KR20220150323A - 코로나바이러스를 방지하는 백신 생산을 위한 완전 합성 장쇄 핵산 - Google Patents

코로나바이러스를 방지하는 백신 생산을 위한 완전 합성 장쇄 핵산 Download PDF

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KR20220150323A
KR20220150323A KR1020227033430A KR20227033430A KR20220150323A KR 20220150323 A KR20220150323 A KR 20220150323A KR 1020227033430 A KR1020227033430 A KR 1020227033430A KR 20227033430 A KR20227033430 A KR 20227033430A KR 20220150323 A KR20220150323 A KR 20220150323A
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마티아스 크리스텐
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Abstract

본 발명에는 백신으로서 COVID-19 및 기타 바이러스 질환을 방지하는, 고도로 정제된 형태의 SARS-CoV-2 및 관련 코로나바이러스의 외피 단백질, 바이러스 외피 및 바이러스 외피의 단편을 생산하는 생명공학적 제조 공정에 사용될 수 있는 완전 합성 장쇄 핵산이 기재되어 있다.

Description

코로나바이러스를 방지하는 백신 생산을 위한 완전 합성 장쇄 핵산
설명
본 발명은 독립항 1에 따른 완전 합성 장쇄 핵산에 관한 것이다. 본 발명은 추가로 이들 핵산 중 2개 이상을 포함하는 키트 및 핵산을 포함하는 적어도 하나의 플라스미드를 포함하는 생명공학적 생산 유닛에 관한 것이다. 본 발명은 추가로 상기 핵산을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것이다. 또한, 본 발명은 핵산을 사용하여 유전자 발현에 의해 수득 가능한 생성물을 포함하는 백신, 특히 코로나바이러스 SARS-CoV-2에 대한 백신뿐만 아니라 백신 생산 방법에 관한 것이다.
백신의 신속한 개발과 가용성은 많은 바이러스와 박테리아를 퇴치하는 데 중요하다. 적합한 백신의 생산은 다단계의 복잡한 과정이며 종종 높은 투자에도 불구하고 항상 성공적인 것은 아니다. 전형적으로, 적합한 백신을 개발하려면 수년이 걸린다. 역학적 관점에서 볼 때 새로운 질환의 출현에 대하여, 가능하다고 하여도, 너무 늦게 반응하는 것만이 가능하기 때문에, 이러한 긴 개발 시간은 특히 새로 출현하는 병원체 또는 돌연변이 병원체와 관련하여 주요 문제이다. 대조적으로, 새롭거나 심하게 돌연변이된 병원체의 분석, 확인 및 추가 검출은 이제 몇 주 또는 심지어 며칠 이내에 가능하며, 이는 지난 세기에 비해 크게 개선된 것이다.
이러한 맥락에서, 바이러스는 다른 종으로부터 인간으로의 확산을 야기하는 높은 돌연변이율을 갖고 있기 때문에 특별한 관심을 갖고 있다. 이러한 바이러스의 급속한 확산은 현대 의학에 주요한 도전과제가 된다. 오늘날(2020) 새로 출현하는 바이러스의 검출/확인과 백신 개발 사이의 일반적인 시간은 전형적으로 몇 년이다. 몇몇 경우에는, 충분한 사전 지식이 있으면 몇 개월 이내에 실험용 백신이 제공될 수 있다. 그러나, 이 기간은 수천 또는 수백만 명의 사람들이 감염될 때까지의 전형적인 시간보다 훨씬 더 길다. 그러한 급속한 확산은 현대 사회의 높은 이동성의 직접적인 결과이기도 하다.
이상적으로, 새로운 바이러스를 확인한 직후에, 충분한 양과 최고 품질의 백신을 이용할 수 있을 것이며, 어떻게든 새로운 바이러스의 초기 발병 지역에 접근한 모든 사람들에 대한 전국적인 백신접종을 허용할 것이다. 또한, 그러한 백신에 이상적인 방법은 바이러스의 진화 및 적응에 반응할 수 있을 것이다. 그러한 이상적인 생산 가능성은 오늘날 당업자에게 유토피아적인 것으로 보인다.
특히 최근, 코로나 팬데믹으로 백신 생산에 적합한 도구 개발의 관련성이 크게 증가했다. 코로나바이러스 SARS-CoV-2에 대한 백신 개발이 팬데믹 및 관련 글로벌 위기를 장기적으로 억제하는 유일한 입증된 수단이라는 데는 이견이 없다.
이러한 배경에서, 본 발명의 과제는 코로나바이러스 SARS-CoV-2에 대한 백신의 대량 및 고품질 생산을 가능하게 하는 기기를 제공하는 것이다.
상기 문제는 청구항 1에 따른 완전 합성 장쇄 핵산에 의해 해결된다. 본 발명의 바람직한 구현예는 구현예 및 종속항에 반영된다.
따라서, 본 발명은 특히 하기 구현예에 관한 것이다:
1. 적어도 4,000개의 염기를 갖는 완전 합성 장쇄 핵산으로서,
임의의 배열로 4개의 서열 부분 A-D 중 적어도 2개를 포함하거나,
서열 부분 A-D에 따른 데옥시리보핵산 서열에 상응하는 리보핵산 서열을 포함하는 것을 특징으로 하는 핵산:
여기서,
i) 서열 부분 A는
a) 서열 번호 50에 정의된 서열 또는 서열 번호 50에 정의된 서열과 적어도 98.5% 서열 동일성을 갖는 서열; 또는
b) 서열 번호 3에 정의된 서열 또는 서열 번호 3에 정의된 서열과 적어도 90% 서열 동일성을 갖는 서열
을 포함하고;
ii) 서열 부분 B는
a) 서열 번호 48에 정의된 서열 또는 서열 번호 48에 정의된 서열과 적어도 98.3% 서열 동일성을 갖는 서열; 또는
b) 서열 번호 7에 정의된 서열 또는 서열 번호 7에 정의된 서열과 적어도 90% 서열 동일성을 갖는 서열
을 포함하고;
iii) 서열 부분 C는
a) 서열 번호 49에 정의된 서열 또는 서열 번호 49에 정의된 서열과 적어도 97.2% 서열 동일성을 갖는 서열; 또는
b) 서열 번호 11에 정의된 서열 또는 서열 번호 11에 정의된 서열과 적어도 90% 서열 동일성을 갖는 서열
을 포함하고;
iv) 서열 부분 D는 서열 번호 17에 정의된 서열 또는 서열 번호 17에 정의된 서열과 적어도 98.5% 서열 동일성을 갖는 서열을 포함한다.
2. 구현예 1에 있어서, 정의된 서열에서 적어도 8,000개의 염기, 바람직하게는 적어도 20,000개의 염기를 갖는 것을 특징으로 하는 것인 핵산.
3. 구현예 1 또는 2에 있어서, 핵산이 하기를 추가로 포함하는 것인 핵산:
a) 1.) 서열 번호 51에 의해 정의된 ORF1ab 서열 또는 서열 번호 51과 적어도 98.5% 서열 동일성을 갖는 서열; 또는
2.) i) 서열 번호 59에 의해 정의된 ORF1b 서열 또는 서열 번호 59와 적어도 98.5% 서열 동일성을 갖는 서열; 및
ii) 서열 번호 58에 의해 정의된 ORF1 서열 또는 서열 번호 58과 적어도 98.6% 서열 동일성을 갖는 서열;
b) 서열 번호 52에 의해 정의된 ORF3a 서열 또는 서열 번호 52와 적어도 99% 서열 동일성을 갖는 서열; 및
c) 서열 번호 54에 의해 정의된 ORF7a 서열 또는 서열 번호 54와 적어도 99.5% 서열 동일성을 갖는 서열.
4. 구현예 3에 있어서, 핵산이 하기를 추가로 포함하는 것인 핵산:
a) 서열 번호 53에 의해 정의된 ORF6 서열 또는 서열 번호 53과 적어도 94.1% 서열 동일성을 갖는 서열; 및/또는
b) 서열 번호 55에 의해 정의된 ORF8 서열 또는 서열 번호 55와 적어도 99% 서열 동일성을 갖는 서열.
5. 구현예 1 내지 4 중 어느 하나에 있어서, 서열 부분 A 내지 C가 서열 번호 19에 따른 서열 또는 상응하는 리보핵산 서열에 상응하는 것을 특징으로 하는 것인 핵산.
6. 구현예 1 내지 5 중 어느 하나에 있어서, 핵산이 임의의 배열로 4개의 서열 부분 A-D 중 적어도 3개 또는 서열 부분 A-D에 따른 데옥시리보핵산 서열에 상응하는 리보핵산 서열을 갖는 4개 서열 부분 중 적어도 3개를 포함하는 것을 특징으로 하는 것인 핵산.
7. 구현예 1 내지 6 중 어느 하나에 있어서, 핵산이 임의의 배열로 4개의 서열 부분 A-D 또는 서열 부분 A-D에 따른 데옥시리보핵산 서열에 상응하는 리보핵산 서열을 갖는 4개의 서열 부분을 포함하는 것을 특징으로 하는 것인 핵산.
8. 구현예 1 내지 7 중 어느 하나에 있어서, 핵산이
서열 번호 15,
서열 번호 28,
서열 번호 29 및
서열 번호 30
으로 이루어진 적어도 하나의 서열을 추가로 포함하거나,
서열 부분인 서열 번호 15, 서열 번호 28, 서열 번호 29 및 서열 번호 30에 따른 데옥시리보핵산 서열 중 하나 또는 상응하는 리보핵산 서열을 포함하는 것을 특징으로 하는 것인 핵산.
9. 구현예 1 내지 8 중 어느 하나에 있어서, 1,000,000개 염기의 최대 크기, 바람직하게는 200,000개 염기의 최대 크기를 갖는 것을 특징으로 하는 것인 핵산.
10. 구현예 1 내지 9 중 어느 하나에 따른 핵산을 포함하는 벡터.
11. 구현예 10에 있어서, 벡터가 서열 번호 46 및 서열 번호 47에 의해 정의된 서열을 포함하는 것인 벡터.
12. 구현예 10 또는 11에 있어서, 벡터가 플라스미드 벡터인 것인 벡터.
13. 구현예 1 내지 9 중 어느 하나에 따른 2개 이상의 핵산을 포함하는 키트.
14. 구현예 13에 있어서, 핵산이 적어도 하나의 플라스미드, 바람직하게는 2개 이상의 플라스미드에 존재하는 것인 키트.
15. 구현예 10 내지 12 중 어느 하나에 따른 적어도 하나의 벡터를 포함하는 생명공학적 생산 유닛.
16. 구현예 1 내지 9 중 어느 하나에 따른 적어도 하나의 핵산, 구현예 10 내지 12 중 어느 하나에 따른 벡터, 구현예 13 또는 14에 따른 키트, 또는 구현예 15에 따른 생명공학적 생산 유닛을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질로서, 여기서, 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질은 구현예 1 내지 9 중 어느 하나에 따른 적어도 하나의 핵산을 패키징하는 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질.
17. 구현예 1 내지 9 중 어느 하나에 따른 적어도 하나의 핵산 및 생산 유기체에서 구현예 1 내지 9 중 어느 하나에 따른 적어도 하나의 핵산, 구현예 10 내지 12 중 어느 하나에 따른 벡터, 구현예 13 또는 14에 따른 키트를 사용하여 유전자 발현에 의해 수득 가능한 생성물을 포함하고, 특히 구현예 16에 따른 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신.
18. 구현예 17에 있어서, 단백질 성분 a, b1, b2, c1, c2, d1 또는 d2로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하고, 여기서,
(i) 단백질 성분은
a) SARS-CoV-2의 S 단백질과 유사한 서열 번호 14에 따른 서열 또는 서열 번호 14와 적어도 90% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 S 단백질과 유사한 서열 번호 18에 따른 서열 또는 서열 번호 18과 적어도 90% 서열 동일성을 갖는 서열
을 포함하고;
(ii) 단백질 성분 b1은
a) SARS-CoV-2의 외피 단백질 E와 유사한 서열 번호 6에 따른 서열 또는 서열 번호 6과 적어도 90% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 외피 단백질 E와 유사한 서열 번호 21에 따른 서열 또는 서열 번호 21과 적어도 90% 서열 동일성을 갖는 서열
을 포함하고;
단백질 성분 b2는 MHV59A의 외피 단백질 E 또는 등가 단백질과 유사한 서열 번호 8에 따른 서열 또는 서열 번호 8과 적어도 90% 서열 동일성을 갖는 서열을 포함하고;
(iii) 단백질 성분 c1은
a) SARS-CoV-2의 외피 단백질 M과 유사한 서열 번호 10에 따른 서열 또는 서열 번호 10과 적어도 90% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 막 단백질 M과 유사한 서열 번호 22에 따른 서열 또는 서열 번호 22와 적어도 90% 서열 동일성을 갖는 서열
을 포함하고;
단백질 성분 c2는 MHV59A의 막 단백질 M 또는 등가 단백질과 유사한 서열 번호 12에 따른 서열 또는 서열 번호 12와 적어도 90% 서열 동일성을 갖는 서열을 포함하고;
(iv) 단백질 성분 d1은
a) SARS-CoV-2의 뉴클레오캡시드 인단백질 N과 유사한 서열 번호 2에 따른 서열 또는 서열 번호 2와 적어도 90% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 뉴클레오캡시드 인단백질 N과 유사한 서열 번호 26에 따른 서열 또는 서열 번호 26과 적어도 90% 서열 동일성을 갖는 서열
을 포함하고;
단백질 성분 d2는 MHV59A의 뉴클레오캡시드 인단백질 N 또는 등가 단백질과 유사한 서열 번호 4에 따른 서열 또는 서열 번호 4와 적어도 90% 서열 동일성을 갖는 서열을 포함하는 것인 백신.
19. 하기의 연속 단계를 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신의 생산 방법:
a) 구현예 1 내지 9 중 어느 하나에 따른 뉴클레오티드 산 서열을 생명공학적 생산 유닛, 특히 세포주에 도입하는 단계로서,
단백질 성분 a, b1, b2, c1, c2, d1 또는 d2로 이루어진 군으로부터 선택된 단백질 성분 중 적어도 2개를 코딩하는 핵산 기반 mRNA는 번역에 의해 제조되는 것인 단계;
b) 단계 a)에서 생명공학적 생산 유닛으로부터 단백질 성분을 수득하는 단계; 및
c) 수득된 단백질 성분을 정제하여 코로나바이러스 SARS-CoV-2에 대한 백신을 수득하는 단계.
20. 하기의 연속 단계를 포함하는 구현예 16에 따른 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신의 생산 방법:
a) 구현예 1 내지 9 중 어느 하나에 따른 뉴클레오티드 산 서열을 생명공학적 생산 유닛에 도입하는 단계로서, 생명공학적 생산 유닛은 단백질 성분 a, b1, c1 및 d1로 이루어진 군으로부터 선택된 단백질 성분 중 적어도 하나를 코딩하는 뉴클레오티드 산을 포함하는 것인 단계;
b) 단계 a)에서 생명공학적 생산 유닛으로부터 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 수득하는 단계; 및
c) 수득된 단백질 성분을 정제하여 구현예 16에 따른 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신을 수득하는 단계.
21. 하기의 연속 단계를 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신의 생산 방법:
a) 구현예 10 내지 12 중 어느 하나에 따른 벡터를 증폭 생명공학적 생산 유닛에 도입하는 단계;
b) 증폭 생명공학적 생산 유닛에서 구현예 1 내지 9 중 어느 하나에 따른 뉴클레오티드 산을 증폭하는 단계;
c) 단계 b)에서 증폭된 뉴클레오티드 산을 수득하는 단계;
d) 구현예 19 또는 20에 따른 방법을 사용하여 코로나바이러스 SARS-CoV-2에 대한 백신을 수득하는 단계.
따라서, 본 발명은 적어도 4,000개의 염기를 갖는 완전 합성 장쇄 핵산에 관한 것으로, 핵산은 임의의 배열로 4개의 서열 부분 A-D 중 적어도 2개를 포함하거나, 여기서, i) 서열 부분 A는, a) 서열 번호 1에 정의된 서열 또는 서열 번호 1에 정의된 서열과 적어도 98.5% 서열 동일성을 갖는 서열; 또는 b) 서열 번호 3에 정의된 서열 또는 서열 번호 3에 정의된 서열과 적어도 90% 서열 동일성을 갖는 서열을 포함하고; ii) 서열 부분 B는, a) 서열 번호 5에 정의된 서열 또는 서열 번호 5에 정의된 서열과 적어도 98.3% 서열 동일성을 갖는 서열; 또는 b) 서열 번호 7에 정의된 서열 또는 서열 번호 7에 정의된 서열과 적어도 90% 서열 동일성을 갖는 서열을 포함하고; iii) 서열 부분 C는, a) 서열 번호 9에 정의된 서열 또는 서열 번호 9에 정의된 서열과 적어도 97.2% 서열 동일성을 갖는 서열; 또는 b) 서열 번호 11에 정의된 서열 또는 서열 번호 11에 정의된 서열과 적어도 90% 서열 동일성을 갖는 서열을 포함하고; iv) 서열 부분 D는, 서열 번호 13에 정의된 서열 또는 서열 번호 13에 정의된 서열과 적어도 98.5% 서열 동일성을 갖는 서열을 포함하거나; 서열 부분 A-D에 따른 데옥시리보핵산 서열에 상응하는 리보핵산 서열을 포함한다는 것을 특징으로 한다.
본 발명에 따른 핵산은 언급된 백신의 생산을 상당히 가속화할 수 있게 하고 바이러스 또는 변형, 특히 코로나바이러스 SARS-CoV-2에 매우 특이적인 잘 정의된 백신을 유도한다.
하기에 추가로 나타내는 바와 같이, 본 발명에 따른 핵산 서열에 포함된 서열 부분의 특정 서열 특징은 핵산이 완전히 합성적으로 생산되어 맞춤 제작될 수 있도록 한다. 따라서, 본 발명에 따른 핵산은 특정 구현예에서 RNA 대신 DNA일 뿐만 아니라, 자연 발생 서열과 대조적으로 화학적 합성에 의한 핵산의 완전한 합성 생산을 가능하게 하는 서열이 있다는 점에서 코로나바이러스에 자연적으로 존재하는 핵산과 상이하다.
궁극적으로, 본 발명에 따른 핵산은 따라서 분자 정밀도로 정의된 단백질 성분을 발현하는 것을 가능하게 한다. 이러한 단백질 성분이 백신으로서 투여되는 경우, 따라서 백신 접종자에게 최적의 예방접종(immunization)이 얻어질 수 있다. 동시에, 부정확하게 정의된 단백질 성분으로 매우 만연한 가능한 부작용의 위험이 크게 최소화된다. 또한, 단백질 발현에 사용되는 일반적인 발현 시스템을 사용하여 단백질 성분이 생산될 수 있다는 사실은 백신이 매우 신속하게 대량으로 이용 가능하게 될 수 있다는 것을 의미한다. 이것은 코로나바이러스 SARS-Cov-2와 같은 바이러스에 매우 중요한데, 상기 바이러스의 확산은 팬데믹의 비율을 가정했고 이에 따라 상기 바이러스의 억제는 광범위한 백신 투여를 필요로 한다.
다음 용어 및 개념은 본 발명의 맥락에서 사용될 것이다:
"핵산"이라는 용어는 DNA, RNA 및 이들의 임의의 변형을 지칭한다. 핵산은 단일 가닥 또는 이중 가닥일 수 있다. 변형은 핵산 리간드 염기 또는 핵산 리간드 전체에 대한 추가 전하, 분극성, 수소 결합, 정전기적 상호작용 및 유동성을 포함하는 다른 화학기를 제공하는 것들을 포함하지만, 이에 제한되지 않는다. 그러한 변형은 2'-위치당 변형, 5-위치 피리미딘 변형, 8-위치 퓨린 변형, 엑소사이클릭 아민에서의 변형, 4-티오우리딘의 치환, 5-브로모 또는 5-요오도-우라실의 치환; 골격 변형, 메틸화, 특이한 염기쌍 조합, 예컨대, 이소염기 이소시티딘 및 이소구아니딘을 포함하지만, 이에 제한되지 않는다. 변형은 또한 3' 및 5' 변형, 예컨대, 캡핑을 포함할 수 있다.
완전 합성. 화학적 관점에서, 핵산은 소위 염기로 불리는 반복 단위를 가진 매우 정교한 분자이다. 이러한 맥락에서 "완전 합성"이라는 용어는 본 발명에 따른 핵산이 화학 시약을 사용하는 일련의 화학 반응 단계에 의해 생성된다는 것을 의미한다. 효소와 같은 생화학적 보조제는 이미 더 긴 올리고머의 결합과 같은 개별 후속 생산 단계 동안에도 사용될 수 있다. 후자는 차례로 임의로 합성될 수 있다. 완전 합성 핵산은 화학적 생산 공정을 가능하게 하는 서열 특징을 가지며, 다음 서열 특징 중 하나 이상에서 자연 발생 핵산과 상이하다:
i) 하나 이상의 효소적 제한 부위, 특히, 당업자에게 공지된 IIS형 제한 엔도큐늘레아제에 대한 제한 부위의 부재;
ii) 상응하는 자연 발생 핵산과 비교하여, 완전 합성 핵산 내에 동일한 염기의 9개 초과의 연속적인 단위를 갖는 반복 핵산 서열의 부재 또는 감소된 발생;
iii) 상응하는 자연 발생 핵산과 비교하여, 12개 초과의 염기를 갖는 반복 염기쌍 서열의 부재 또는 감소된 발생;
iv) 상응하는 자연 발생 핵산에 비해, 그에 대한 역-상보성 서열로서 당업자에게 공지된 12개 초과의 염기 단위로 이루어진 간접적으로 반복되는 염기쌍 분절의 부재 또는 감소된 발생;
v) 상응하는 자연 발생 핵산에 비해, 당업자에게 공지된 중복 염기 단위(디뉴클레오티드 반복부)의 9회 초과의 연속적인 반복을 갖는 핵산 서열의 부재 또는 감소된 발생; 및
vi) 상응하는 자연 발생 핵산에 비해, 당업자에게 공지된 삼중 염기 단위(트리뉴클레오티드 반복부)의 5회 초과의 연속적인 반복을 갖는 핵산 서열의 부재 또는 감소된 발생.
