
CA3078501A1 (en) | 2019-04-11 |
AU2023214366A1 (en) | 2023-08-31 |
JP2024014935A (ja) | 2024-02-01 |
JP2024037189A (ja) | 2024-03-18 |
AU2020260476A1 (en) | 2020-11-26 |
AU2018346102B2 (en) | 2023-05-11 |
JP2020537542A (ja) | 2020-12-24 |
IL273768A (en) | 2020-05-31 |
EP3692151A4 (en) | 2021-07-14 |
CN112501208A (zh) | 2021-03-16 |
US20200318115A1 (en) | 2020-10-08 |
WO2019070891A8 (en) | 2019-05-09 |
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