일부 구현예에서, 완전 합성 핵산은 문헌(Venetz, J. E., et al., 2019, Proceedings of the National Academy of Sciences, 116(16), 8070-8079 및/또는 이의 SI 부록)에 기재된 방법에 따라 부분적으로 생성되고/되거나 서열 특징을 포함한다.
일부 구현예에서, 완전 합성 핵산은 화학적 생산 공정을 가능하게 하는 서열 특징을 포함하고, 전술한 서열 특징, 특히 전술한 서열 특징 i) - vi) 중 2개 이상에서 자연 발생 핵산과는 상이하다.
일부 구현예에서, 완전 합성 핵산은 화학적 생산 공정을 가능하게 하는 서열 특징을 포함하고, 전술한 서열 특징, 특히 전술한 서열 특징 i) - vi) 중 3개 이상에서 자연 발생 핵산과는 상이하다.
일부 구현예에서, 완전 합성 핵산은 화학적 생산 공정을 가능하게 하는 서열 특징을 포함하고, 전술한 서열 특징, 특히 전술한 서열 특징 i) - vi) 중 4개 이상에서 자연 발생 핵산과는 상이하다.
일부 구현예에서, 완전 합성 핵산은 화학적 생산 공정을 가능하게 하는 서열 특징을 포함하고, 전술한 서열 특징, 특히 전술한 서열 특징 i) - vi) 중 5개 이상에서 자연 발생 핵산과는 상이하다.
일부 구현예에서, 완전 합성 핵산은 화학적 생산 공정을 가능하게 하는 서열 특징을 포함하고, 전술한 서열 특징, 특히 전술한 서열 특징 i) - vi) 중 6개에서 자연 발생 핵산과는 상이하다. 장쇄 올리고뉴클레오티드는 짧은 단편으로 수년간 상업적으로 이용되어 왔으며, 전형적으로 60, 100 또는 200개 염기 조각을 생산한다. 엄청나게 더 긴 올리고뉴클레오티드는 오늘날 사용되는 합성이 합당한 양의 더 긴 핵산을 생산하기에는 오류율이 너무 높기 때문에 쉽게 이용할 수 없다. 따라서, 1,000개 미만의 염기를 가진 그러한 단편은 단쇄로 불리고, 1,000개 이상의 염기를 가진 핵산은 장쇄로 불린다. 1,000 내지 5,000개의 염기를 가진 장쇄 핵산은 오늘날 상당한 비용을 들여 생산될 수 있다(예를 들어, Twist Bioscience, Life-technologies라는 회사에 의함). 5,000개 초과의 염기를 가진 장쇄 핵산은 매우 복잡하지만 화학적으로 잘 정의된 분자이다. 각 분자는 위치, 유형 및 분자의 다른 부분과의 연결에 의해 고전적인 유기 화학의 관점에서 완전히 설명될 수 있다. 따라서, 2개의 동일한 장쇄 핵산은 이들의 크기 및 수만 내지 수백만 개의 원자를 포함하고 있다는 사실에도 불구하고, 모든 구성요소가 동일하고 동일하게 연결되어 있다는 점에서 동일하다.
말단기, 보호기의 임의의 잔기 또는 핵산의 합성으로부터의 기타 보조제에 대한 설명. 상기의 설명은 핵산의 염기 유형을 지칭한다. 당업자는 합성이 말단에서 절단되는 다양한 보조제에 의해 수행된다는 것을 알고 있다. 그러나, 때때로 그러한 기의 잔기가 남아 있거나 분자의 다른 부분이 합성 단계 전 또는 후에 유도체화된다. 그러한 기는 당업자에게 공지되어 있으며, 특히 폴리-A 테일, 변형된 DNA 염기, 고상(solid-phase) 합성으로부터의 절단 가능한 링커, 생화학적 기, 예컨대, 비오틴 또는 스트렙타비딘 등을 포함한다.
다른 가능한 변형 및 표준 방법에 사용되는 변형은 형광 마커에 관한 것이다. 이러한 변형 또는 이의 잔기는 상기의 설명에 영향을 미치지 않아야 하며, 위치 및 유형 염기당 이들의 위치에 있는 모든 n 개의 염기가 모든 염기에 대해 동일한 경우, 동일한 핵산의 군은 동일한 것으로 간주되어야 한다. 다시 말해서, 본 발명의 핵산은 또한, 본 발명에 의해 요구되는 염기 서열을 갖는 한, 상기 변형 또는 잔기를 갖는 핵산을 포함한다.
제1 양태에 따르면, 본 발명은 따라서 특정한 성질을 갖는 핵산에 관한 것이다. 이러한 특정한 성질은 염기 서열, 즉, 서열에 포함되며, 본 발명의 핵산이 특정한 성질을 갖는 경우에만 얻어진다. 이러한 성질은 특정한 분자의 직접적인 부분 또는 특정한 분자에 대한 화학적으로 포괄적인 전체 설명이다. 그러나, 단순함을 위해, 염기 서열은 본문의 해당 설명 내에 표시되어야 하며 항상 특정한 분자를 의미한다는 것을 분명히 해야 한다. 따라서, 염기 서열은 단지 실용적인 형태의 설명일 뿐이며, 분자 또는 그 IUPAC 명칭의 직접적인 표현보다 본 발명의 텍스트 표현에 명맥하게 더 적합하다.
본 발명의 분자는 화학에서 전형적으로 "R"로 약칭되고 이어서 "R"을 설명함으로써 더 자세히 설명될 수 있는, 하나 이상의 분자 부분을 가진 고전적인 화학적 제제의 군에 대한 설명과 유사한, 특정 서열의 존재를 통해 특정한 성질을 얻는다. 따라서, 본 발명에서, 유기 화학에서의 이러한 통상적인 절차와 유사하게, 본 발명의 장쇄 완전 합성 핵산의 특정한 성질을 담당하는 서열의 군이 기재되어 있다.
본 발명의 핵산은 이들이 외피 단백질 코로나바이러스의 4가지 유형의 단백질 중 적어도 2가지를 코딩하는 완전 합성 핵산을 포함한다는 사실을 특징으로 한다.
본원에 사용된 "코로나바이러스의 외피 단백질의 유형"이라는 용어는 코로나바이러스의 A 군, B 군, C 군 또는 D 군 단백질을 지칭한다. 본원에 사용된 용어 "A 군" 단백질은 코로나바이러스의 뉴클레오캡시드 단백질(N-유형)의 군을 지칭한다. 본원에 사용된 용어 "B 군"은 코로나바이러스의 외피 단백질(E-유형)의 군을 지칭한다. 본원에 사용된 용어 "C 군" 단백질은 코로나바이러스의 막 단백질(M-유형)을 지칭한다. 본원에 사용된 용어 "D 군" 단백질은 코로나바이러스의 글리코실화된 표면 단백질(S-유형)을 지칭한다.
일부 구현예에서, 본원에 기재된 핵산은 이들이 적어도 하나의 A 군 단백질 및 적어도 하나의 B 군 단백질을 코딩하는 핵산을 포함한다는 사실을 특징으로 한다. 일부 구현예에서, 본원에 기재된 핵산은 이들이 적어도 하나의 A 군 단백질 및 적어도 하나의 C 군 단백질을 코딩하는 핵산을 포함한다는 사실을 특징으로 한다. 일부 구현예에서, 본원에 기재된 핵산은 이들이 적어도 하나의 A 군 단백질 및 적어도 하나의 D 군 단백질을 코딩하는 핵산을 포함한다는 사실을 특징으로 한다. 일부 구현예에서, 본원에 기재된 핵산은 이들이 적어도 하나의 B 군 단백질 및 적어도 하나의 C 군 단백질을 코딩하는 핵산을 포함한다는 사실을 특징으로 한다. 일부 구현예에서, 본원에 기재된 핵산은 이들이 적어도 하나의 B 군 단백질 및 적어도 하나의 D 군 단백질을 코딩하는 핵산을 포함한다는 사실을 특징으로 한다. 일부 구현예에서, 본원에 기재된 핵산은 이들이 적어도 하나의 C 군 단백질 및 적어도 하나의 D 군 단백질을 코딩하는 핵산을 포함한다는 사실을 특징으로 한다.
일부 구현예에서, 본 발명의 핵산은 이들이 하기 사실을 특징으로 한다:
(a) 잘 정의된 서열에 4,000개 초과의 염기를 포함하고;
(b) 코로나바이러스의 4가지 유형의 외피 단백질을 코딩하는 4개의 서열 군 A-D에 할당된 특히 중요한 4개의 서열 중 적어도 2개를 포함하고, 여기서,
i) 제1 서열 A 군은 코로나바이러스의 뉴클레오캡시드 단백질 N의 외피 단백질을 코딩하고,
ii) 제2 서열 B 군은 코로나바이러스의 외피 단백질 E 유형의 외피 단백질을 코딩하고,
iii) 제3 서열 C 군은 코로나바이러스의 막 단백질 M 유형의 외피 단백질을 코딩하고,
iv) 제4 서열 D 군은 코로나바이러스의 글리코실화된 표면 단백질 S의 외피 단백질을 코딩한다.
본 설명에 개시된 서열 부분 A는 서열 번호 2 또는 서열 번호 4에 따른 상응하는 단백질 서열을 코딩하는 서열 번호 1 또는 서열 번호 3에 따른 서열을 포함한다. 일부 구현예에서, 서열 부분 A는 서열 번호 50에 의해 정의된 서열 또는 서열 번호 50과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 서열 부분 A는 서열 번호 3과 적어도 90% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 서열 부분 A는 서열 번호 2와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
일부 구현예에서, 서열 부분 A는 서열 번호 4와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
일부 구현예에서, 서열 부분 A는 서열 번호 2 및 서열 번호 4와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
본 설명에 개시된 서열 부분 B는 서열 번호 6 또는 서열 번호 8에 따른 상응하는 단백질 서열을 코딩하는 서열 번호 5 또는 서열 번호 7에 따른 서열을 포함한다. 일부 구현예에서, 서열 부분 B는 서열 번호 48에 의해 정의된 서열 또는 서열 번호 48과 적어도 98.3%, 적어도 98.6%, 적어도 99.1%, 또는 적어도 99.5% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 7과 적어도 90% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 6과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 8과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 6 및 서열 번호 8과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
본 설명에 개시된 서열 부분 C는 서열 번호 10 또는 서열 번호 12에 따른 상응하는 단백질 서열을 코딩하는 서열 번호 9 또는 서열 번호 11에 따른 서열을 포함한다. 일부 구현예에서, 서열 부분 C는 서열 번호 49에 의해 정의된 서열 또는 서열 번호 49와 적어도 97.2%, 적어도 97.4%, 적어도 97.6%, 적어도 97.8%, 적어도 98%, 적어도 98.2%, 적어도 98.4%, 적어도 98.6%, 적어도 98.8%, 적어도 99%, 적어도 99.2%, 적어도 99.4%, 적어도 99.6%, 적어도 99.8% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 서열 부분 C는 서열 번호 11과 적어도 90% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 12와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 10과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 10 및 서열 번호 12와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
본 설명에 개시된 서열 부분 D는 서열 번호 14에 따른 상응하는 단백질 서열을 코딩하는 서열 번호 13에 따른 서열을 포함한다. 일부 구현예에서, 서열 부분 D는 서열 번호 17에 의해 정의된 서열 또는 서열 번호 17과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 서열 부분 B는 서열 번호 14와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 아미노산 서열을 코딩하는 서열을 포함한다.
참조 서열에 대한 "퍼센트(%) 서열 동일성"이라는 용어는, 필요한 경우, 최대 퍼센트 서열 동일성을 달성하기 위해 서열을 정렬하고 갭을 도입한 후 참조 서열의 뉴클레오티드 또는 아미노산 잔기와 동일한 후보 서열의 뉴클레오티드 또는 아미노산 잔기의 백분율로서 정의되며, 서열 동일성의 일부로서 어떠한 보존적 치환도 고려하지 않는다. 퍼센트 아미노산 서열 동일성을 결정하기 위한 정렬은, 예를 들어, BLAST, BLAST-2, ALIGN 또는 Megalign(DNASTAR) 소프트웨어와 같은 공개적으로 이용 가능한 컴퓨터 소프트웨어를 사용하여 당업계의 기술 범위 내에 있는 다양한 방식으로 달성될 수 있다. 당업자는 비교되는 서열의 전장에 걸쳐 최대 정렬을 달성하는 데 필요한 임의의 알고리즘을 포함하여 서열을 정렬하기 위한 적절한 매개변수를 결정할 수 있다.
일부 구현예에서, 본 발명의 뉴클레오티드 산 서열은 단백질 생성물의 성질을 변경하지 않거나 실질적으로 변경하지 않음으로써 (예를 들어, 뉴클레오티드 산 서열 또는 이의 산물의 생산 과정을 촉진하기 위해) 변경된다.
일부 구현예에서, 본 발명의 뉴클레오티드 산 서열의 변경은 하기 군으로부터 선택된 적어도 하나의 변경을 포함한다:
1) 단백질 생성물의 성질을 변경하지 않거나 실질적으로 변경하지 않음으로써 참조 서열에 대한 염기 치환 삽입 또는 결실;
2) 코돈을 아주 밀접한 버전으로 대체; 및
3) 번역 속도를 미세 조정하는 (대체) ORF, 예측된 유전자 내부 전사 시작 부위 및/또는 서열 모티프(예측된 또는 암호) (예를 들어, 리보솜 중단 모티프)와 같은 단백질 코딩 서열 내에 존재하는 가상의 유전 요소의 수 감소.
본 발명의 변경된 뉴클레오티드 산 서열의 유전자가 기능을 유지하는지 여부를 시험하면, 아미노산 코드를 넘어서는 추가 정보가 적절한 기능을 위해 필요한 유전자를 확인할 것이다.
일부 구현예에서, 본원에 기재된 뉴클레오티드 산 서열은 코딩된 단백질 생성물의 생물학적 기능을 개선하도록 변경된다.
그러한 생물학적 기능은 안정성 향상, 생산 촉진(예를 들어, 추가 복제 개시 서열의 삽입), 복제 제한을 포함하지만 이에 제한되지 않는다.
일부 구현예에서, 본원에 기재된 뉴클레오티드 산 서열은 유사한 구조를 갖지만, 돌연변이된 바이러스의 단백질의 기능과 같은 대체 생물학적 기능을 갖는 관심 있는 적어도 하나의 대체 단백질을 코딩하도록 변경된다.
당업자는 관심 있는 적어도 하나의 대체 단백질을 코딩하는 서열(예를 들어, 돌연변이된 바이러스의 뉴클레오티드 산 서열)을 분석하고 관련 변경(예를 들어, 돌연변이)을 본원에 기재된 가장 유사한 뉴클레오티드 산 서열로 구현함으로써, 그러한 변경된 뉴클레오티드 서열을 얻을 수 있다. 일부 구현예에서, 본원에 기재된 가장 유사한 뉴클레오티드 산 서열은 서열 번호 1, 서열 번호 3, 서열 번호 5, 서열 번호 7, 서열 번호 9, 서열 번호 11, 서열 번호 13 및/또는 서열 번호 17에 의해 정의된 서열이다.
일부 구현예에서, 본원에 기재된 가장 유사한 뉴클레오티드 산 서열은 서열 번호 1, 서열 번호 5, 서열 번호 9, 서열 번호 13에 의해 정의된 서열이다.
일부 구현예에서, 본원에 기재된 코로나바이러스는 SARS-CoV-2이다. 일부 구현예에서, 본원에 기재된 SARS-CoV-2는 Lineage B.1.1.207, Lineage B.1.1.7, Cluster 5, 501.V2 변이체, Lineage P.1, Lineage B.1.429/CAL.20C, 및 Lineage B.1.525의 군으로부터 선택된 SARS-CoV-2 변이체이다.
일부 구현예에서, 본원에 기재된 SARS-CoV-2는 19A, 20A, 20C, 20G, 20H, 20B, 20D, 20F, 20I 및 20E의 군으로부터 선택된 Nextstrain 계통군에 의해 기재된 SARS-CoV-2 변이체이다.
일부 구현예에서, 관심 있는 적어도 하나의 대체 단백질을 코딩하는 서열은 적어도 하나의 SARS-CoV-2 변이체에 대해 특징적인 단백질을 코딩하는 서열을 포함한다. 일부 구현예에서, 적어도 하나의 SARS-CoV-2 변이체에 대해 특징적인 단백질은 서열 번호 18, 서열 번호 21, 서열 번호 22 및/또는 서열 번호 26과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열에 의해 코딩되는 단백질이다.
관련 변경의 이러한 구현은, 예를 들어, 적어도 하나의 염기의 삽입, 결실, 치환 및/또는 변형에 의해 달성될 수 있지만, 본원에 기재된 뉴클레오티드 산 서열의 백분율 이하일 수 있다.
일부 구현예에서, 본원에 기재된 가장 유사한 뉴클레오티드 산 서열은 서열 번호 1, 서열 번호 3, 서열 번호 5, 서열 번호 7, 서열 번호 9, 서열 번호 11, 서열 번호 13 및/또는 서열 번호 17에 의해 정의된 서열이다.
일부 구현예에서, 본원에 기재된 가장 유사한 뉴클레오티드 산 서열은 서열 번호 1, 서열 번호 5, 서열 번호 9 및/또는 서열 번호 13에 의해 정의된 적어도 하나의 서열이다.
일부 구현예에서, 삽입, 결실 또는 변형은 본원에 기재된 바와 같은 화학 시약을 사용하는 일련의 화학 반응 단계를 사용하여 본 발명의 핵산의 신규한 합성에 의해 달성될 수 있다.
변경된 서열은 서열 번호 1, 서열 번호 3, 서열 번호 5, 서열 번호 7, 서열 번호 9, 서열 번호 11, 서열 번호 13 및/또는 서열 번호 17에 의해 정의된 뉴클레오티드 산 서열보다 더 많거나 상이한 위치에서 변경된 서열의 화학적 생산 공정을 가능하게 하고/하거나 개선하는 서열 특징(예를 들어, 상기 기재된 서열 특징 i)-vi))을 포함할 수 있다.
IUPAC-분류 가능한 분자로의 이들의 가능한 변형은 당업자에게 공지되어 있다. 위에 정의된 바와 같은 데옥시리보핵산에 대한 대안으로서, 상응하는 리보핵산이 또한 존재할 수 있다. 다시 말해서, 서열 부분 A-D에 따른 데옥시리보핵산 서열에 추가하여, 본 발명에 따른 정의는 또한 상응하는 리보핵산 서열을 포함한다. 이들에서, 상응하는 리보핵산은 티민(T)이 우라실(U)로 대체된 위에 정의된 바와 같은 서열 부분을 갖는다.
MHV 및 SARS-CoV-2의 외피 단백질 E, M, N 및 S, 및 적용 가능하다면, MHV의 RNA-의존성 RNA 폴리머라제를 코딩하는 본 발명의 장쇄 핵산의 염기쌍 서열은 복잡한 발달의 결과를 나타내며, 제1 단계에서 유전자 코드의 중복성을 고려하여 상응하는 단백질의 천연 아미노산 서열부터 시작으로 계산함으로써 많은 수의 서열 변이체가 형성되었다.
특히, SARS-CoV-2의 단백질 E, M, N 및/또는 S를 코딩하는 본 발명의 장쇄 핵산의 염기쌍 서열은 복잡한 발달의 결과를 나타내며, 제1 단계에서 유전자 코드의 중복성을 고려하여 상응하는 단백질의 천연 아미노산 서열부터 시작으로 계산함으로써 많은 수의 서열 변이체가 형성되었다.
생성된 서열 트리로부터, 제2 단계에서, 각각의 코딩된 외피 단백질에 대한 염기쌍 서열은 첫째, 생물학적 기능의 측면에서 자연 서열과 가장 유사하고, 둘째, 화학적 생산 공정을 가능하게 하는 최적의 서열 특성을 또한 갖는 것으로 결정되었다.
또한, 서열은 야생형 바이러스의 구조적 단백질의 조합을 코딩한다. 이것은 T-세포 에피토프를 포함하여 면역계에 이용 가능한 광범위한 에피토프를 가능하게 한다(예를 들어, 문헌(Grifoni, A., et al., 2020, Cell, 181(7), 1489-1501) 참조). 이러한 광범위한 에피토프는 기존 면역이 있거나 없는 환자에서 광범위한 바이러스 변이체에 대한 면역을 가능하게 할 수 있다.
따라서, 본 발명은 본 발명의 핵산이 제한된 복제 능력을 갖지만, 원래의 바이러스와 유사한 항원 효과를 갖는 조합 바이러스-유사 단백질의 효율적인 생산을 가능하게 한다는 발견에 적어도 부분적으로 기반한다.
언급된 바와 같이, 본 발명에 따른 핵산은 적어도 4,000개의 염기 또는 염기쌍을 갖는다. 바람직하게는, 정의된 서열에서 적어도 8,000개의 염기, 특히 바람직하게는 적어도 20,000개의 염기를 갖는다. 또한, 핵산은 1,OOO,OOO개 염기의 최대 크기, 바람직하게는 200,000개 염기의 최대 크기를 갖는 것이 바람직하다.
큰 서열은 생산, 증폭 및/또는 발현하기 어려운 것으로 반복적으로 나타났지만, 다수의 염기는 원래 바이러스와 유사한 항원 효과를 갖는 바이러스-유사 단백질의 특정 조합을 일관되게 생산하는 데 유리하다.
본원에 제공된 수단 및 방법은 특정 길이 범위의 본 발명에 따른 핵산의 생산을 가능하게 한다(예를 들어, 실시예 1-3 참조).
따라서, 본 발명은 특정 길이 범위의 길이를 갖는 본 발명의 핵산이 제한된 복제 능력을 갖지만, 원래의 바이러스와 유사한 항원 효과를 갖는 조합 바이러스-유사 단백질의 효율적인 생산을 가능하게 한다는 발견에 적어도 부분적으로 기반한다.
본 발명에 따른 핵산은 단일 장쇄 핵산 또는 별도의 장쇄 핵산으로 분할된 형태로 존재할 수 있다.
일부 구현예에서, 본 발명에 따른 핵산은 단일 장쇄 핵산 또는 최대 4개의 별도의 장쇄 핵산으로 분할된 형태로 존재할 수 있다.
별도의 장쇄 핵산으로의 분리는 본 발명의 핵산의 증폭을 촉진할 수 있다(실시예 3).
추가의 바람직한 구현예에 따르면, 서열 부분 A-D는 서열 번호 16에 따라 배열된다.
또한, 서열 부분 D는 서열 번호 17로 이루어지고, 서열 번호 18에 따른 단백질 서열을 코딩하는 것이 바람직하다.
추가의 바람직한 구현예에 따르면, 서열 부분 A-C는 서열 번호 19에 따라 배열되고, 이에 의해 서열 부분 A는 서열 번호 26에 따른 단백질 서열을 코딩하고, 서열 부분 B는 서열 번호 21에 따른 단백질 서열을 코딩하고, 서열 부분 C는 서열 번호 22에 따른 단백질 서열을 코딩하고, 또한 서열 부분 A-C는 서열 번호 20, 서열 번호 22, 서열 번호 23, 서열 번호 24, 서열 번호 25 및 서열 번호 27을 코딩하는 서열로 확장될 수 있다.
일부 구현예에서, 본 발명은 본 발명에 따른 뉴클레오티드 산 서열에 관한 것이고, 여기서, 뉴클레오티드 산 서열은 서열 번호 19와 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열 또는 상응하는 리보핵산 서열에 의해 정의된다.
본 설명에 개시된 서열 부분 A-D를 코로나바이러스의 RNA-의존성 RNA 폴리머라제의 서열 번호 31 및 서열 번호 32에 따른 폴리단백질 서열을 코딩하는 서열 번호 15 또는 서열 번호 30에 따른 서열을 포함하는 서열 부분 E의 핵산 서열로 보충하는 것이 특히 바람직하다.
서열 번호 15 또는 서열 번호 30에 따른 서열은 본 발명에 따른 핵산의 성분을 나타낼 수 있고, 따라서 서열 부분 A-D의 2개 이상의 서열과 조합하여 동일한 분자에 존재할 수 있다. 독립 분자의 성분으로서 본 발명에 따른 핵산과 함께 키트에 존재하는 것도 생각할 수 있다. IUPAC-분류 가능한 분자로의 가능한 전달은 당업자에게 공지되어 있다.
서열 부분 E의 존재는 상응하는 단백질의 유전자 발현을 위해 RNA가 DNA 플라스미드 대신 생명공학적 생산 유닛에 도입되는 경우 관련이 있다. 이와 관련하여, 서열 부분 E가 서열 번호 33 또는 서열 번호 34에 따른 RNA 형태로 키트에 도입되어 키트에 존재하는 것도 생각할 수 있다. 이것은 아래의 특정 예의 맥락에서 더 설명될 것이다.
이러한 구체적인 서열은 첫째 자연 서열과의 이들의 유사성 또는 이들의 생물학적 기능과 관련하여, 그리고 둘째 화학적 생산 공정과 관련하여 특히 유리한 것으로 나타났다.
또 다른 바람직한 구현예에 따르면, 핵산은 임의의 배열로 4개의 서열 부분 A-D 중 적어도 3개를 포함한다. 이와 관련하여, 핵산이 임의의 배열로 4개의 서열 부분 A-D를 포함하는 것이 특히 바람직하다.
또한, 핵산은 하기의 군으로 이루어진 적어도 하나의 서열을 추가로 포함하는 것이 바람직하다:
서열 번호 15,
서열 번호 28,
서열 번호 29 및
서열 번호 30.
일부 구현예에서, 본 발명의 핵산은 서열 부분인 서열 번호 15, 서열 번호 28, 서열 번호 29 및 서열 번호 30에 따른 데옥시리보핵산 서열 중 하나 또는 상응하는 리보핵산 서열을 포함한다.
일부 구현예에서, 본 발명은 핵산이 서열 번호 28 또는 상응하는 리보핵산 서열을 포함하는 것을 특징으로 하는 본 발명에 따른 핵산에 관한 것이다.
일부 구현예에서, 본 발명은 핵산이 서열 번호 29 또는 상응하는 리보핵산 서열을 포함하는 것을 특징으로 하는 본 발명에 따른 핵산에 관한 것이다.
일부 구현예에서, 본 발명은 핵산이 서열 번호 28 및 서열 번호 29 또는 상응하는 리보핵산 서열을 포함하는 것으로 특징으로 하는 본 발명에 따른 핵산에 관한 것이다.
본 발명의 핵산은 표준 방법에 의해 세포주 또는 기타 생산 유기체에 혼입될 수 있고 바이러스의 단편 또는 전체 외피의 생산을 자극할 수 있는 특정한 성질을 갖는다. 이러한 목적을 위해 요구되는 표준 방법은 당업자에게 공지되어 있고 구체적인 예의 맥락에서 설명된다.
본 발명자들은 원래 바이러스의 효과적인 복제 가능성에 유용한 것으로 간주되었던 특정 ORF의 누락에도 불구하고, 바이러스 입자가 증폭되고 후속적으로 번역되고 성공적으로 어셈블리될 수 있다는 것을 발견하였다. 생성된 바이러스 입자는 여전히 세포를 감염시키고 비감염성 바이러스 단편의 생성을 유도할 수 있다.
본 발명자들은 SARS-CoV-2 바이러스 게놈(도 5 참조)의 ORF6 및 ORF8이 생략되거나 삭제될 수 있고, 바이러스 어셈블리가 가능한 상태로 유지됨을 발견하였다.
일부 구현예에서, 본 발명은 본 발명에 따른 핵산에 관한 것으로, 여기서, 핵산은 하기를 추가로 포함한다:
a) 1.) 서열 번호 51에 의해 정의된 ORF1ab 서열 또는 서열 번호 51과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
2.) i) 서열 번호 59에 의해 정의된 ORF1b 서열 또는 서열 번호 59와 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 및
ii) 서열 번호 58에 의해 정의된 ORF1a 서열 또는 서열 번호 58과 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열;
b) 서열 번호 52에 의해 정의된 ORF3a 서열 또는 서열 번호 52와 적어도 99%, 적어도 99.1%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열; 및
c) 서열 번호 54에 의해 정의된 ORF7a 서열 또는 서열 번호 54와 적어도 99.5% 서열 동일성을 갖는 서열.
일부 구현예에서, 본 발명은 본 발명에 따른 핵산에 관한 것으로, 여기서, 핵산은 하기를 추가로 포함한다:
a) 1.) 서열 번호 51에 의해 정의된 ORF1ab 서열 또는 서열 번호 51과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
2.) i) 서열 번호 59에 의해 정의된 ORF1b 서열 또는 서열 번호 59와 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 및
ii) 서열 번호 58에 의해 정의된 ORF1a 서열 또는 서열 번호 58과 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열;
b) 서열 번호 52에 의해 정의된 ORF3a 서열 또는 서열 번호 52와 적어도 99%, 적어도 99.1%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열;
c) 서열 번호 54에 의해 정의된 ORF7a 서열 또는 서열 번호 54와 적어도 99.5% 서열 동일성을 갖는 서열; 및
d) 서열 번호 55에 의해 정의된 ORF8 서열 또는 서열 번호 55와 적어도 99%, 적어도 99.3% 또는 적어도 99.6% 서열 동일성을 갖는 서열.
일부 구현예에서, 본 발명은 본 발명에 따른 핵산에 관한 것으로, 여기서, 핵산은 하기를 추가로 포함한다:
a) 1.) 서열 번호 51에 의해 정의된 ORF1ab 서열 또는 서열 번호 51과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
2.) i) 서열 번호 59에 의해 정의된 ORF1b 서열 또는 서열 번호 59와 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 및
ii) 서열 번호 58에 의해 정의된 ORF1a 서열 또는 서열 번호 58과 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8%, 또는 적어도 99.9% 서열 동일성을 갖는 서열;
b) 서열 번호 52에 의해 정의된 ORF3a 서열 또는 서열 번호 52와 적어도 99%, 적어도 99.1%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열;
c) 서열 번호 54에 의해 정의된 ORF7a 서열 또는 서열 번호 54와 적어도 99.5% 서열 동일성을 갖는 서열; 및
d) 서열 번호 53에 의해 정의된 ORF6 서열 또는 서열 번호 53과 적어도 94.1% 적어도 94.7%, 적어도 95.2%, 적어도 95.8%, 적어도 96.3%, 적어도 96.8%, 적어도 97.4%, 적어도 97.9%, 적어도 98.5%, 적어도 99%, 또는 적어도 99.6% 서열 동일성을 갖는 서열.
일부 구현예에서, 본 발명은 본 발명에 따른 핵산에 관한 것으로, 여기서, 핵산은 하기를 추가로 포함한다:
a) 1.) 서열 번호 51에 의해 정의된 ORF1ab 서열 또는 서열 번호 51과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
2.) i) 서열 번호 59에 의해 정의된 ORF1b 서열 또는 서열 번호 59와 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 및
ii) 서열 번호 58에 의해 정의된 ORF1a 서열 또는 서열 번호 58과 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열;
b) 서열 번호 52에 의해 정의된 ORF3a 서열 또는 서열 번호 52와 적어도 99%, 적어도 99.1%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열;
c) 서열 번호 54에 의해 정의된 ORF7a 서열 또는 서열 번호 54와 적어도 99.5% 서열 동일성을 갖는 서열;
d) 서열 번호 53에 의해 정의된 ORF6 서열 또는 서열 번호 53과 적어도 94.1% 적어도 94.7%, 적어도 95.2%, 적어도 95.8%, 적어도 96.3%, 적어도 96.8%, 적어도 97.4%, 적어도 97.9%, 적어도 98.5%, 적어도 99% 또는 적어도 99.6% 서열 동일성을 갖는 서열; 및
e) 서열 번호 55에 의해 정의된 ORF8 서열 또는 서열 번호 55와 적어도 99%, 적어도 99.3% 또는 적어도 99.6% 서열 동일성을 갖는 서열.
일부 구현예에서, 본 발명은 본 발명에 따른 핵산에 관한 것으로, 여기서, 핵산은 3'UTR, 5'UTR, TRS-L, TRS-B: S, TRS-B: orf3a, TRS-B: E, TRS-B: M, TRS-B: orf6, TRS-B: orf7a, TRS-B: orf8 및/또는 TRS-B: N을 추가로 포함한다.
일부 구현예에서, 본 발명은 본 발명에 따른 핵산에 관한 것으로, 여기서, 핵산은 서열 번호 57에 의해 정의된 3'UTR 및/또는 서열 번호 56에 의해 정의된 5'UTR을 추가로 포함한다.
일부 구현예에서, 본 발명은 본 발명에 따른 핵산에 관한 것으로, 여기서, 핵산은 서열 ACGAAC에 의해 정의된 TRS-L, TRS-B: S, TRS-B: orf3a, TRS-B: E, TRS-B: M, TRS-B: orf6, TRS-B: orf7a, TRS-B: 01T8 및/또는 TRS-B: N을 추가로 포함한다.
일부 구현예에서, 핵산 서열은 서열 번호 41에 의해 정의된 서열 또는 서열 번호 41과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 핵산 서열은 서열 번호 42에 의해 정의된 서열 또는 서열 번호 42와 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 핵산 서열은 서열 번호 43에 의해 정의된 서열 또는 서열 번호 43과 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 핵산 서열은 서열 번호 44에 정의된 서열 또는 서열 번호 44와 적어도 98.5%, 적어도 98.6%, 적어도 98.7%, 적어도 98.8%, 적어도 98.9%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 본원에 기재된 뉴클레오티드 산 서열은 상응하는 리보핵산 서열을 지칭한다.
SARS-CoV-2의 ORF6 및 ORF8은 I형 인터페론 신호전달 경로를 억제하므로(Li, J. Y., et al., 2020, Virus research, 286, 198074), 적절한 면역 반응을 방해한다. 따라서, 벡터에서 SARS-CoV-2의 ORF6 및/또는 ORF8 서열의 결실 또는 생략은 코딩된 바이러스 입자의 재현성을 제한할 뿐만 아니라, 이의 항원성을 증가시킨다.
따라서, 본 발명은 본 발명의 뉴클레오티드 산 서열이 놀라운 항원성 및 제한된 복제 능력을 갖는 바이러스 입자 또는 이의 일부를 코딩한다는 발견에 적어도 부분적으로 기반한다.
일부 구현예에서, 본 발명의 핵산 서열은 벡터 또는 벡터의 일부이다.
본원에 사용된 용어 "벡터"는 그 자체 및/또는 또 다른 핵산 분자를 세포 내로 전달 또는 수송할 수 있는 핵산 분자를 지칭한다. 전달된 핵산은 일반적으로 벡터 핵산 분자에 연결, 즉 이에 삽입된다. 벡터는 세포에서 자율 복제를 지시하는 서열을 포함할 수 있거나, 숙주 세포 DNA로의 통합을 허용하기에 충분한 서열을 포함할 수 있다. 일부 구현예에서, 본원에 기재된 벡터는 플라스미드(예를 들어, DNA 플라스미드 또는 RNA 플라스미드), 셔틀 벡터, 트랜스포존, 코스미드, 박테리아 인공 염색체 및 바이러스 벡터의 군으로부터 선택된 벡터이다.
특정 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 서열 부분 B를 포함하지 않고 서열 부분 A의 조절은 적어도 하나의 부속 단백질을 포함하지 않는다.
특정 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 플라스미드 벡터이다.
일부 구현예에서, 본원에 기재된 플라스미드 벡터는 복제의 기원을 결정하는 선택 마커와 서열을 갖는다. 일부 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 서열 번호 46 및 서열 번호 47에 정의된 서열을 포함한다.
일부 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 RNA-폴리머라제 프로모터를 코딩하는 적어도 하나의 서열, 및 음성 가닥 RNA의 합성을 가능하게 하고/하거나 양성 가닥 RNA 합성을 가능하게 하는 서열을 포함하는 적어도 하나의 비번역 영역을 포함한다.
일부 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 T7 프로모터를 코딩하는 적어도 하나의 서열, 및 음성 가닥 RNA의 합성을 가능하게 하고/하거나 양성 가닥 RNA 합성을 가능하게 하는 서열을 포함하는 적어도 2개의 비번역 영역을 포함한다.
일부 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 서열 번호 28에 의해 정의된 T7 프로모터를 코딩하는 적어도 하나의 서열, 및 서열 번호 56 및 57에 따른 서열을 포함하는 적어도 2개의 비번역 영역을 포함한다.
일부 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 플라스미드 벡터이다.
일부 구현예에서, 본 발명은 본 발명에 따른 벡터에 관한 것으로, 여기서, 벡터는 서열 번호 45에 정의된 서열을 포함한다.
일부 구현예에서, 본원에 기재된 뉴클레오티드 산 서열은 서열 번호 45와 적어도 50%, 적어도 60%, 적어도 70%, 적어도 80%, 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98% 또는 적어도 99% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 본원에 기재된 벡터는, i) 서열 번호 45와 적어도 50%, 적어도 60%, 적어도 70%, 적어도 80%, 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98% 또는 적어도 99% 서열 동일성을 갖고; ii) 서열 번호 47에 의해 정의된 선택 마커 및 서열 번호 46에 의해 정의된 복제 기원을 포함하는 서열을 포함한다.
일부 구현예에서, 본원에 기재된 벡터는 적어도 하나의 형질감염 증강제, 예를 들어, 올리고뉴클레오티드, 리포플렉스, 폴리머솜, 폴리플렉스, 덴드리머, 무기 나노입자 및 세포-투과 펩티드의 군으로부터 선택된 형질감염 증강제와 조합하여 사용된다.
본원에 기재된 벡터는 증폭 생명공학적 생산 유닛에서 본 발명의 핵산 서열의 효율적인 전달 및/또는 증폭을 위해 사용될 수 있다(실시예 3).
증폭 생명공학적 생산 유닛(예를 들어, 효모 세포)에서 증폭 생성물은 단리될 수 있으며 후속적으로 추가 생명공학적 생산 유닛(예를 들어, 인간 세포)에서 번역될 수 있다.
따라서, 본 발명은 본원에 기재된 벡터가 본원에 기재된 핵산의 효율적인 증폭 및 제한된 복제 능력을 갖지만, 높은 항원성을 갖는 조합 바이러스-유사 단백질의 효율적인 생산을 가능하게 한다는 발견에 적어도 부분적으로 기반한다. 본 발명의 핵산은 상기의 절차를 통해 단백질 및 기타 빌딩 블록을 포함하는 분산액을 생성한다.
원심분리 또는 크로마토그래피와 같은 당업자에게 공지된 적합한 분리 방법은 필요한 경우 사용된 생산 세포주 또는 기타 생산 보조제 또는 유기체의 잔류물로부터도 이러한 빌딩 블록을 분리하여 이들을 정제하는 데 사용될 수 있다.
일부 구현예에서, 본원에 기재된 빌딩 블록은 크로마토그래피, 침전, 초원심분리, 접선-유동 여과(tangential-flow filtration) 및 효소 분해의 군으로부터 선택된 적어도 하나의 분리 방법을 사용하여 정제된다.
이러한 임의로 정제된 바이러스 외피 또는 이의 단편은 백신의 기반을 나타내며, 이는 적용 유형에 따라 상이한 투여 형태로 전달된다.
전형적으로, 이 목적을 위해 애쥬번트, 저장 수명 개선을 위한 안정제, 염 및 완충제가 사용된다. 따라서, 백신은 본원에 기재된 장쇄의 완전 합성 핵산 생성물이다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산, 본 발명에 따른 벡터, 본 발명에 따른 키트 또는 본 발명에 따른 생명공학적 생산 유닛을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것으로, 여기서, 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질은 본 발명에 따른 적어도 하나의 핵산을 패키징한다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산, 본 발명에 따른 벡터, 본 발명에 따른 키트 또는 본 발명에 따른 생명공학적 생산 유닛을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피에 관한 것이다.
본원에 사용된 용어 "바이러스 외피"는 뉴클레오티드 산 서열(예컨대, 본 발명의 뉴클레오티드 산 서열)에 대한 안정화 기능을 갖는 단백질 층과 같은 단백질 어셈블리를 지칭한다. 일부 구현예에서, 본원에 기재된 바이러스 외피는 본 발명의 뉴클레오티드 산 서열을 인간 세포로 동화(assimilation)시키는 것을 가능하게 한다. 일부 구현예에서, 본원에 기재된 바이러스 외피는 스파이크 단백질, 외피 단백질 및 막 단백질을 포함한다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산, 본 발명에 따른 벡터, 본 발명에 따른 키트 또는 본 발명에 따른 생명공학적 생산 유닛을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피의 단편에 관한 것이다.
본원에 사용된 용어 "바이러스 외피의 단편"은 불완전한 바이러스 외피를 형성하는 적어도 2개의 어셈블리된 단백질을 지칭한다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산, 본 발명에 따른 벡터, 본 발명에 따른 키트 또는 본 발명에 따른 생명공학적 생산 유닛을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피 단백질에 관한 것이다.
본원에 사용된 용어 "바이러스 외피 단백질"은 바이러스 외피의 일부를 형성할 수 있는 적어도 하나의 단백질을 지칭한다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산, 본 발명에 따른 벡터, 본 발명에 따른 키트 또는 본 발명에 따른 생명공학적 생산 유닛을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것으로, 여기서, 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질은 본 발명에 따른 적어도 하나의 핵산을 패키징한다.
본원에 사용된 용어 "패키지"는 적어도 부분적으로 둘러싸고/둘러싸거나 연결된 것을 의미한다. 일부 구현예에서, 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 패키징된 본 발명의 핵산은 인간 세포로의 진입을 가능하게 한다.
본 발명의 핵산 및/또는 벡터의 생성물은, 생성물이 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질로 구현되는 경우, 상응하는 기능성 바이러스와 특히 높은 항원 유사성을 나타낸다. 따라서, 유발/유도된 면역 반응은 기능성 바이러스와의 실제 접촉에 특히 유익한 면역 반응을 유도할 가능성이 높을 것이다.
바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 패키징된 뉴클레오티드 산은 대상체의 인간 세포로 전달되어 인간 세포에서 바이러스 단백질의 생산을 유도할 수 있다. 그 결과 제한된 복제 능력을 가진 항원 바이러스-유사 단백질의 노출이 연장되고 강화된다.
따라서, 본 발명은 본원에 기재된 벡터가 제한된 복제 능력을 갖지만, 원래 바이러스와 유사한 항원 효과를 갖는 조합 바이러스-유사 단백질의 효율적인 생산을 가능하게 한다는 발견에 적어도 부분적으로 기반한다.
일부 구현예에서, 본 발명은 치료에 사용하기 위한 본 발명의 벡터에 관한 것이다.
일부 구현예에서, 본 발명은 치료에 사용하기 위한 생명공학적 생산 유닛에 관한 것이다.
일부 구현예에서, 본 발명은 치료에 사용하기 위한 본 발명의 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것이다.
본원에 사용된 용어 "치료" (및 "치료하다" 또는 "치료하는"과 같은 이의 문법적 변형)는 치료를 받는 개체의 자연적인 경과를 변경하려는 시도의 임상 개입을 지칭하며, 예방을 위해 또는 임상 병리학 과정 동안 수행될 수 있다. 치료의 바람직한 효과는 질환 발생 또는 재발 방지, 증상의 경감, 질환의 임의의 직접적인 또는 간접적인 병리학적 결과의 감소, 질환 진행 속도 감소, 질환 상태의 개선 또는 완화, 및 차도 또는 개선된 예후를 포함하지만, 이에 제한되지 않는다.
일부 구현예에서, 본 발명은 SARS-CoV-2 감염의 치료에 사용하기 위한 본 발명의 벡터, 생명공학적 생산 유닛, 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것이다.
일부 구현예에서, 본 발명은 SARS-CoV-2 감염의 예방에 사용하기 위한 본 발명의 벡터, 생명공학적 생산 유닛, 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것이다.
일부 구현예에서, 본 발명은 활성 SARS-CoV-2 감염의 치료에 사용하기 위한 본 발명의 벡터, 생명공학적 생산 유닛, 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것이다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산 및 생산 유기체에서 본 발명에 따른 적어도 하나의 핵산을 사용하여 유전자 발현에 의해 수득 가능한 생성물을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신에 관한 것이다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산 및 생산 유기체에서 본 발명에 따른 벡터를 사용하여 수득 가능한 생성물을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신에 관한 것이다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산 및 생산 유기체에서 본 발명에 따른 키트를 사용하여 수득 가능한 생성물을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신에 관한 것이다.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 핵산 및 생산 유기체에서 본 발명에 따른 적어도 하나의 핵산, 본 발명에 따른 벡터, 본 발명에 따른 키트를 사용하여 유전자 발현에 의해 수득 가능한 생성물을 포함하고, 특히 본 발명에 따른 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신에 관한 것이다.
본원에 사용된 용어 "백신"은 숙주에서 면역 반응을 유도/유발할 수 있고 감염 및/또는 질환을 치료 및/또는 예방할 수 있는 임의의 제제 또는 조성물을 지칭한다. 따라서, 그러한 제제의 비제한적인 예는 단백질, 폴리펩티드, 단백질/폴리펩티드 단편, 면역원, 항원, 펩티드 에피토프, 에피토프, 단백질, 펩티드 또는 에피토프의 혼합물뿐만 아니라, 핵산, 유전자 및/또는 유전자의 일부(관심 있는 폴리펩티드 또는 단백질 또는 이의 단편을 코딩함)를 포함한다.
본원에 사용된 용어 "코로나바이러스 SARS-CoV-2에 대한"은 SARS-CoV-2 감염의 치료 및/또는 예방을 지칭한다.
코로나바이러스의 구조 단백질은 면역 반응을 유발하는 것으로 나타났다(예를 들어, 문헌(Li, J. Y., et al., 2020, Virus research, 286, 198074; Walls, A. C., et al., 2020, Cell, 181(2), 281-292.e6; Chen, Z, et al., 2004, Clinical chemistry, 50(6), 988-995; Peng, Y., et al., 2020, Nature immunology, 21(11), 1336-1345.) 참조). 제공된 수단 및 방법은 동등한 에피토프 및/또는 면역 회피 기전이 감소된 입자를 갖는 백신의 생산 및 투여에 의해 동등한 면역 반응을 유도/유발하는 것을 가능하게 한다. 일부 구현예에서, 백신은 대상체에서 제한된 복제 능력을 갖는 입자의 생성을 유도한다.
따라서, 이러한 백신은 종종 동물 혈청으로부터 유래되어 분자적으로 일관성이 없는 고전적인 백신과는 크게 상이하다. 동물 유기체로부터의 생산은 전통적으로 선택 방법이다. 그러나, 분자적으로 명확하지 않은 생성물은 생산 배치에서 생산 배치에 이르기까지 대량 품질 문제와 편차를 초래한다. 이것은 또한 승인 기간이 길고 종종 뒤늦게만 발견되는 부작용과 관련이 있다. 따라서, 분자적으로 정의된 생성물 조성물은, 본 발명에 따른 핵산을 사용하여 수득할 수 있기 때문에 유리하다.
또한, 본원에 기재된 백신은 명확하게 정의되어 있고 광범위한 항원성 에피토프를 제공한다. 이는 백신이 면역 반응을 향상시키는 애쥬번트에 대한 요구사항이 낮거나 전혀 없다는 이점을 초래한다. 면역 반응을 향상시키는 그러한 보조제는 전형적으로 일부 환자에서 알레르기 반응과 같은 부작용과 관련이 있다. 또한, 본원에 기재된 바와 같은 백신의 주요 활성 성분은 단백질 기반이므로, 다른 백신(예를 들어, RNA 백신)에 비해 열안정성이 더 높다. 따라서, 본 발명의 백신은 이의 안정성으로 인해 쉽게 운반 가능하고 보관 가능하다.
따라서, 본 발명은 본원에 기재된 바와 같은 백신이 코로나바이러스 SARS-CoV-2에 대해 특히 유용하다는 발견에 적어도 부분적으로 기반한다.
일부 구현예에서, 본 발명은 본 발명에 따른 2개 이상의 핵산을 포함하는 키트에 관한 것이다.
일부 구현예에서, 본 발명은 서열 번호 35, 서열 번호 36, 서열 번호 37 및 서열 번호 38의 군으로부터 선택된 적어도 2개의 핵산을 포함하는 키트에 관한 것이다.
이러한 벡터의 조합에서, 키트는 인체 바이러스 단백질의 생산을 가능하게 한다.
핵산에 추가하여, 본 발명은 또한 2개 이상의 핵산을 포함하는 키트에 관한 것으로, 여기서, 핵산은 선행하는 청구항 중 어느 한 항에 따른 데옥시리보핵산(DNA) 및/또는 상응하는 염기쌍 서열을 갖는 상응하는 리보핵산(RNA)이다. 다시 말해서, 상응하는 리보핵산은 티민(T)이 우라실(U)로 대체된 위에 정의된 바와 같은 서열 부분을 갖는다.
본원에 기재된 키트는 필요한 생명공학적 생산 유닛(들) 및 시약을 수집하여 제조될 수 있다. 키트에 포함된 핵산이 DNA 형태로 존재하는 경우, 이들은 적어도 하나의 플라스미드, 바람직하게는 2개 이상의 플라스미드에 존재하는 것이 더 바람직하다. 이는 또한 아래의 구체적인 예의 맥락에서 기재된 바와 같이, 핵산이 상응하는 생명공학적 생산 유닛으로 쉽게 도입되도록 한다.
본 발명의 특정 구현예에서, 본 발명의 키트(상황에 따라 제조될 것임) 또는 본 발명의 방법 및 용도는 사용 설명서(들)를 추가로 포함하거나 제공될 수 있다. 예를 들어, 사용 설명서(들)는 당업자가 본원에 제공된 진단 용도에서 본 발명에 따른 본 발명의 키트를 (어떻게) 사용하는지를 안내할 수 있다. 특히, 상기 사용 설명서(들)는 본원에 제공된 방법 또는 용도를 사용하거나 이를 적용하기 위한 지침을 포함할 수 있다.
따라서, 본 발명은 바이러스 입자 및/또는 이의 부분의 효율적이고 안전한 생산을 가능하게 한다는 발견에 적어도 부분적으로 기반한다.
따라서, 또 다른 양태에 따르면, 본 발명은 또한 위에 정의된 바와 같은 적어도 하나의 플라스미드, 특히 2개 이상의 플라스미드를 포함하는 생명공학적 생산 유닛에 관한 것이다. 본 발명의 이러한 추가 양태가 기반이 되는 생산 유닛은 일반적으로 기재된 목적을 위해 당업자에게 공지된 생산 유기체 또는 세포주이다.
또 다른 양태에 따르면, 본 발명은 또한 적합한 생산 유기체 또는 세포주에서 상응하는 장쇄의 완전 합성 핵산의 적용으로부터 생성된 생성물에 관한 것이다. 이러한 생성물은 종종 추가 당 또는 지방산 기가 있는 외피 단백질 부류에 속한다. 구체적으로, 이러한 추가 양태는 따라서 위에 정의된 바와 같이 핵산을 사용하거나 키트를 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질에 관한 것이다.
본원에서 중요한 것은 할당이 수학적으로 명확하다는 것이다: 핵산 i는 그것에 정확히 의존하는 생성물 i를 생성한다. 심지어 약간 상이한 핵산 j는 또한 그것에 정확하게 의존하는 또 다른 생성물 j를 생성한다. 생성물과 핵산 간의 둘의 관계는 명확하고 설명 가능하다. 생성물 k의 각 유형은 핵산 k에 할당될 수 있다. 따라서, 핵산과 생성물, 즉 바이러스 외피 또는 이의 단편 간의 직접적인 관계를 말하는 것이 정당하다.
개별적인 분리 가능한 특징에 대한 대안이 본원에서 "구현예"로 제시되는 경우라면, 그러한 대안들이 자유롭게 조합되어 본원에 개시된 본 발명의 별개의 구현예를 형성할 수 있는 것으로 이해된다.
바이러스 외피의 어셈블리는 유기체와 유형에 따라 상이한 속도로 수행되고 청결도가 다양하므로, 실제로 외피와 이의 단편이 항상 함께 발견된다는 점을 언급해야 한다. 그러나, 필요한 경우, 이들은 일반적인 방법으로 분리될 수 있다.
일부 구현예에서, 본원에 기재된 외피는 크로마토그래피, 침전, 초원심분리, 접선-유동 여과 및 효소 분해의 군으로부터 선택된 적어도 하나의 정제 방법을 사용하여 정제된다.
본 발명의 추가 양태에 따르면, 본 발명의 장쇄 핵산의 직접 생성물은 따라서 임의의 정제 단계 및 가능한 보조 수단에 의해 백신으로 전환된다. 구체적으로, 이러한 추가 양태는 따라서 특히 하나 이상의 전술한 단백질 성분 또는 이의 부분을 포함하는 생산 유기체에서 위에 정의된 바와 같은 적어도 하나의 핵산 또는 키트를 사용하여 유전자 발현에 의해 수득 가능한 생성물을 포함하는 백신에 관한 것이다.
이 백신은 전형적으로 전술한 첨가제와 전형적으로 작은 농도의 상기 기재된 바이러스 외피 및/또는 단편을 갖는 생리 식염수이다.
본원에 기재된 백신이 다른 백신보다 애쥬번트의 효과에 덜 의존적이지만, 백신은 여전히 백신의 효과를 향상시키기 위해 애쥬번트를 포함할 수 있다. 일부 구현예에서, 백신은 무기 화합물(예를 들어, 칼륨 명반, 수산화알루미늄, 인산알루미늄, 수산화인산칼슘), 오일(예를 들어, 파라핀 오일, 땅콩 오일), 박테리아 생성물, 사포닌, 사이토카인(예를 들어, IL-1, IL-2, IL-12) 및 스쿠알렌의 군으로부터 선택된 적어도 하나의 애쥬번트를 포함한다.
일부 구현예에서, 백신은 경구 투여, 직장 투여, 흡입, 비강 투여, 비경구 투여, 근육내 투여, 피하 투여 및 피내 투여의 군으로부터 선택된 적어도 하나의 투여 경로에 의해 투여된다.
전형적인 백신은 투여 형태에 따라 주사되거나 점막을 통해 적용될 수 있다.
전술한 바와 같이, 백신은 특히 코로나바이러스 SARS-CoV-2에 대한 백신이다. 구체적으로, 이는 단백질 성분 a, b1, b2, c1 또는 c2, d1 또는 d2로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하고, 이에 의해,
(i) 단백질 성분 a는 SARS-CoV-2의 S 단백질과 유사한 서열 번호 14 및 서열 번호 18에 의해 정의된 서열을 포함하고;
(ii) 단백질 성분 b1은 SARS-CoV-2의 외피 단백질 E 또는 등가 단백질과 유사한 서열 번호 6 및 서열 번호 21에 제시된 서열을 포함하고, 단백질 성분 b2는 MHV59A의 외피 단백질 E와 유사한 서열 번호 8에 따른 서열을 포함하고;
(iii) 단백질 성분 c1은 SARS-CoV-2의 막 단백질 M과 유사한 서열 번호 10 및 서열 번호 22에 따른 서열을 포함하고, 단백질 성분 c2는 MHV59A의 막 단백질 M 또는 등가 단백질과 유사한 서열 번호 12에 따른 서열을 포함하고;
(iv) 단백질 성분 d1은 SARS-CoV-2의 뉴클레오캡시드 인단백질 N 또는 등가 단백질과 유사한 서열 번호 2 및 서열 번호 26에 따른 서열을 포함하고, 단백질 성분 d2는 MHV59A의 뉴클레오캡시드 인단백질 N과 유사한 서열 번호 4에 따른 서열을 포함한다.
단백질 성분 a, b1, b2, c1, c2, d1 또는 d2는 상응하는 자연 발생 유사체와 유사하지만 동일하지 않으며, 이는 상응하는 천연 핵산의 서열과 서열이 상이한 합성 핵산으로부터 생성된다는 사실로부터 비롯된다는 점에 주목해야 한다.
본 설명에 개시된 단백질 성분 a는 서열 번호 14 및 서열 번호 18에 따른 서열을 포함한다. 일부 구현예에서, 단백질 성분은 서열 번호 14와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 단백질 성분 a는 서열 번호 18과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
본 설명에 개시된 단백질 성분 b1은 서열 번호 6 및 서열 번호 21에 따른 서열을 포함한다. 일부 구현예에서, 단백질 성분 b1은 서열 번호 6과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 단백질 성분 b1은 서열 번호 21과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
본 설명에 개시된 단백질 성분 b2는 서열 번호 8에 따른 서열을 포함한다. 일부 구현예에서, 단백질 성분 b2는 서열 번호 8과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
본 설명에 개시된 단백질 성분 c1은 서열 번호 10 및 서열 번호 22에 따른 서열을 포함한다. 일부 구현예에서, 단백질 성분 c1은 서열 번호 10과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 단백질 성분 c1은 서열 번호 22와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
본 설명에 개시된 단백질 성분 c2는 서열 번호 12에 따른 서열을 포함한다. 일부 구현예에서, 단백질 성분 c2는 서열 번호 12와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
본 설명에 개시된 단백질 성분 d1은 서열 번호 2 및 서열 번호 26에 따른 서열을 포함한다. 일부 구현예에서, 단백질 성분 d1은 서열 번호 2와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 단백질 성분 d1은 서열 번호 26과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
본 설명에 개시된 단백질 성분 d2는 서열 번호 4에 따른 서열을 포함한다. 일부 구현예에서, 단백질 성분 d2는 서열 번호 4와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
본원에 기재된 아미노산 서열에 대해 특정 % 서열 동일성을 갖는 단백질 성분은, 예를 들어, 적어도 하나의 아미노산을, 그러나 서열 번호 2, 서열 번호 4, 서열 번호 6, 서열 번호 8, 서열 번호 10, 서열 번호 12, 서열 번호 14, 서열 번호 18, 서열 번호 21, 서열 번호 22, 및/또는 서열 번호 26의 아미노산 서열에 대해 아미노산의 10% 이하, 9% 이하, 8% 이하, 7% 이하, 6% 이하, 5% 이하, 4% 이하, 3% 이하, 2% 이하, 1% 이하, 0.9% 이하, 0.8% 이하, 0.7% 이하, 0.6% 이하, 0.5% 이하, 0.4% 이하, 0.3% 이하, 0.2% 이하 또는 0.1% 이하를 삽입, 결실, 치환 및/또는 변형하여 수득될 수 있다. 그러한 삽입, 결실, 치환 및/또는 변형은 원하는 삽입, 결실, 치환 및/또는 변형을 코딩하는 본원에 기재된 상응하는 뉴클레오티드 산 서열(예를 들어, 본원에 기재된 단백질 성분의 돌연변이된 변이체를 코딩하는 SARS-CoV-2 변이체의 뉴클레오티드 산 서열)을 기반으로 달성될 수 있다.
삽입, 결실, 치환 및/또는 변형은 또한 번역 후 변형의 결과일 수 있다. 일부 구현예에서, 본원에 기재된 단백질 성분은 생산 과정을 개선하기 위해 번역 후 변형된다. 일부 구현예에서, 본원에 기재된 단백질 성분은 기재된 단백질 성분의 적어도 하나의 단백질 성질, 예컨대, 항원성, 단백질 안정성, 약동학, 약력학, 약물과의 상호작용 및 애쥬번트와의 상호작용의 군으로부터 선택된 단백질 성질을 개선하기 위해 번역 후 변형된다. 일부 구현예에서, 본원에 기재된 단백질 성분은 적어도 다른 단백질 또는 펩티드에 연결된 작용기의 추가, 아미노산의 화학적 변형(예를 들어, 시트룰린화, 탈아미노화, 탈아미드화, 제거), 이황화 브릿지, 시스테인 아미노산 연결, 펩티드 결합 절단, 이소아스파르테이트 형성, 라세미화 및 단백질 스플라이싱의 군으로부터 선택된 기술에 의해 번역 후 변형된다.
따라서, 본원에 기재된 아미노산 서열은 본원에 기재된 뉴클레오티드 산 서열과 비례하는 % 서열 동일성이 반드시 중복되는 것은 아니다. 일부 구현예에서, 본 발명의 아미노산 서열은 변경된 뉴클레오티드 산 서열이 본원에 기재된 뉴클레오티드 산 서열과 상이한 것보다 서열 번호 2, 서열 번호 4, 서열 번호 6, 서열 번호 8, 서열 번호 10, 서열 번호 12, 서열 번호 14, 서열 번호 18, 서열 번호 21, 서열 번호 22 및/또는 서열 번호 26에 기재된 서열과 적어도 10%, 적어도 9%, 적어도 8%, 적어도 7%, 적어도 6%, 적어도 5%, 적어도 4%, 적어도 3%, 적어도 2%, 적어도 1%, 적어도 0.9%, 적어도 0.8%, 적어도 0.7%, 적어도 0.6%, 적어도 0.5%, 적어도 0.4%, 적어도 0.3%, 적어도 0.2%, 적어도 0.1% 이상 상이하다.
일부 구현예에서, 본 발명은 단백질 성분 a, b1, b2, c1 또는 c2, d1 또는 d2로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것으로, 여기서
(i) 단백질 성분 a는
a) SARS-CoV-2의 S 단백질과 유사한 서열 번호 14에 따른 서열 또는 서열 번호 14와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 S 단백질과 유사한 서열 번호 18에 따른 서열 또는 서열 번호 18과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열
을 포함하고;
(ii) 단백질 성분 b1은
a) SARS-CoV-2의 외피 단백질 E와 유사한 서열 번호 6에 따른 서열 또는 서열 번호 6과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 외피 단백질 E와 유사한 서열 번호 21에 따른 서열 또는 서열 번호 21과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열
을 포함하며;
단백질 성분 b2는 MHV59A의 외피 단백질 E 또는 등가 단백질과 유사한 서열 번호 8에 따른 서열 또는 서열 번호 8과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함하고;
(iii) 단백질 성분 c1은
a) SARS-CoV-2의 외피 단백질 E와 유사한 서열 번호 10에 따른 서열 또는 서열 번호 10과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 막 단백질 M과 유사한 서열 번호 22에 따른 서열 또는 서열 번호 22와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열
을 포함하고;
단백질 성분 c2는 MHV59A의 막 단백질 M 또는 등가 단백질과 유사한 서열 번호 12에 따른 서열 또는 서열 번호 12와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함하고;
(iv) 단백질 성분 d1은
a) SARS-CoV-2의 뉴클레오캡시드 인단백질 N과 유사한 서열 번호 2에 따른 서열 또는 서열 번호 2와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열; 또는
b) SARS-CoV-2의 뉴클레오캡시드 인단백질 N과 유사한 서열 번호 26에 따른 서열 또는 서열 번호 26과 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열
을 포함하고;
단백질 성분 d2는 MHV59A의 뉴클레오캡시드 인단백질 N 또는 등가 단백질과 유사한 서열 번호 4에 따른 서열 또는 서열 번호 4와 적어도 90%, 적어도 91%, 적어도 92%, 적어도 93%, 적어도 94%, 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99%, 적어도 99.1%, 적어도 99.2%, 적어도 99.3%, 적어도 99.4%, 적어도 99.5%, 적어도 99.6%, 적어도 99.7%, 적어도 99.8% 또는 적어도 99.9% 서열 동일성을 갖는 서열을 포함한다.
일부 구현예에서, 본 발명은 단백질 성분 a, b1, c1 및 d1로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 단백질 성분 b1, c1 및 d1로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 단백질 성분 a, c1 및 d1로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 단백질 성분 a, b1 및 d1로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 단백질 성분 a, b1 및 c1로 이루어진 군으로부터 선택된 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분 a 및 c1을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분 a 및 d1을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분 c1 및 d1을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분 a, 및 b1, c1 및 d1을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 단백질 성분 a, b1, c1 및 d1로 이루어진 군으로부터 선택된 적어도 3개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것이다.
일부 구현예에서, 본 발명은 단백질 성분 a, b1, c1 및 d1로 이루어진 군으로부터 선택된 3개의 분자적으로 정확하게 정의된 단백질 성분을 포함하는 본 발명에 따른 백신에 관한 것이다.
본원에 기재된 단백질 성분을 포함하는 본 발명에 따른 백신은 실질적이고 광범위한 면역 반응을 유발할 수 있다. 동시에, 백신은 대상체의 체내에서 복제되지 않는다는 점에서 복제 능력이 제한될 수 있다. 그러한 제한된 복제 능력, 예를 들어, 효율적인 복제를 위해 필요한 서열을 생략하거나 변경함으로써 달성될 수 있다.
따라서, 본 발명은 본원에 기재된 단백질 성분의 조합을 포함하는 백신이 항원 가능성을 크게 유지하면서 복제 능력에서 원하는 제한을 나타낼 수 있다는 발견에 적어도 부분적으로 기반한다.
또한, 본 발명은 핵산 기반 mRNA로부터 출발하여 형질감염에 의해 제1항 내지 제10항 중 어느 한 항에 따른 적어도 하나의 핵산을 생명공학적 생산 유닛, 특히 세포주에 도입하고, 단백질 성분 a, b1, b2, c1, c2, d1 또는 d2로 이루어진 군으로부터 선택된 단백질 성분 중 적어도 2개를 번역에 의해 제조하고, 이로부터 수득된 단백질 성분을 정제하는 연속 단계를 포함하는 백신 생산 방법에 관한 것이다.
일부 구현예에서, 본 발명은 하기의 연속 단계를 포함하는 본 발명에 따른 백신의 생산 방법에 관한 것이다:
a) 구현예 10 내지 14 중 어느 하나에 따른 벡터를 생명공학적 생산 유닛, 특히 세포주에 도입하는 단계로서,
여기서, 단백질 성분 a, b1, b2, c1, c2, d1 또는 d2로 이루어진 군으로부터 선택된 단백질 성분 중 적어도 2개를 코딩하는 핵산 기반 mRNA는 번역에 의해 제조되는 것인 단계;
b) 단계 a)에서 생명공학적 생산 유닛으로부터 단백질 성분을 수득하는 단계; 및
c) 수득된 단백질 성분을 정제하여 본 발명에 따른 백신을 수득하는 단계.
일부 구현예에서, 본 발명은 본 발명에 따른 적어도 하나의 벡터를 포함하는 생명공학적 생산 유닛에 관한 것이다.
용어 "생명공학적 생산 유닛" 및 "생산 유기체"는 본원에서 상호교환적으로 사용되며, 발현을 위해 본 발명의 핵산이 도입된 적어도 하나의 숙주 세포를 지칭하며, 그러한 세포의 자손, 유기체 및 그러한 세포 및/또는 그러한 세포의 자손을 포함하는 생명공학적 유닛을 포함한다. 숙주 세포는 계대 수에 관계없이 1차 형질전환된 세포 및 이로부터 유래된 자손을 포함하는 "형질전환체" 및 "형질전환된 세포"를 포함한다. 자손은 핵산 함량이 모세포와 완전히 동일하지 않을 수 있지만, 돌연변이를 포함할 수 있다. 원래 형질전환된 세포에서 스크리닝되거나 선택된 것과 동일한 기능 또는 생물학적 활성을 갖는 돌연변이 자손이 본원에 포함된다.
용어 "증폭 생명공학적 생산 유닛"은 큰 벡터(예를 들어, 4,000개 초과의 염기, 10,000개 초과의 염기, 35,000개 초과의 염기)의 증폭을 허용하는 임의의 생명공학적 생산 유닛을 지칭한다. 일부 구현예에서, 본원에 기재된 증폭 생명공학적 생산 유닛은 효모 세포를 포함한다.
특정 구현예에서, 숙주 세포는 줄기 세포이다. 다른 구현예에서, 숙주 세포는 분화된 세포이다.
본원에 기재된 생명공학적 생산 유닛은 SARS-CoV-2의 바이러스 진입을 허용하는 세포를 포함하여 생명공학적 생산 유닛의 세포 생성물이 생명공학적 생산 유닛의 추가 세포에 진입할 수 있는 경우 특히 유용하다. 생명공학적 생산의 세포에 대한 이러한 후속 감염은 벡터를 숙주 세포로 가져오는 과정을 촉진하고 가속화한다.
일부 구현예에서, 본원에 기재된 생명공학적 생산 유닛은 SARS-CoV-2의 바이러스 진입을 허용하는 세포를 포함한다. 일부 구현예에서, 본원에 기재된 생명공학적 생산 유닛은 인간 ACE2 수용체 또는 기능적 인간-유사 ACE2 수용체를 발현하는 세포를 포함한다. SARS-CoV-2의 바이러스 진입을 허용하는 인간-유사 ACE2 수용체는 당업자에게 공지되어 있다(예를 들어, 문헌(Damas, J., et al., 2020, Proceedings of the National Academy of Sciences, 117(36), 22311-22322) 참조).
일부에서, 본원에 기재된 생명공학적 생산 유닛은 HEK293, MDCK, 차이니즈 햄스터 난소(CHO), SF9, Vero, MRC 5, Per.C6, PMK 및 WI-38의 군으로부터 선택된 적어도 하나의 세포 유형을 포함한다.
일부 구현예에서, 본원에 기재된 생명공학적 생산 유닛은 적어도 부분적으로 인간인 세포 또는 적어도 부분적으로 인간 세포주의 세포를 포함한다.
일부 구현예에서, 본원에 기재된 생명공학적 생산 유닛은 그 안에 선택적으로 복제 가능한 본 발명의 뉴클레오티드 또는 본 발명의 벡터를 포함하는 바이러스 입자의 생산을 허용하는 세포를 포함하며, 그 세포는 생명공학적 생산 유닛의 세포에서는 완전히 복제될 수 있지만, 인체의 세포에서는 그렇지 않거나 실질적으로 복제되지 않는다. 이러한 선택적 복제 가능성은 바이러스 입자의 복제를 위한 상보적 단백질을 포함하는 세포에 의해 달성된다(예를 들어, 실시예 참조).
일부 구현예에서, 본원에 기재된 생명공학적 생산 유닛은 바이러스 복제를 위해 적어도 하나의 단백질을 발현할 수 있는 세포를 포함한다. 일부 구현예에서, 본원에 기재된 생명공학적 생산 유닛은 본 발명의 뉴클레오티드 산 서열 또는 본 발명의 벡터에 코딩되지 않은 바이러스 복제를 위한 적어도 하나의 단백질 성분을 발현할 수 있는 세포를 포함한다.
본 발명의 벡터에 의한 숙주 세포의 형질도입은 안정하거나 일시적인 형질도입에 의해 달성될 수 있다(예를 들어, 문헌(Stepanenko, A. A., and Heng, H. H., 2017, Mutation Research/Reviews in Mutation Research, 773, 91-103) 참조).
DNA가 제1 구현예에 따라 생산 유닛에 도입된다면, 이것은 일반적으로 이러한 목적에 적합한 플라스미드를 사용하여 수행된다.
대안적으로, DNA는 임의의 종류의 벡터에 의해 생명공학적 생산 유닛에 도입될 수 있다.
한편, RNA가 제2 구현예에 따라 도입된다면, 단백질 성분 a, b1, b2, c1, c2, d1 또는 d2를 코딩하는 서열에 추가하여 RNA-의존성 RNA 폴리머라제를 코딩하는 서열(서열 번호 30에 따름)이 도입된다. 이 서열은 템플릿으로서 존재하는 양성 RNA 가닥으로부터 음성 RNA 가닥을 먼저 형성한 다음, 이로부터 상응하는 메신저 RNA를 생성하는 것을 가능하게 한다.
절차의 이러한 제2 구현예의 맥락에서, 수득된 백신이 효소적 전사에 의해 수득 가능한 완전 합성 장쇄 리보핵산(서열 번호 33 또는 34에 따름)을 추가로 포함하는 것이 바람직하다.
절차의 이러한 제2 구현예의 맥락에서, 수득된 백신이 서열 번호 28에 따른 서열의 T7 전사를 통해 수득 가능한 완전 합성 장쇄 리보핵산(서열 번호 33 또는 34에 따름)을 추가로 포함하는 것이 또한 바람직하다.
"a," "an," 및 "the"는 본원에서 관사의 문법적 대상 중 하나 또는 하나 초과(즉, 적어도 하나, 또는 하나 이상)를 지칭하는 데 사용된다.
"또는"은 대안 중 하나, 둘 다 또는 이들의 임의의 조합을 의미하는 것으로 이해되어야 한다.
"및/또는"은 대안 중 하나 또는 둘 다를 의미하는 것으로 이해되어야 한다.
본 명세서 전반에 걸쳐, 문맥에 달리 요구하지 않는 한, "포함하다(comprise)", "포함하다(comprises)" 및 "포함하는(comprising)"이라는 단어는 언급된 단계 또는 요소 또는 단계 또는 요소의 군을 포함하지만 임의의 다른 단계 또는 요소 또는 단계 또는 요소의 군을 배제하지 않음을 의미하는 것으로 이해될 것이다.
"포함하다(include)" 및 "포함하다(comprise)"라는 용어는 동의어로 사용된다. "바람직하게는"은 다른 옵션을 배제하지 않는 일련의 옵션 중 하나의 옵션을 의미한다. "예를 들어"는 언급된 예로 제한되지 않는 하나의 예를 의미한다. "이루어진"이란 "이루어진"이라는 문구 뒤에 오는 모든 것을 포함하며 이에 제한되지 않는다.
본 명세서 전반에 걸쳐 "일 구현예(one embodiment)", "일 구현예(an embodiment)", "특정 구현예(particular embodiment)", "관련 구현예", "특정 구현예(certain embodiment)", "추가 구현예", "일부 구현예", "특정 실시예" 또는 "추가 구현예" 또는 이들의 조합에 대한 참조는 구현예와 관련하여 설명된 특정 특징, 구조 또는 특성이 본 발명의 적어도 일 구현예에 포함된다는 것을 의미한다. 따라서, 본 명세서 전반에 걸쳐 다양한 곳에서 전술한 문구의 출현은 반드시 모두 동일한 구현예를 지칭하는 것은 아니다. 또한, 특정 특징, 구조, 또는 특성은 하나 이상의 구현예에서 임의의 적합한 방식으로 조합될 수 있다. 또한, 일 구현예에서 특징의 긍정적인 언급은 특정 구현예에서 특징을 배제하기 위한 기초 역할을 하는 것으로 이해된다. 본 발명은 첨부된 도면과 함께 하기 설계 예에 의해 추가로 예시되며, 이는 청구범위에 기재된 본 발명의 범위를 제한하지 않는다.
도 1: SARS-CoV2의 뉴클레오캡시드 단백질(N) (서열 번호 35), 외피 단백질(E) (서열 번호 36), 막 단백질(M) (서열 번호 37) 및 스파이크 당단백질(S) (서열 번호 38)을 코딩하는 모노-시스트론 발현 플라스미드의 플라스미드 맵. 플라스미드 맵 내부의 숫자는 염기쌍에서의 DNA 좌표를 나타낸다. N, E, M 및 S의 단백질-코딩 서열은 화살표로 표시되며 서열 목록에 명시된 바와 같이 서열 번호 1, 2, 3 및 4 (N), 5, 6, 7 및 8 (E), 9, 10, 11 및 12 (M), 13 및 14 (S)의 DNA 및 단백질 서열을 나타낸다.
도 2: 모노-시스트론 발현 플라스미드 pcDNA34 syn N(서열 번호 35) (아래 도면)과 함께 실시예 2에 나타낸 바와 같이 세포주에서 백신 생산에 사용될 수 있는 폴리-시스트론 발현 작제물 COVAX191△N(서열 번호 33 및 39) (위 도면)의 게놈 맵. 숫자는 COVAX191△N에 대한 킬로베이스(K)의 DNA 좌표를 지칭하고 pcDNA34 syn N 작제물(서열 번호 35)에 대한 염기쌍 위치를 지칭한다. 폴리단백질 1a 및 1b, E, M S(위 도면) 및 뉴클레오캡시드 단백질 syn N(아래 도면)의 단백질-코딩 서열은 화살표로 표시된다.
도 3: 뉴클레오캡시드 단백질(N), 외피 단백질(E), 막 단백질(M) 및 스파이크 당단백질(S)에 대한 모노-시스트론, 플라스미드 기반 발현 작제물의 아가로스 겔 전기영동 크기 분리. 겔의 좌측은 뉴클레오캡시드 단백질(N), 외피 단백질(E) 및 막 단백질(M)에 대한 MHV A59(MHV) 유래 작제물을 나타낸다. 겔의 우측은 뉴클레오캡시드 단백질(N), 외피 단백질(E), 막 단백질(M) 및 스파이크 당단백질(S)에 대한 SARS-CoV2를 기반으로 하는 유래된 작제물을 나타낸다.
도 4: 원형 40,556 bp DNA 작제물 COVAX191△N(서열 번호 40) (위 도면) 및 38,383 bp DNA 작제물 COVAX191△N△HE(서열 번호 40) (아래 도면)의 상응하는 DNA 시퀀싱 커버 그래프가 있는 개략도. 화살표는 복제 폴리단백질 1A 및 1B(1A, 1B), 헤마글루티닌 에스테라제(HE), 스파이크 당단백질(S), 외피 단백질(E) 및 막 단백질(M)의 재코딩된 CDS에 대한 단백질-코딩 서열의 위치를 나타낸다. 단일 리튬 아세테이트 효모 형질전환을 사용하여 6개의 합성 DNA 블록으로부터 COVAX191△N 및 COVAX191△N△HE의 완전한 게놈을 어셈블리하고 영양요구성(auxotrophic) URA3 마커에 대해 선택하였다.
도 5: SARS-CoV-2 게놈 및 생성된 결실 변이체의 개략도.
표 S1: 에스. 세레비시아(S. cerevisiae) (효모)에서 COVAX191의 DNA 어셈블리 효율
실시예
하기 실시예는 세포가 코로나 바이러스 외피 또는 이의 단편을 생성하도록 자극하기 위해 외피 단백질 E, M, N 및 S를 코딩하는 본 발명의 장쇄 핵산이 어떻게 생산되고 사용되는지를 설명한다.
생산을 위해, 본 발명에 따른 (디지털) 서열은 화학적 DNA 합성 과정에 의해 물리적으로 존재하는 상응하는 장쇄 완전 합성 핵산 분자로 전달된다.
실시예 1
제1 실시예에서, 외피 단백질 E, M, N 및 S를 코딩하는 생성된 장쇄 완전 합성 핵산은 모노-시스트론성인데, 즉, 이들은 별도의 프로모터(SV40, CMV, EF-1, 치킨 β 액틴 프로모터 또는 하이브리드 프로모터) 및 기타 임의의 번역 개시 신호(Kozak 공통 서열) 및 핵 mRNA 배출 신호(Chuck Wood 서열)의 제어 하에 진핵 세포용 발현 플라스미드로 생산된다. 서열 번호 35, 서열 번호 36, 서열 번호 37 및 서열 번호 38 및 도 1에 나타낸 서열은 그러한 발현 시스템의 예로서 작용할 것이다. 다른 발현 플라스미드, 상응하는 내성 유전자 및 프로모터를 갖는 다른 구현예가 가능하고 당업자에게 공지되어 있다.
생성된 4개의 발현 플라스미드는 에스케리키아 콜리(Escherichia coli)에서 증폭되고 표준 화학-물리적 절차에 의해 정제된 다음, 형질감염에 의해 진핵 세포주(HEK293, 차이니즈 햄스터 난소(CHO), SF9, Vero)에 도입된다. 형질감염은 인산칼슘, 리포펙션, 전기천공과 같은 표준 절차에 의해 수행된다.
형질감염 후, 형질감염된 플라스미드 DNA로부터 시작하는 세포는 외피 단백질 E, M, N 및 S가 번역에 의해 발현되는 메신저 RNA(mRNA)를 번역하기 시작한다. 이러한 단백질은 세포에서 자발적으로 어셈블리되어 코로나 바이러스 외피를 형성한 다음, 세포에 의해 엑소시토시스(exocytosis)에 의해 배양 배지로 방출되고 이때 이들은 5-7일 후에 축적된다.
외피 단백질, 바이러스 외피 및 이들의 단편의 정제에는 화학적-물리적 공정이 사용된다. 이를 위해, 원심분리에 의해 세포 배양 상층액을 세포로부터 분리한다. 후속 단계에서, 바이러스 외피는 크로마토그래피 컬럼 분리 방법에 의해 배양 배지의 불순물 및 기타 성분으로부터 추가로 정제된다. 이와 같이 얻어진 코로나바이러스 외피로 이루어진 순수한 형태의 물질은 백신의 기반을 이루며, 그 후 적용 유형에 따라 투여를 위해 다양한 형태로 전환된다. 전형적으로, 이 목적을 위해 애쥬번트, 저장 수명 개선을 위한 안정제, 염 및 완충제가 사용된다. 따라서, 백신은 본원에 기재된 장쇄의 완전 합성 핵산 생성물이다.
실시예 2
제2 실시예에서, 외피 단백질 E, M 및 S를 코딩하는 장쇄의 완전 합성 핵산은 RNA-의존성 RNA 폴리머라제를 코딩하는 완전 합성 핵산과 함께 발현된다. 서열 번호 39 및 서열 번호 40에 의해 밝혀지고 도 2에 나타낸 바와 같은 이러한 폴리-시스트론 발현 시스템에서, 외피 단백질 E, M 및 S는 RNA-의존성 RNA 폴리머라제를 포함하는 음성 RNA 가닥으로부터 직접 전사된다. 서열 군 A-D의 모든 부류의 외피 단백질이 RNA-의존성으로 발현되지 않는다면, 실시예 1에 기재된 바와 같은 추가 발현 플라스미드는 세포주에서 바이러스 외피의 생명공학적 생산을 위한 외피 단백질의 완전한 세트를 발현하는데 사용될 수 있다. 실시예 2에서, N 단백질을 코딩하는 발현 플라스미드가 이러한 목적을 위해 사용된다(서열 번호 35)(도 2 참조).
플라스미드의 정제, 장쇄 핵산의 형질감염뿐만 아니라, 바이러스 외피의 정제는 대체로 실시예 1에 기재된 공정 순서를 따른다. 그러나, 상기 공정은 서열 번호 39 및 서열 번호 40에 기재된 장쇄 핵산이 형질감염 전에 T7 RNA 폴리머라제에 의해 서열 번호 33 및 서열 번호 34에 따른 상응하는 RNA 형태로 형질전환되는 추가 단계를 포함한다. 이러한 양성 RNA 가닥은 세포주에서 RNA-의존성 RNA 폴리머라제의 생성을 유도하며, 이는 이로부터 음성 RNA 가닥을 생성한다. 이어서, 이러한 음성 RNA 가닥으로부터 메신저 RNA(mRNA)가 전사되고, 이는 바이러스 외피에서 외피 단백질의 생산 및 어셈블리를 유도한다.
이러한 방식으로 생산된 백신은 상응하는 데옥시리보핵산의 유전자 발현을 통해 수득된 외피 단백질에 추가하여, 서열 번호 39 및 서열 번호 40의 T7 전사를 통해 발현되는 완전 합성 장쇄 리보핵산을 함유한다는 점에서 제1 실시예 1에 기재된 백신과 상이하다.
제2 실시예는 N 단백질을 발현하는 헬퍼 세포주에서 스스로 증식하는 바이러스 외피를 생성한다는 점에서 제1 적용예에 비해 이점을 갖는다. 이것은 이와 같이 형성된 바이러스 외피가 RNA-의존성 RNA 폴리머라제와 외피 단백질 E, M, S를 코딩하는 양성 RNA 가닥을 추가로 포함하고 있기 때문에 가능하다. 이러한 바이러스 외피가 세포에 의해 흡수되면, 세포 자체가 자극되어 바이러스 외피를 생성한다. 세포가 N 단백질을 에피솜으로 발현하면, 백신 생산 세포주의 경우처럼 자가 복제 바이러스 외피가 형성된다. 이는 생산 공정을 단순화하고 값비싼 형질감염 시약 없이 수행될 수 있다. 표적 세포가 임의의 N-단백질을 발현하지 않는다면, 바이러스 외피도 이로부터 형성되지만, 이어서 이들은 패키징된 RNA 가닥이 없고 더 이상 자가 복제될 수 없다. 이러한 바이러스 외피는 실시예 1에 나타낸 제조 공정에 의해 생산된 바이러스 외피와 동일한 화학적/물리적 구조 및 동일한 항원성을 갖는다. 실시예 2는 추가의 헬퍼 세포주 및 생산 유기체에서 바이러스 외피, 단편 및 바이러스 외피 단백질의 생산뿐만 아니라, RNA 백신으로서의 직접 적용을 가능하게 한다.
방법:
박테리아 및 효모 균주의 배양
에스케리키아 콜리(이. 콜리) DH5알파는 37℃에서 Luria-Broth(LB)에서 배양되었다. 사카로미세스 세레비시아(Saccharomyces cerevisiae) VL6-48N(Kouprina et al. 2006 Methods in Mol. Biol. 349, 85-101)를 30℃에서 우라실이 없는 효모 펩톤-덱스트로스(YPD) 배지 또는 합성 드롭아웃(SD) 배지에서 배양하였다.
서열 설계 및 드 노보(de-novo) DNA 합성.
모노-시스트론 및 폴리-시스트론 발현 작제물에 대한 DNA 서열은 첨부된 서열 목록(서열 번호 1 내지 40)에 개시된 서열 부분으로부터 어셈블리하였다. 합성 제한은 동의어 코돈 교체 및 유전자간 서열 내에서 원하는 염기 치환의 적용에 의해 계산적으로 제거되었다. 최적의 역합성 어셈블리 경로를 정의하기 위해, 합성-최적화된 DNA 설계는 상업적 공급업체에 의해 저비용 합성에 적합한 더 작은 DNA 단편으로 계층적으로 분할되었다. 분할 전략은 4단계의 계층적 어셈블리 공정으로서 설계되었다. 1.4 kb(킬로베이스) 크기의 하위 블록을 5.4 kb 블록으로 어셈블리하고 16 kb 크기의 세그먼트로 추가로 어셈블리한 다음, 35 내지 40 kb의 최종 COVAX 작제물로 어셈블리하였다. 선형 DNA 어셈블리 부분은 말단에 상동성 중첩을 가지며 3' 프리픽스에서 5' 서픽스 서열이 중첩되어 어셈블리된 DNA 부분을 벡터에 통합하고 최종 COVAX DNA 설계의 계층적 어셈블리를 허용한다. DNA 어셈블리 부분은 서열이 검증된 클론 플라스미드 작제물 및 이중 가닥 선형 DNA로서 저비용 DNA 합성에 의해 상업적 공급업체로부터 입수했다.
모노-시스트론 발현 작제물의 생성:
SARS-2 CoV의 S-단백질, SARS-CoV-2 또는 MHV의 M-단백질, N-단백질 및 E-단백질의 완전한 단백질-코딩 서열을 포함하는 합성 핵산 서열은 서열-검증된 합성 DNA로부터 폴리머라제 증폭 기술(PCR)에 의해 증폭되었다. 개시 코돈 이전의 번역 개시 부위는 올리고뉴클레오티드 프라이머에 의해 도입되었다. PCR 생성물은 이들의 분자량에 따라 아가로스 겔 전기영동으로 분리한 다음, 뉴클레오스핀(nucleospin) 컬럼(NucleoSpin Gel 및 PCR Clean-up Kit, Macherey nail)으로 정제하였다. PCR 생성물은 Topo-TA 클로닝 키트(TOPO-TA 클로닝 키트, ThermoFisher)를 사용하여 pcDNA3.4 벡터에 클로닝되었다. 플라스미드의 분자량은 아가로스 겔 전기영동에 의해 결정되었고(도 3) DNA 서열은 Sanger 시퀀싱에 의해 확인되었다.
폴리-시스트론 COVAX DNA 작제물의 생성:
폴리-시스트론 COVAX DNA 작제물에 대한 DNA 어셈블리 부분은 IIS형 제한 효소(Bbsl, BspQl, Pacl 및 Pmel(New England Biolabs))를 사용한 제한 분해에 의해 플라스미드로부터 방출되었다. 등몰량의 DNA 삽입물(100 ng, 0.115 pmol) 및 선형화된 벡터 pXMCS2(100 ng, 0.038 pmol)를 T5 엑소뉴클레아제, 퓨전 폴리머라제 및 Taq DNA 리가아제와 함께 50℃에서 1시간 동안 인큐베이션하였다. 등온 어셈블리 후, 작제물을 E. coli DH5 알파 세포(BioRad MiniPulser)에 전기천공하였다. 세포를 LB 배지에서 1시간 동안 인큐베이션한 다음, LB 플레이트에 플레이팅하였다. 세그먼트 및 완전한 COVAX 작제물은 리튬 아세테이트 형질전환 방법(Gietz et al 2007, Nature Protocols, 2, 31-34)에 따라 플라스미드 pMR10Y(pMR10::CEN/ARS::URA3, Christen et al. 2015, ACS Synthetic Biology, 4, 927-934)를 사용하여 효모 재조합에 의해 블록으로부터 어셈블리되었다. Saccharomyces cerevisiae VL6-48N을 5 ㎖ YPD에서 밤새 성장시키고 50 ㎖ YPD에 1:20으로 희석하고 4시간 동안 인큐베이션하였다. 1,000 rcf에서 5분 동안 원심분리하여 세포를 수집하고, 25 ㎖의 증류수로 세척하고, 3,000 rcf에서 5분 동안 원심분리하였다. 펠렛을 1 ㎖ 리튬 아세테이트 혼합물(0.1 M 리튬 아세테이트, 0.01 M Tris-HCl, pH 7.5, 0.001 M EDTA, pH 8.0)에 용해시켰다. 다음으로, 100 ㎕ 단일 가닥 연어 정자 DNA(1% w/v 연어 정자 DNA(ssDNA), 0.01 M Tris-HCl, pH 7.5, 0.001 M EDTA, pH 8.0) 및 6 ㎖ PEG-믹스(40% w/v 폴리(에틸렌 글리콜) 3015-3685 g/mol, 0.01 M Tris-HCl, pH 7.5, 0.001 M EDTA, pH 8.0)를 첨가하였다. PEG 세포 믹스로부터 710 ㎕ 분취량을 100 ng의 분해된 DNA 블록 및 250 ng의 선형화된 pMR10Y 벡터(Pad, Pmel)와 조합하였다. 샘플을 30℃에서 30분 동안 인큐베이션하였다. 인큐베이션 후, 70 ㎕ 디메틸 설폭사이드(DMSO)를 첨가하고, 샘플을 42℃에서 15분 동안 열 충격하였다. 세포를 1,000 rcf에서 2분 동안 원심분리하여 수집한 다음, 우라실이 없는 SD 플레이트에 플레이팅하고, 콜로니가 보일 때까지 30℃에서 3일 동안 배양하였다(표 S1 참조).
COVAX DNA 작제물의 서열 검증.
어셈블리된 DNA 작제물의 서열 검증은 Nextera DNA Flex Library Prep-Kit를 사용하여 iSeq 기기(Illumina)에서 수행되었다. ura + 효모 형질전환체의 게놈 DNA는 제조업체에 의해 지정된 태깅 프로토콜에 따라 단편화되고 처리되었다. 서열은 리드(read) 서열로부터 새로 계산되었고 생성된 콘티그는 CLC Genomics Workbench 소프트웨어(Quiagen)를 사용하여 참조 서열과 비교되었다. COVAX191△N 및 COVAX191△HEN의 완전한 어셈블리는 완전히 닫힌 서열 커버리지 플롯으로 확인되었다(도 4).
실시예 3
각각 하나의 원형 서열(바이러스 서열, T7 프로모터 및 폴리A-신호뿐만 아니라 벡터, 모두 하나의 효모 인공 염색체 또는 "YAC"에 함께)을 함유하는 효모 클론을 성장시키고, 수확하고, 이의 YAC를 추출하였다. 이와 같이 얻은 YAC는 제한 효소 Eagl로 절단되어 폴리A-신호 직후에 선형화된 이중 가닥 DNA 분자가 생성되었다. 이러한 DNA 분자를 프로테이나제 K로 표준 처리한 후 트리졸(페놀/클로로포름) 추출로 RNase를 제거한 후, T7 폴리머라제를 사용한 시험관내 전사에 의해 백신 바이러스 게놈에 상응하는 단일 가닥 RNA를 수득하였다. 이와 같이 수득된 RNA를 적합한 세포주(HEK293T 또는 Vero 세포)에 형질감염시켰다. 양성 대조군의 경우, 전장 작제물 "GBsyn_V33" 변경되지 않은 HEK293 또는 Vero 세포는 RNA 게놈의 복제, 서브게놈 mRNA의 생성 및 따라서 바이러스 단백질로의 번역을 지원하였다. 이들은 양성 가닥 RNA 게놈 및 세포막으로부터의 구성요소와 함께, 자손 바이러스를 형성하였으며, 이 경우 야생형 천연 SARS-CoV-2 바이러스를 형성하였다. 결실 돌연변이체의 경우, 바이러스 게놈에서 결실된 유전자 또는 유전자들은 DNA 형태로 세포주에 형질감염되어 단백질 또는 단백질들의 일시적인 발현을 유도하여 자손 바이러스의 생성을 가능하게 하는 데 필요한 결손 인자를 제공한다. 대안적으로 (그리고 바람직하게), 선택 압력 하에서 이러한 세포의 배양은 단백질 또는 단백질들이 지속적으로 발현되는 세포 게놈으로 유전자 또는 유전자들의 안정적인 통합을 유도한다(발현을 통해 본 발명자들은 유전자로부터 mRNA의 생성과 단백질로의 후속 번역을 이해한다). 백신 바이러스 게놈에 없는 유전자로부터 만들어진 단백질을 일시적으로 또는 안정적으로 발현하는 그러한 세포는 구조 단백질의 전체 세트 및 하나 이상의 유전자가 결실된 백신 바이러스 게놈을 특징으로 하는 백신 바이러스의 연속 생산을 가능하게 한다. 이와 같이 얻어진 백신 바이러스는 정화(백신 바이러스로부터 세포 분리), 벤조아제에 의한 DNA 분해, 한외 여과/정용 여과("UF/DF") 및 최종적으로 멸균 여과(0.22 μm 여과)를 특징으로 하는 소위 다운스트림 처리(DSP) 공정에서 정제되었다.
SEQUENCE LISTING <110> Swiss Rockets AG <120> Fully synthetic, long-chain nucleic acid for vaccine production to protect against coronaviruses <130> P6086PC00 <140> EP20020240.6 <141> 2020-05-20 <150> EP20020092.1 <151> 2020-03-03 <160> 59 <170> BiSSAP 1.3.6 <210> 1 <211> 1263 <212> DNA <213> Artificial Sequence <220> <223> COVAX192_N <400> 1 atggtgtctg ataatggacc tcaaaatcag cgaaatgcac ctcgcattac gtttggtgga 60 ccatcagatt caactggcag taaccagaat ggagaacgaa gtggtgcgcg atcaaaacaa 120 cgccgcccgc aaggtttacc caataatact gcgtcttggt tcaccgctct cactcaacat 180 ggcaaggaag atttaaaatt ccctcgagga caaggcgttc caattaacac caatagcagt 240 ccagatgacc aaattggcta ctaccgccgc gccacaagac gaattcgtgg tggtgatggt 300 aaaatgaaag atctcagtcc aagatggtat ttctactatc taggaactgg gccagaagct 360 ggacttcctt atggtgctaa caaagatggc atcatatggg ttgcaactga gggagccttg 420 aatacaccaa aagatcacat tggcaccaga aatcctgcta acaatgctgc aatcgtgcta 480 caacttcctc aaggaacaac attaccaaaa ggtttttacg cagaagggtc tagaggtgga 540 agtcaagcct cttctagatc atcatcacgt agtcgcaaca gttcaagaaa ttcaactcca 600 ggttcaagta gaggaacttc tcctgctaga atggctggaa atggaggtga tgctgctctt 660 gctttgttac tacttgacag attgaaccag cttgagagca aaatgtctgg taaaggccaa 720 caacaacaag gccaaactgt cactaagaaa tctgctgctg aggcttctaa gaagcctaga 780 caaaaacgta ctgccactaa agcatacaat gtaacacaag ctttcggcag acgtggtcca 840 gaacaaactc aaggaaattt tggggatcag gaactaatca gacaaggaac tgattacaaa 900 cattggccgc aaattgcaca atttgctcct tctgcttcag cgttctttgg aatgtcgaga 960 attggaatgg aagtcacacc ttcgggaaca tggttgacct atacaggtgc catcaaattg 1020 gatgacaaag atccaaattt caaagatcaa gtcattttgc tgaataagca tattgacgca 1080 tacaaaacat tcccaccaac agagcctaaa aaggacaaaa agaagaaggc tgatgaaact 1140 caagccttac cgcagagaca gaagaaacag caaactgtga ctcttcttcc tgctgcagat 1200 ttggatgatt tctccaaaca attgcaacaa tccatgagca gtgctgactc aactcaggcc 1260 taa 1263 <210> 2 <211> 420 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Nucleocapsid_Protein_Sars-CoV2 <400> 2 Met Val Ser Asp Asn Gly Pro Gln Asn Gln Arg Asn Ala Pro Arg Ile 1 5 10 15 Thr Phe Gly Gly Pro Ser Asp Ser Thr Gly Ser Asn Gln Asn Gly Glu 20 25 30 Arg Ser Gly Ala Arg Ser Lys Gln Arg Arg Pro Gln Gly Leu Pro Asn 35 40 45 Asn Thr Ala Ser Trp Phe Thr Ala Leu Thr Gln His Gly Lys Glu Asp 50 55 60 Leu Lys Phe Pro Arg Gly Gln Gly Val Pro Ile Asn Thr Asn Ser Ser 65 70 75 80 Pro Asp Asp Gln Ile Gly Tyr Tyr Arg Arg Ala Thr Arg Arg Ile Arg 85 90 95 Gly Gly Asp Gly Lys Met Lys Asp Leu Ser Pro Arg Trp Tyr Phe Tyr 100 105 110 Tyr Leu Gly Thr Gly Pro Glu Ala Gly Leu Pro Tyr Gly Ala Asn Lys 115 120 125 Asp Gly Ile Ile Trp Val Ala Thr Glu Gly Ala Leu Asn Thr Pro Lys 130 135 140 Asp His Ile Gly Thr Arg Asn Pro Ala Asn Asn Ala Ala Ile Val Leu 145 150 155 160 Gln Leu Pro Gln Gly Thr Thr Leu Pro Lys Gly Phe Tyr Ala Glu Gly 165 170 175 Ser Arg Gly Gly Ser Gln Ala Ser Ser Arg Ser Ser Ser Arg Ser Arg 180 185 190 Asn Ser Ser Arg Asn Ser Thr Pro Gly Ser Ser Arg Gly Thr Ser Pro 195 200 205 Ala Arg Met Ala Gly Asn Gly Gly Asp Ala Ala Leu Ala Leu Leu Leu 210 215 220 Leu Asp Arg Leu Asn Gln Leu Glu Ser Lys Met Ser Gly Lys Gly Gln 225 230 235 240 Gln Gln Gln Gly Gln Thr Val Thr Lys Lys Ser Ala Ala Glu Ala Ser 245 250 255 Lys Lys Pro Arg Gln Lys Arg Thr Ala Thr Lys Ala Tyr Asn Val Thr 260 265 270 Gln Ala Phe Gly Arg Arg Gly Pro Glu Gln Thr Gln Gly Asn Phe Gly 275 280 285 Asp Gln Glu Leu Ile Arg Gln Gly Thr Asp Tyr Lys His Trp Pro Gln 290 295 300 Ile Ala Gln Phe Ala Pro Ser Ala Ser Ala Phe Phe Gly Met Ser Arg 305 310 315 320 Ile Gly Met Glu Val Thr Pro Ser Gly Thr Trp Leu Thr Tyr Thr Gly 325 330 335 Ala Ile Lys Leu Asp Asp Lys Asp Pro Asn Phe Lys Asp Gln Val Ile 340 345 350 Leu Leu Asn Lys His Ile Asp Ala Tyr Lys Thr Phe Pro Pro Thr Glu 355 360 365 Pro Lys Lys Asp Lys Lys Lys Lys Ala Asp Glu Thr Gln Ala Leu Pro 370 375 380 Gln Arg Gln Lys Lys Gln Gln Thr Val Thr Leu Leu Pro Ala Ala Asp 385 390 395 400 Leu Asp Asp Phe Ser Lys Gln Leu Gln Gln Ser Met Ser Ser Ala Asp 405 410 415 Ser Thr Gln Ala 420 <210> 3 <211> 1368 <212> DNA <213> Artificial Sequence <220> <223> COVAX191_N <400> 3 atggtgtctt ttgttcctgg gcaagaaaat gccggtggca gaagctcctc tgtaaaccgc 60 gctggtaatg gaatcctcaa gaaaaccact tgggctgacc aaaccgagcg tggaccaaat 120 aatcaaaata gaggcagaag gaatcagcca aagcagactg caactactca acccaactcc 180 gggagtgtgg ttccccatta ctcctggttt tctggcatta cccagttcca aaagggaaag 240 gagtttcagt ttgcagaagg acaaggagtg cctattgcca atggaatccc cgcttcagag 300 caaaagggat attggtatag acacaaccgc cgttctttta aaacacctga tgggcagcag 360 aagcaattac tgcccagatg gtatttttac tatcttggca cagggcccca tgctggagcc 420 agttatggag acagcattga aggcgtcttt tgggttgcaa acagccaagc ggacaccaat 480 acccgctctg atattgtcga aagggaccca agcagtcatg aggctattcc tactaggttt 540 gcgcccggca cggtattgcc tcagggcttt tatgttgaag gctctggaag gtctgccccg 600 gccagccgat ctggttcgcg gtcacaatcc cgtgggccaa ataatcgcgc tagaagcagt 660 tccaaccagc gccagcctgc ctctactgta aaacctgata tggccgaaga aattgctgct 720 cttgttttgg ctaagctcgg taaagatgcc ggccagccca agcaagtaac gaagcaaagt 780 gccaaagaag tcaggcagaa aattttaaac aagcctcgcc aaaagaggac tccaaacaag 840 cagtgcccag tgcagcagtg ttttggaaag agaggcccca atcagaattt tggaggctct 900 gaaatgttaa aacttggaac tagtgatcca cagttcccca ttcttgcaga gttggctcca 960 acagttggtg ccttcttctt tggatctaaa ttagaattgg tcaaaaagaa ttctggtggt 1020 gctgatgaac ccaccaaaga tgtgtatgag ctgcaatatt caggtgcagt tagatttgat 1080 agtactctac ctggttttga gactatcatg aaagtgttga atgagaattt gaatgcctac 1140 cagaaggatg gtggtgcaga tgtggtgagc ccaaagcccc aaagaaaagg gcgtagacag 1200 gctcaggaaa agaaagatga agtagataat gtaagcgttg caaagcccaa aagctctgtg 1260 cagcgaaatg taagtagaga attaacccca gaggatagaa gtctgttggc tcagatcctt 1320 gatgatggcg tagtgccaga tgggttagaa gatgactcta atgtgtaa 1368 <210> 4 <211> 455 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Nucleocapsid_Protein_MHV <400> 4 Met Val Ser Phe Val Pro Gly Gln Glu Asn Ala Gly Gly Arg Ser Ser 1 5 10 15 Ser Val Asn Arg Ala Gly Asn Gly Ile Leu Lys Lys Thr Thr Trp Ala 20 25 30 Asp Gln Thr Glu Arg Gly Pro Asn Asn Gln Asn Arg Gly Arg Arg Asn 35 40 45 Gln Pro Lys Gln Thr Ala Thr Thr Gln Pro Asn Ser Gly Ser Val Val 50 55 60 Pro His Tyr Ser Trp Phe Ser Gly Ile Thr Gln Phe Gln Lys Gly Lys 65 70 75 80 Glu Phe Gln Phe Ala Glu Gly Gln Gly Val Pro Ile Ala Asn Gly Ile 85 90 95 Pro Ala Ser Glu Gln Lys Gly Tyr Trp Tyr Arg His Asn Arg Arg Ser 100 105 110 Phe Lys Thr Pro Asp Gly Gln Gln Lys Gln Leu Leu Pro Arg Trp Tyr 115 120 125 Phe Tyr Tyr Leu Gly Thr Gly Pro His Ala Gly Ala Ser Tyr Gly Asp 130 135 140 Ser Ile Glu Gly Val Phe Trp Val Ala Asn Ser Gln Ala Asp Thr Asn 145 150 155 160 Thr Arg Ser Asp Ile Val Glu Arg Asp Pro Ser Ser His Glu Ala Ile 165 170 175 Pro Thr Arg Phe Ala Pro Gly Thr Val Leu Pro Gln Gly Phe Tyr Val 180 185 190 Glu Gly Ser Gly Arg Ser Ala Pro Ala Ser Arg Ser Gly Ser Arg Ser 195 200 205 Gln Ser Arg Gly Pro Asn Asn Arg Ala Arg Ser Ser Ser Asn Gln Arg 210 215 220 Gln Pro Ala Ser Thr Val Lys Pro Asp Met Ala Glu Glu Ile Ala Ala 225 230 235 240 Leu Val Leu Ala Lys Leu Gly Lys Asp Ala Gly Gln Pro Lys Gln Val 245 250 255 Thr Lys Gln Ser Ala Lys Glu Val Arg Gln Lys Ile Leu Asn Lys Pro 260 265 270 Arg Gln Lys Arg Thr Pro Asn Lys Gln Cys Pro Val Gln Gln Cys Phe 275 280 285 Gly Lys Arg Gly Pro Asn Gln Asn Phe Gly Gly Ser Glu Met Leu Lys 290 295 300 Leu Gly Thr Ser Asp Pro Gln Phe Pro Ile Leu Ala Glu Leu Ala Pro 305 310 315 320 Thr Val Gly Ala Phe Phe Phe Gly Ser Lys Leu Glu Leu Val Lys Lys 325 330 335 Asn Ser Gly Gly Ala Asp Glu Pro Thr Lys Asp Val Tyr Glu Leu Gln 340 345 350 Tyr Ser Gly Ala Val Arg Phe Asp Ser Thr Leu Pro Gly Phe Glu Thr 355 360 365 Ile Met Lys Val Leu Asn Glu Asn Leu Asn Ala Tyr Gln Lys Asp Gly 370 375 380 Gly Ala Asp Val Val Ser Pro Lys Pro Gln Arg Lys Gly Arg Arg Gln 385 390 395 400 Ala Gln Glu Lys Lys Asp Glu Val Asp Asn Val Ser Val Ala Lys Pro 405 410 415 Lys Ser Ser Val Gln Arg Asn Val Ser Arg Glu Leu Thr Pro Glu Asp 420 425 430 Arg Ser Leu Leu Ala Gln Ile Leu Asp Asp Gly Val Val Pro Asp Gly 435 440 445 Leu Glu Asp Asp Ser Asn Val 450 455 <210> 5 <211> 231 <212> DNA <213> Artificial Sequence <220> <223> COVAX192_E <400> 5 atggtgtact cattcgtttc ggaagagaca ggtacgttaa tagttaatag cgtacttctt 60 tttcttgctt tcgtggtatt cttgctagtt acactagcca ttcttactgc gcttcgattg 120 tgtgcgtact gttgcaatat tgttaacgtg agtcttgtaa aaccttcttt ttacgtttac 180 tctcgtgtta aaaatctgaa ttcttctcgg gttcctgatc ttctggtcta a 231 <210> 6 <211> 76 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Envelope_Protein_Sars-CoV2 <400> 6 Met Val Tyr Ser Phe Val Ser Glu Glu Thr Gly Thr Leu Ile Val Asn 1 5 10 15 Ser Val Leu Leu Phe Leu Ala Phe Val Val Phe Leu Leu Val Thr Leu 20 25 30 Ala Ile Leu Thr Ala Leu Arg Leu Cys Ala Tyr Cys Cys Asn Ile Val 35 40 45 Asn Val Ser Leu Val Lys Pro Ser Phe Tyr Val Tyr Ser Arg Val Lys 50 55 60 Asn Leu Asn Ser Ser Arg Val Pro Asp Leu Leu Val 65 70 75 <210> 7 <211> 255 <212> DNA <213> Artificial Sequence <220> <223> COVAX191_E <400> 7 atggtgttta atttattcct tacagacaca gtatggtatg tggggcagat tatttttata 60 ttcgcagtgt gtttgatggt caccataatt gtggttgcct tccttgcgtc tatcaaactt 120 tgtattcaac tttgcggttt atgtaatact ttggtgctgt ccccttctat ttatttgtat 180 gataggagta agcagcttta taagtactat aatgaagaaa tgagactgcc cctattagag 240 gtggatgata tctaa 255 <210> 8 <211> 84 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Envelope_Protein_MHV <400> 8 Met Val Phe Asn Leu Phe Leu Thr Asp Thr Val Trp Tyr Val Gly Gln 1 5 10 15 Ile Ile Phe Ile Phe Ala Val Cys Leu Met Val Thr Ile Ile Val Val 20 25 30 Ala Phe Leu Ala Ser Ile Lys Leu Cys Ile Gln Leu Cys Gly Leu Cys 35 40 45 Asn Thr Leu Val Leu Ser Pro Ser Ile Tyr Leu Tyr Asp Arg Ser Lys 50 55 60 Gln Leu Tyr Lys Tyr Tyr Asn Glu Glu Met Arg Leu Pro Leu Leu Glu 65 70 75 80 Val Asp Asp Ile <210> 9 <211> 672 <212> DNA <213> Artificial Sequence <220> <223> COVAX192_M <400> 9 atggtggcag attccaacgg tactattacc gttgaggagc tgaaaaagct ccttgaacaa 60 tggaacctag taataggttt cctattcctt acatggattt gcctgctgca atttgcctat 120 gccaacagga ataggttttt gtacatcatt aagttgattt tcctctggct gttatggcca 180 gtaactttag cttgttttgt gcttgctgct gtttacagaa taaattggat caccggtgga 240 attgctattg caatggcttg tcttgtagga ttgatgtggc taagctactt cattgcttct 300 ttcagactgt ttgcgcgtac gcgttccatg tggtcattca atccagaaac taacattctt 360 ctcaacgtgc cactccatgg aactattctg actagaccgc ttctagaaag tgaactcgta 420 atcggagctg ttatccttcg tggacatctt cgtattgctg gacatcatct aggacgctgt 480 gacatcaagg atctacctaa agaaatcact gttgctacat cacgaacgct ttcttattac 540 aaattgggag cttcacagcg tgtagcaggt gattcaggtt ttgctgcata tagtcgctac 600 aggattggca actataaatt aaacacagac cattccagta gcagtgacaa tattgctttg 660 cttgtacagt aa 672 <210> 10 <211> 223 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Membrane_Protein_Sars-CoV2 <400> 10 Met Val Ala Asp Ser Asn Gly Thr Ile Thr Val Glu Glu Leu Lys Lys 1 5 10 15 Leu Leu Glu Gln Trp Asn Leu Val Ile Gly Phe Leu Phe Leu Thr Trp 20 25 30 Ile Cys Leu Leu Gln Phe Ala Tyr Ala Asn Arg Asn Arg Phe Leu Tyr 35 40 45 Ile Ile Lys Leu Ile Phe Leu Trp Leu Leu Trp Pro Val Thr Leu Ala 50 55 60 Cys Phe Val Leu Ala Ala Val Tyr Arg Ile Asn Trp Ile Thr Gly Gly 65 70 75 80 Ile Ala Ile Ala Met Ala Cys Leu Val Gly Leu Met Trp Leu Ser Tyr 85 90 95 Phe Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser 100 105 110 Phe Asn Pro Glu Thr Asn Ile Leu Leu Asn Val Pro Leu His Gly Thr 115 120 125 Ile Leu Thr Arg Pro Leu Leu Glu Ser Glu Leu Val Ile Gly Ala Val 130 135 140 Ile Leu Arg Gly His Leu Arg Ile Ala Gly His His Leu Gly Arg Cys 145 150 155 160 Asp Ile Lys Asp Leu Pro Lys Glu Ile Thr Val Ala Thr Ser Arg Thr 165 170 175 Leu Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp Ser 180 185 190 Gly Phe Ala Ala Tyr Ser Arg Tyr Arg Ile Gly Asn Tyr Lys Leu Asn 195 200 205 Thr Asp His Ser Ser Ser Ser Asp Asn Ile Ala Leu Leu Val Gln 210 215 220 <210> 11 <211> 690 <212> DNA <213> Artificial Sequence <220> <223> COVAX191_M <400> 11 atggtgagta gtactactca ggccccagag cccgtctatc aatggaccgc cgacgaggca 60 gttcaattcc ttaaggaatg gaacttctcg ttgggcatta tactactctt tattactatc 120 atactacagt tcggttacac gagccgtagc atgtttattt atgttgtgaa aatgataatc 180 ttgtggttaa tgtggccact gactattgtt ttgtgtattt tcaattgcgt gtatgcgcta 240 aataatgtgt atcttggatt ttctatagtg tttactatag tgtccattgt aatctggatc 300 atgtattttg tgaacagcat aaggttgttt atcaggactg gtagctggtg gagcttcaac 360 cccgaaacaa acaaccttat gtgtatagat atgaaaggta ccgtgtatgt tagacccatt 420 attgaggatt accatacact aacagccact attattcgtg gccacctcta catgcaaggt 480 gttaagctag gcaccggttt ctctttgtct gacttgcccg cttatgttac agttgctaag 540 gtgtcacacc tttgcactta taagcgcgca ttcttagaca aggtagacgg tgttagcggt 600 tttgctgttt atgtgaagtc caaggtcgga aattaccgac tgccctcaaa caaaccgagt 660 ggcgcggaca ccgcattgtt gagaacctaa 690 <210> 12 <211> 229 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Membrane_Protein_MHV <400> 12 Met Val Ser Ser Thr Thr Gln Ala Pro Glu Pro Val Tyr Gln Trp Thr 1 5 10 15 Ala Asp Glu Ala Val Gln Phe Leu Lys Glu Trp Asn Phe Ser Leu Gly 20 25 30 Ile Ile Leu Leu Phe Ile Thr Ile Ile Leu Gln Phe Gly Tyr Thr Ser 35 40 45 Arg Ser Met Phe Ile Tyr Val Val Lys Met Ile Ile Leu Trp Leu Met 50 55 60 Trp Pro Leu Thr Ile Val Leu Cys Ile Phe Asn Cys Val Tyr Ala Leu 65 70 75 80 Asn Asn Val Tyr Leu Gly Phe Ser Ile Val Phe Thr Ile Val Ser Ile 85 90 95 Val Ile Trp Ile Met Tyr Phe Val Asn Ser Ile Arg Leu Phe Ile Arg 100 105 110 Thr Gly Ser Trp Trp Ser Phe Asn Pro Glu Thr Asn Asn Leu Met Cys 115 120 125 Ile Asp Met Lys Gly Thr Val Tyr Val Arg Pro Ile Ile Glu Asp Tyr 130 135 140 His Thr Leu Thr Ala Thr Ile Ile Arg Gly His Leu Tyr Met Gln Gly 145 150 155 160 Val Lys Leu Gly Thr Gly Phe Ser Leu Ser Asp Leu Pro Ala Tyr Val 165 170 175 Thr Val Ala Lys Val Ser His Leu Cys Thr Tyr Lys Arg Ala Phe Leu 180 185 190 Asp Lys Val Asp Gly Val Ser Gly Phe Ala Val Tyr Val Lys Ser Lys 195 200 205 Val Gly Asn Tyr Arg Leu Pro Ser Asn Lys Pro Ser Gly Ala Asp Thr 210 215 220 Ala Leu Leu Arg Thr 225 <210> 13 <211> 3885 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 S <400> 13 atggtgtttg tttttcttgt tttattgcca ctagtctcta gtcagtgtgt taatcttaca 60 atggtgtttg tttttcttgt tttattgcca ctagtctcta gtcagtgtgt taatcttaca 120 accagaactc aattaccccc tgcatacact aattctttca cacgtggtgt ttattaccct 180 gacaaagttt tcagatcctc agttttacat tcaactcagg acttgttctt acctttcttt 240 tccaatgtta cttggttcca tgctatacat gtctctggga ccaatggtac taagaggttt 300 gataaccctg tcctaccatt taatgatggt gtttactttg cttccactga gaagtctaac 360 ataataagag gctggatttt tggtactact ttagattcga aaacccagtc cctacttatt 420 gttaataacg ctactaatgt tgttatcaaa gtctgtgaat ttcaattttg taacgatcca 480 tttttgggtg tttattacca caaaaacaac aaaagttgga tggaaagtga gttcagagtt 540 tattctagtg cgaataattg cacttttgaa tacgtctctc agccttttct tatggacctt 600 gaaggaaaac agggtaattt caaaaatctt agggaatttg tgttcaagaa tattgatggt 660 tacttcaaga tatactctaa gcacacgcct attaatttag tgcgtgatct ccctcagggt 720 ttttcggctt tagaaccatt ggtagatttg ccaataggta ttaacatcac taggtttcaa 780 actttacttg ctttacatag aagttattta actcctggtg attcttcttc aggttggaca 840 gctggtgctg cagcttatta tgtgggttat cttcaaccta ggacttttct actgaagtac 900 aatgaaaatg gaaccattac agatgctgta gactgtgcac ttgaccctct ctcagaaaca 960 aagtgtacgt tgaaatcctt cactgtagaa aaaggaatct atcaaacttc taactttaga 1020 gtccaaccaa cagaatctat tgttagattt cctaacatca caaacttgtg cccttttggt 1080 gaagttttta acgccaccag atttgcatct gtttatgctt ggaacaggaa gagaatcagc 1140 aactgtgttg ctgattattc tgtcctgtat aattccgcat cattttccac ttttaagtgt 1200 tatggagtgt ctcctactaa attaaatgat ctctgcttta ctaatgtcta tgcagattca 1260 tttgtaatta gaggtgatga agtcagacaa atcgctccag ggcaaactgg aaagattgct 1320 gattataact acaaattacc agatgatttt acaggctgcg ttatagcttg gaattctaac 1380 aatcttgatt ctaaggttgg tggtaattat aattacctgt acagattgtt taggaagtct 1440 aatctcaaac cttttgagag agatatttca actgaaatct atcaggccgg tagcacacct 1500 tgtaatggtg ttgaaggttt taattgttac tttcctctgc aatcatatgg tttccaaccc 1560 actaatggtg ttggttacca accatacaga gtagtagtac tttcttttga acttctacat 1620 gcaccagcaa ctgtttgtgg acctaaaaag tctactaatt tggttaagaa caagtgtgtc 1680 aatttcaact tcaatggttt aacaggcaca ggtgttctta ctgagtctaa caaaaagttt 1740 ctgcctttcc aacaatttgg cagagacatt gctgacacta ctgatgctgt tcgtgatcca 1800 caaacacttg agattcttga cattacacca tgttcttttg gtggtgtcag tgttataaca 1860 ccaggaacaa atacttctaa ccaggttgct gttctttatc aggatgttaa ctgcacagaa 1920 gtccctgttg ctattcatgc agatcaactt actcctactt ggcgtgttta ttctacaggt 1980 tctaatgttt ttcaaacacg tgcaggctgt ttaatagggg ctgaacatgt caacaactca 2040 tatgagtgtg acatacccat tggtgcaggt atatgcgcta gttatcagac tcagactaat 2100 tctcctcgga gagcaagaag tgtagctagt caatccatca ttgcctacac tatgtcactt 2160 ggtgcagaaa attcagttgc ttactctaat aactctattg ccatacccac aaattttact 2220 attagcgtta ccacagaaat tctaccagtg tctatgacca agacatcagt agattgtaca 2280 atgtacattt gtggtgattc aactgaatgc agcaatcttt tgttgcaata tggcagtttt 2340 tgtacacaat taaaccgtgc tttaactgga atagctgttg aacaagacaa aaacacccaa 2400 gaagtttttg cacaagtcaa acaaatttac aagacaccac caattaaaga ttttggcggt 2460 tttaatttta gccagatact gccagatcca tcaaaaccaa gcaagaggtc atttattgaa 2520 gatctactgt tcaacaaagt gacacttgca gatgctggct tcatcaaaca atatggtgat 2580 tgccttggtg atattgctgc tagagacctc atttgtgcac aaaagtttaa cggccttact 2640 gttttgccac ctttgctcac agatgaaatg attgctcaat acacttctgc actgttagca 2700 ggtacaatca cttctggttg gacttttggt gcaggtgctg cattacaaat accatttgct 2760 atgcaaatgg cttataggtt taatggtatt ggagttacac agaatgttct ctatgagaac 2820 caaaaattga ttgccaacca atttaatagt gctattggca aaattcaaga ctcactttct 2880 tccacagcaa gtgcacttgg aaaacttcaa gatgtggtca accaaaatgc acaagcttta 2940 aacacgcttg ttaaacaact tagctccaat tttggtgcaa tttcaagtgt tttaaacgac 3000 atcctttcac gtcttgacaa agttgaggct gaagtgcaaa ttgataggtt gatcacaggc 3060 agacttcaaa gtttgcagac atatgtgact caacaattaa ttagagctgc agaaatcaga 3120 gcttctgcta atcttgctgc tactaaaatg tcagagtgtg tacttggaca atcaaaaaga 3180 gttgactttt gcggaaaggg ctatcatctt atgtcatttc ctcagtcagc acctcatggt 3240 gtcgtctttt tgcatgtgac ttatgtccct gcacaagaaa agaacttcac aactgctcct 3300 gccatttgtc atgatggaaa agcacacttt cctcgtgaag gtgtctttgt ttcaaatggc 3360 acacactggt ttgtaacaca aaggaatttt tatgaaccac aaatcattac tacagacaac 3420 acatttgtgt ctggtaactg tgatgttgta ataggaattg tcaacaacac agtttatgat 3480 cctttgcaac ctgaattaga ctcattcaag gaggagcttg ataaatactt caagaaccat 3540 acctcaccag atgttgattt aggtgacatc tctggcatta atgcttcagt tgtaaacatt 3600 cagaaagaaa tcgaccgcct caatgaggtt gccaagaatt taaatgaatc tctcatcgat 3660 ctccaagaac ttggaaagta tgagcagtat ataaaatggc catggtacat ttggctaggt 3720 tttatagctg gcttgattgc catagtaatg gtgacaatta tgctttgctg tatgaccagt 3780 tgctgtagtt gtctcaaggg ctgttgttct tgtggatcct gctgcaaatt tgacgaggac 3840 gactctgagc cagtgctcaa aggagtcaaa ttacattaca cataa 3885 <210> 14 <211> 1274 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Spike_Protein_Sars-CoV2 <400> 14 Met Val Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys 1 5 10 15 Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser 20 25 30 Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val 35 40 45 Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr 50 55 60 Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe 65 70 75 80 Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr 85 90 95 Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp 100 105 110 Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val 115 120 125 Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val 130 135 140 Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val 145 150 155 160 Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe 165 170 175 Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu 180 185 190 Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His 195 200 205 Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu 210 215 220 Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln 225 230 235 240 Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser 245 250 255 Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln 260 265 270 Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp 275 280 285 Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu 290 295 300 Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg 305 310 315 320 Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 325 330 335 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr 340 345 350 Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 355 360 365 Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 370 375 380 Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser 385 390 395 400 Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 405 410 415 Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly 420 425 430 Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly 435 440 445 Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro 450 455 460 Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro 465 470 475 480 Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr 485 490 495 Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val 500 505 510 Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro 515 520 525 Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe 530 535 540 Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe 545 550 555 560 Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala 565 570 575 Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser 580 585 590 Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln 595 600 605 Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala 610 615 620 Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly 625 630 635 640 Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His 645 650 655 Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys 660 665 670 Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val 675 680 685 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn 690 695 700 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 705 710 715 720 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 725 730 735 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 740 745 750 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 755 760 765 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 770 775 780 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 785 790 795 800 Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg 805 810 815 Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala 820 825 830 Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg 835 840 845 Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro 850 855 860 Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala 865 870 875 880 Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln 885 890 895 Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val 900 905 910 Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe 915 920 925 Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser 930 935 940 Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu 945 950 955 960 Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser 965 970 975 Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val 980 985 990 Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr 995 1000 1005 Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg 1025 1030 1035 1040 Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1045 1050 1055 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln 1060 1065 1070 Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala 1075 1080 1085 His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe 1090 1095 1100 Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn 1105 1110 1115 1120 Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn 1125 1130 1135 Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1140 1145 1150 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1155 1160 1165 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile 1170 1175 1180 Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1185 1190 1195 1200 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr 1205 1210 1215 Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1220 1225 1230 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys 1235 1240 1245 Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <210> 15 <211> 21746 <212> DNA <213> Artificial Sequence <220> <223> COVAX_Syn_RepA56 <400> 15 gtataagagt gattggcgtc cgtacgtacc ctctcaactc taaaactctt gtagtttaaa 60 tctaatctaa actttataaa cggcacttcc tgcgtgtcca tgcccgcggg cctggtcttg 120 tcatagtgct gacatttgta gttccttgac tttcgttctc tgccagtgac gtgtccattc 180 ggcgccagca gcccacccat aggttgcata atggcaaaga tgggcaaata cggcctgggc 240 ttcaaatggg ccccagaatt tccatggatg cttccgaacg catcggagaa gttgggtaac 300 cctgagaggt cagaggagga tgggttttgc ccctctgctg cgcaagaacc gaaagttaaa 360 ggaaaaactt tggttaatca cgtgagggtg aattgtagcc ggcttccagc tttggaatgc 420 tgtgttcagt ctgccataat ccgtgatatt tttgtagatg aggatcccca gaaggtggag 480 gcctcaacta tgatggcatt gcagttcggt agtgccgtct tggttaagcc atccaagcgc 540 ttgtctattc aggcatggac taatttgggt gtgcttccca aaacagctgc catggggttg 600 ttcaagcgcg tctgcctgtg taacaccagg gagtgctctt gtgacgccca cgtggccttt 660 caccttttta cggtccaacc cgatggtgta tgcctgggta atggccgttt tataggctgg 720 ttcgttccag tcacagccat accggagtat gcgaagcagt ggttgcaacc ctggtccatc 780 cttcttcgta agggtggtaa caaagggtct gtgacatccg gccacttccg ccgcgctgtt 840 accatgcctg tgtatgactt taatgtagag gatgcttgtg aggaggttca tcttaacccg 900 aagggtaagt actcctgcaa ggcgtatgcc ctgctgaagg gctatcgcgg tgttaagccc 960 atcctgtttg tggaccagta tggttgcgac tatactggat gtctcgccaa gggtcttgag 1020 gactatggcg atctcacctt gagtgagatg aaggagttgt tccctgtgtg gcgtgactcc 1080 ttggatagtg aagtccttgt ggcttggcac gttgatcgag atcctcgggc tgctatgcgt 1140 ctgcagactc ttgctactgt acgttgcatt gattatgtgg gccaaccgac cgaggatgtg 1200 gtggatggag atgtggtagt gcgtgagcct gctcatcttc tcgcagccaa tgccattgtt 1260 aaaagactcc cccgtttggt ggagactatg ctgtatacgg attcgtccgt tacagaattc 1320 tgttataaaa ccaagctgtg tgaatgcggt tttatcacgc agtttggcta tgtggattgt 1380 tgtggtgaca cctgtgattt tcgtgggtgg gttgccggca atatgatgga tggctttcca 1440 tgtccagggt gtaccaaaaa ttatatgccc tgggaattgg aggcccagtc atcaggtgtt 1500 ataccagaag gaggtgttct attcactcag agcactgata cagtgaatcg tgagtccttt 1560 aagctctacg gtcatgctgt tgtgcctttt ggttctgctg tgtattggag cccttgccca 1620 ggtatgtggc ttccagtaat ttggtcgtcg gttaagtcat actctggttt gacttataca 1680 ggagtagttg gttgtaaggc aattgttcaa gagacagacg ctatatgtcg ttctctgtat 1740 atggattatg tccagcacaa gtgtggcaat ctcgagcaga gagctatcct tggattggac 1800 gatgtctatc atagacagtt gcttgtgaat aggggtgact atagtctcct ccttgagaat 1860 gtggatttgt ttgttaagcg gcgcgctgaa tttgcttgca aattcgccac ctgtggagat 1920 ggtcttgtac ccctcctact agatggttta gtgccccgca gttattattt gattaagagt 1980 ggtcaagctt tcacctctat gatggttaat tttagccatg aggtgactga catgtgtatg 2040 gacatggctt tattgttcat gcatgatgtt aaagtggcca ctaagtatgt taagaaggtt 2100 actggcaaac tggccgtgcg ctttaaagcg ttgggtgtag ccgttgtcag aaaaattact 2160 gaatggtttg atttagccgt ggacattgct gctagtgccg ctggatggct ttgctaccag 2220 ctggtaaatg gcttatttgc agtggccaat ggtgttataa cctttgtaca ggaggtgcct 2280 gagcttgtca agaattttgt tgacaagttc aaggcatttt tcaaggtttt gatcgactct 2340 atgtcggttt ctatcttgtc tggacttact gttgtcaaga ctgcctcaaa tagggtgtgt 2400 cttgctggca gtaaggttta tgaagttgtg cagaaatctt tgtctgcata tgttatgcct 2460 gtgggttgca gcgaagccac ttgtttggtg ggtgagattg aacctgcagt ttttgaagat 2520 gatgttgttg atgtggttaa agccccatta acatatcaag gctgttgtaa gccacccact 2580 tctttcgaga agatttgtat tgtggataaa ttgtatatgg ccaagtgtgg tgatcaattt 2640 taccctgtgg ttgttgataa cgacactgtt ggcgtgttag atcagtgctg gaggtttccc 2700 tgtgcgggca agaaagtcga gtttaacgac aagcccaaag tcaggaagat accctccacc 2760 cgtaagatta agatcacctt cgcactggat gcgacctttg atagtgttct ttcgaaggcg 2820 tgttcagagt ttgaagttga taaagatgtt acattggatg agctgcttga tgttgtgctt 2880 gacgcagttg agagtacgct cagcccttgt aaggagcatg atgtgatagg cacaaaagtt 2940 tgtgctttac ttgataggtt ggcaggagat tatgtctatc tttttgatga gggaggcgat 3000 gaagtgatcg ccccgaggat gtattgttcc ttttctgctc ctgatgacga ggactgcgtt 3060 gcagcggatg ttgtagatgc agatgaaaac caagatgatg atgccgagga ctcagcagtc 3120 cttgtcgctg atacccaaga agaggacggc gttgccaagg ggcaggttga ggcggattcg 3180 gaaatttgcg ttgcgcatac tggtagtcaa gaagaattgg ctgagcctga tgctgtcgga 3240 tctcaaactc ccatcgcctc tgctgaggaa accgaagtcg gagaggcaag cgacagggaa 3300 gggattgctg aggcgaaggc aactgtgtgt gctgatgctg tagatgcctg ccccgatcaa 3360 gtggaggcat ttgaaattga aaaggtcgag gactctatct tggatgagct tcaaactgaa 3420 cttaatgcgc cagcggacaa gacctatgag gatgtcttgg cattcgatgc cgtatgctca 3480 gaggcgttgt ctgcattcta tgctgtgccg agtgatgaga cgcactttaa agtgtgtgga 3540 ttctattcgc ctgctataga gcgcactaat tgttggctgc gttctacttt gatagtaatg 3600 cagagtctac ctttggaatt taaagacttg gagatgcaaa agctctggtt gtcttacaag 3660 gccggctatg accaatgctt tgtggacaaa ctagttaaga gcgtgcccaa gtctattatc 3720 cttccacaag gtggttatgt ggcagatttt gcctatttct ttctaagcca gtgtagcttt 3780 aaagcttatg ctaactggcg ttgtttagag tgtgacatgg agttaaagct tcaaggcttg 3840 gacgccatgt ttttctatgg ggacgttgtg tctcatatgt gcaagtgtgg taatagcatg 3900 accttgttgt ctgcagatat accctacact ttgcattttg gagtgcgaga tgataagttt 3960 tgcgcttttt acacgccaag aaaggtcttt agggctgctt gtgcggtaga tgttaatgat 4020 tgtcactcta tggctgtagt agagggcaag caaattgatg gtaaagtggt taccaaattt 4080 attggtgaca aatttgattt tatggtgggt tacgggatga catttagtat gtctcctttt 4140 gaactcgccc agttatatgg ttcatgtata acaccaaatg tttgttttgt taaaggagat 4200 gttataaagg ttgttcgctt agttaatgct gaagtcattg ttaaccctgc taatgggcgt 4260 atggctcatg gtgccggcgt cgccggcgcc atagctgaaa aggcgggcag tgcttttatt 4320 aaagaaacct ccgatatggt gaaggctcag ggcgtttgcc aggttggtga atgctatgaa 4380 tctgccggtg gtaagttatg taaaaaggtg cttaacattg tagggccaga tgcgcgaggg 4440 catggcaagc aatgctattc acttttagag cgtgcttatc agcatattaa taagtgtgac 4500 aatgttgtca ctactttaat ttcggctggt atatttagtg tgcctactga tgtctcccta 4560 acttacttac ttggtgtagt gacaaagaat gtcattcttg tcagtaacaa ccaggatgat 4620 tttgatgtga tagagaagtg tcaggtgacc tccgttgctg gtaccaaagc gctatcactt 4680 caattggcca aaaatttgtg ccgtgatgta aagtttgtga cgaatgcatg tagttcgctt 4740 tttagtgaat cttgctttgt ctcaagctat gatgtgttgc aggaagttga agcgctgcga 4800 catgatatac aattggatga tgatgctcgt gtctttgtgc aggctaatat ggactgtctg 4860 cccacagact ggcgtctcgt taacaaattt gatagtgttg atggtgttag aaccattaag 4920 tattttgaat gcccgggcgg gatttttgta tccagccagg gcaaaaagtt tggttatgtt 4980 cagaatggtt catttaagga ggcgagtgtt agccaaataa gggctttact cgctaataag 5040 gttgatgtct tgtgtactgt tgatggtgtt aacttccgct cctgctgcgt agcagagggt 5100 gaagtttttg gcaagacatt aggttcagtc ttttgtgatg gcataaatgt caccaaagtt 5160 aggtgtagtg ccatttacaa gggtaaggtt ttctttcagt acagtgattt gtccgaggca 5220 gatcttgtgg ctgttaaaga tgcctttggt tttgatgaac cacaactgct gaagtactac 5280 actatgcttg gcatgtgtaa gtggccagta gttgtttgtg gcaattattt tgctttcaag 5340 cagtcaaata ataattgcta catcaacgtg gcatgtttaa tgctgcaaca cttgagttta 5400 aagtttccta agtggcaatg gcaagaggct tggaacgagt tccgctctgg taaaccacta 5460 aggtttgtgt ccttggtatt agcaaagggc agctttaaat ttaatgaacc ttctgattct 5520 atcgatttta tgcgtgtggt gctacgtgaa gcagatttga gtggtgccac gtgcaatttg 5580 gaatttgttt gtaaatgtgg tgtgaagcaa gagcagcgca aaggtgttga cgctgttatg 5640 cattttggta cgttggataa aggtgatctt gtcaggggtt ataatatcgc atgtacgtgc 5700 ggtagtaaac ttgtgcattg cacccaattt aacgtaccat ttttaatttg ctccaacaca 5760 ccagagggta ggaaactgcc cgacgatgtt gttgcagcta atatttttac tggtggtagt 5820 gtgggccatt acacgcatgt gaaatgtaaa cccaagtacc agctttatga tgcttgtaat 5880 gttaataagg tttcggaggc taagggtaat tttaccgatt gcctctacct taaaaattta 5940 aagcaaacct tctcgtctgt gctgacgact ttttatttag atgacgtaaa gtgtgtggag 6000 tataagccag atttatcgca gtattactgt gagtctggta aatattatac aaaacccatt 6060 attaaggccc aatttagaac atttgagaag gttgatggtg tctataccaa ctttaaattg 6120 gtgggacata gtattgctga aaaactcaat gctaagctgg gatttgattg taattctccc 6180 tttgtggagt ataaaattac agagtggcca acagctactg gagatgtggt gttggctagt 6240 gatgatttgt atgtaagtcg gtacttaagc gggtgcatta cttttggtaa accggttgtc 6300 tggcttggcc atgaggaagc atcgctgaaa tctctcacat attttaatag acctagtgtc 6360 gtttgtgaaa ataaatttaa cgtgttgccc gttgatgtca gtgaacccac ggacaagggg 6420 cctgtgcctg ctgcagtcct tgttaccggc gtccctggag ctgatgcgtc agctggtgcc 6480 ggtattgcca aggagcaaaa agcctgtgct tctgctagtg tggaggatca ggttgttacg 6540 gaggttcgtc aagagccatc tgtttcagct gctgatgtca aagaggttaa attgaatggt 6600 gttaaaaagc ctgttaaggt ggaaggtagt gtggttgtta atgatcccac tagcgaaacc 6660 aaagttgtta aaagtttgtc tattgttgat gtctatgata tgttcctgac agggtgtaag 6720 tatgtggttt ggactgctaa tgagttgtct cgactagtaa attcaccgac tgttagggag 6780 tatgtgaagt ggggtatggg aaagattgta acacccgcta agttgttgtt gttaagagat 6840 gagaagcaag agttcgtagc gccaaaagta gtcaaggcga aagctattgc ctgctattgt 6900 gctgtgaagt ggtttctcct ctattgtttt agttggataa agtttaatac tgacaataag 6960 gttatataca ccacagaagt agcttcaaag cttactttca agttgtgctg tttggccttt 7020 aagaatgcct tacagacgtt taattggagc gttgtgtcta ggggcttttt cctagttgca 7080 acggtctttt tactctggtt taactttttg tatgctaatg ttattttgag tgacttctat 7140 ttgcctaata ttgggcctct ccctacgttt gtgggacaga tagttgcgtg gtttaagact 7200 acatttggtg tgtcaaccat ctgtgatttc taccaggtga cggatttggg ctatagaagt 7260 tcgttttgta atggaagtat ggtatgtgaa ctatgcttct caggttttga tatgctggac 7320 aactatgatg ctataaatgt tgttcaacac gttgtagata ggcgtttgtc ctttgactat 7380 attagcctat ttaaactggt agttgagctt gtaatcggct actctcttta tactgtgtgc 7440 ttctacccac tgtttgtcct tattggaatg cagttattga ccacatggtt gcctgaattc 7500 tttatgctgg agactatgca ttggagtgct cgtttgtttg tgtttgttgc caatatgctt 7560 ccagctttta cgttactgcg attttacatc gtggtgacag ctatgtataa ggtctattgt 7620 ctttgtagac atgttatgta tggatgtagt aagcctggtt gcttgttttg ttataagaga 7680 aaccgtagtg tccgtgttaa gtgtagcacc gttgttggtg gttcactacg ctattacgat 7740 gtaatggcta acggcggcac aggtttctgt acaaagcacc agtggaactg tcttaattgc 7800 aattcctgga aaccaggcaa tacattcata actcatgaag cagcggcgga cctctctaag 7860 gagttgaaac gccctgtgaa tccaacagat tctgcttatt actcggtcac agaggttaag 7920 caggttggtt gttccatgcg tttgttctac gagagagatg gacagcgtgt ttatgatgat 7980 gttaatgcta gtttgtttgt ggacatgaat ggtctgctgc attctaaagt taaaggtgtg 8040 cctgaaacgc atgttgtggt tgttgagaat gaagctgata aagctggttt tctcggcgcc 8100 gcagtgtttt atgcacaatc gctctacaga cctatgttga tggtggaaaa gaaattaata 8160 actaccgcca acactggttt gtctgttagt cgaactatgt ttgaccttta tgtagattca 8220 ttgctgaacg tcctcgacgt ggatcgcaag agtctaacaa gttttgtaaa tgctgcgcac 8280 aactctctaa aggagggtgt tcagcttgaa caagttatgg atacctttat tggctgtgcc 8340 cgacgtaagt gtgctataga ttctgatgtt gaaaccaagt ctattaccaa gtccgtcatg 8400 tcggcagtaa atgctggcgt tgattttacg gatgagagtt gtaataactt ggtgcctacc 8460 tatgttaaaa gtgacactat cgttgcagcc gatttgggtg ttcttattca gaataatgct 8520 aagcatgtac aggctaatgt tgctaaagcc gctaatgtgg cttgcatttg gtctgtggat 8580 gcttttaacc agctatctgc tgacttacag cataggctgc gaaaagcatg ttcaaaaact 8640 ggcttgaaga ttaagcttac ttataataag caggaggcaa atgttcctat tttaactaca 8700 ccgttctctc ttaaaggggg cgctgttttt agtagaatgt tacaatggtt gtttgttgct 8760 aatttgattt gtttcattgt gttgtgggcc cttatgccaa catatgcagt gcacaaatcg 8820 gatatgcagt tgcctttata tgccagtttt aaagttatag ataacggtgt gctaagggat 8880 gtgtctgtta ctgacgcatg cttcgcaaac aaatttaatc aattcgacca atggtatgag 8940 tctacttttg gtcttgctta ttaccgcaac tctaaggctt gtcctgttgt ggttgctgta 9000 atagatcaag acattggcca taccttattt aatgttccta ccacagtttt aagatatgga 9060 tttcatgtgt tgcattttat aacccatgca tttgctactg atagcgtgca gtgttacacg 9120 ccacatatgc aaatccccta tgataatttc tatgctagtg gttgcgtgtt gtcatccctc 9180 tgtactatgc ttgcgcatgc agatggaacc ccgcatcctt attgttatac agggggtgtt 9240 atgcataatg cctctctgta tagttctttg gctcctcatg tccgttataa cctggctagt 9300 tcaaatggtt atatacgttt tcccgaagtg gttagtgaag gcattgtgcg tgttgtgcgc 9360 actcgctcta tgacctactg cagggttggt ttatgtgagg aggccgagga gggtatctgc 9420 tttaatttta atcgttcatg ggtattgaac aacccgtatt atagggccat gcctggaact 9480 ttttgtggta ggaatgcttt tgatttaata catcaagttt taggaggatt agtgcggcct 9540 attgatttct ttgccttaac ggcgagttca gtggctggtg ctatccttgc aattattgtc 9600 gttttggctt tctattattt aatcaagctt aagcgtgcct ttggtgacta cactagtgtt 9660 gtggttatca atgtaattgt gtggtgtata aattttctga tgctttttgt gtttcaggtt 9720 tatcccacat tgtcttgttt atatgcttgt ttctacttct acaccacgct ttatttccct 9780 tcggagataa gtgttgttat gcatttgcaa tggcttgtca tgtatggtgc tattatgccc 9840 ttgtggtttt gcattattta cgtggcagtc gttgtttcaa accatgcatt gtggttgttc 9900 tcttactgcc gcaaaattgg taccgaggtt cgtagtgacg gcacatttga ggaaatggcc 9960 cttactacct ttatgattac taaagaatct tattgtaagt tgaaaaactc tgtttctgat 10020 gttgctttta acaggtactt gagtctttac aacaagtacc gttacttcag tggcaaaatg 10080 gatactgccg cttatagaga ggctgcctgt tcacaactgg caaaggcaat ggaaacattt 10140 aaccataata atggtaatga tgttctctat cagcctccaa ccgcctctgt tactacatca 10200 tttttacagt ctggtatagt gaagatggtg tcgcccacct ctaaagtgga gccttgtatt 10260 gttagtgtta cttatggtaa catgacactt aatgggttgt ggttggatga taaagtttat 10320 tgcccaagac atgttatctg ttcttcagct gacatgacag accctgatta tcctaatttg 10380 ctttgtagag tgacatcaag tgatttttgt gttatgtctg gtcgtatgag ccttactgta 10440 atgtcttatc aaatgcaggg ctgccaactt gttttgactg ttacactgca aaatcctaac 10500 acgcctaagt attccttcgg tgttgttaag cctggtgaga catttactgt actggctgca 10560 tacaatggca gacctcaagg agccttccat gttacgcttc gtagtagcca taccataaag 10620 ggctcctttc tatgtggatc ctgcggttct gtaggatatg ttttaactgg cgatagtgta 10680 cgatttgttt atatgcatca gctagagttg agtactggtt gtcataccgg tactgacttt 10740 agtgggaact tttatggtcc ctatagagat gcgcaagttg tacaattgcc tgttcaggat 10800 tatacgcaga ctgttaatgt tgtagcttgg ctttatgctg ctatttttaa cagatgcaac 10860 tggtttgtgc aaagtgatag ttgttccctg gaggagttta atgtttgggc tatgaccaat 10920 ggttttagct caatcaaagc cgatcttgtc ttggatgcgc ttgcttctat gacaggcgtt 10980 acagttgaac aggtgttggc cgctattaag aggctgcatt ctggattcca gggcaaacaa 11040 attttaggta gttgtgtgct tgaagatgag ctgacaccaa gtgatgttta tcaacaacta 11100 gctggtgtca agctacagtc aaagcgcaca agagttataa aaggtacatg ttgctggata 11160 ttggcttcaa cgtttttgtt ctgtagcatt atctcagcat ttgtaaaatg gactatgttt 11220 atgtatgtta ctacccatat gttgggagtg acattgtgtg cactttgttt tgtaagcttt 11280 gctatgttgt tgatcaagca taagcatttg tatttaacta tgtacatcat gcctgtgtta 11340 tgcacactgt tttacaccaa ctatttggtt gtgtacaaac agagttttag aggtctagct 11400 tatgcttggc tttcacactt tgtccctgct gtagattata catatatgga tgaagtttta 11460 tatggtgttg tgttgctagt agctatggtg tttgttacca tgcgtagcat aaaccacgac 11520 gtcttttcta ttatgttctt ggttggtaga cttgtcagcc tggtatccat gtggtatttt 11580 ggagccaatt tagaggaaga ggtactattg ttcctcacat ccctatttgg cacgtacaca 11640 tggactacta tgttgtcatt ggctaccgct aaggttattg ctaaatggtt ggctgtgaat 11700 gtcttgtact tcacagacgt accgcaaatt aaattagttc tgttgagcta cttgtgtatt 11760 ggttatgtgt gttgttgtta ttggggaatc ttgtcactcc ttaatagcat ttttaggatg 11820 ccattgggcg tctacaatta taaaatctcc gttcaggagt tacgttatat gaatgctaat 11880 ggcttgcgcc cacctagaaa tagttttgag gccctgatgc ttaattttaa gctgttggga 11940 attggtggtg tgccagtcat tgaagtatct caaattcaat caagattgac ggatgttaaa 12000 tgtgctaatg ttgtgttgct taattgcctc cagcacttgc atattgcatc taattctaag 12060 ttgtggcagt attgtagtac tttgcacaat gaaatactgg ctacatctga tttgagcgtg 12120 gccttcgata agttggctca actcttagtt gttttatttg ctaatccagc agcagtggat 12180 agcaagtgcc ttgcaagtat tgaagaagtg agcgatgatt acgttcgcga caatactgtc 12240 ttgcaagcct tacagagtga atttgttaat atggctagct tcgttgagta tgaacttgct 12300 aagaagaatc tagatgaggc taaggctagc ggctctgcca atcaacagca gattaagcag 12360 ctagagaagg cgtgtaatat tgctaagtca gcatatgagc gcgacagagc tgttgctcgt 12420 aagctggaac gtatggctga tttagctctt acaaacatgt ataaagaagc tagaattaat 12480 gataagaaga gtaaggtagt gtctgcattg caaaccatgc tctttagtat ggtgcgtaag 12540 ctagataacc aagctcttaa ttctatttta gacaacgcag ttaagggttg tgtacctttg 12600 aatgcaatac catcattgac ttcgaacact ctgactataa tagtgccaga taagcaggtt 12660 tttgatcagg ttgtggataa tgtgtatgtc acctatgctg ggaatgtatg gcatatacag 12720 tttattcaag atgctgatgg tgctgttaaa caattgaatg agatagatgt taattcaacc 12780 tggcctctag tcattgctgc aaataggcat aatgaagtgt ctactgttgt tttgcagaac 12840 aatgagttga tgcctcagaa gttgagaact caggttgtca atagtggctc agatatgaat 12900 tgtaatactc ctacccagtg ttactataat actactggca cgggtaagat tgtgtatgct 12960 atacttagtg actgtgacgg cctgaagtac actaagatag taaaagaaga tggaaattgt 13020 gttgttttgg aattggatcc tccctgtaag ttttctgttc aggatgtgaa gggccttaaa 13080 attaagtacc tttactttgt gaaggggtgt aatacactgg ctagaggctg ggttgtaggc 13140 accttatcct cgacagtgag attgcaggcg ggtacggcaa ctgagtatgc ctccaactct 13200 gcaatactgt cgctgtgtgc gttttctgta gatcctaaga aaacgtactt ggattatata 13260 aaacagggtg gagttcccgt tactaattgt gttaagatgt tatgtgacca tgctggcact 13320 ggtatggcca ttactattaa gccggaggca accactaatc aggattctta tggtggtgct 13380 tccgtttgta tatattgccg ctcgcgtgtt gaacatccag atgttgatgg attgtgcaaa 13440 ttacgcggca agtttgtcca agtgccctta ggcataaaag atcctgtgtc atatgtgttg 13500 acgcatgatg tttgtcaggt ttgtggcttt tggcgagatg gtagctgttc ctgtgtaggc 13560 acaggctccc agtttcagtc aaaagacacg aactttttaa acggattcgg ggtacaagtg 13620 taaatgcccg tcttgtaccc tgtgccagtg gcttggacac tgatgttcaa ttaagggcat 13680 ttgacatttg taatgctaat cgagctggca ttggtttgta ttataaagtg aattgctgcc 13740 gcttccagcg tgtagatgag gacggcaaca agttggataa gttctttgtt gttaaaagaa 13800 ctaatttaga agtgtataac aaggagaaag aatgctatga gttgacaaaa gaatgcggtg 13860 ttgtggctga acacgagttc ttcacatttg atgtggaggg aagtcgggta ccacacatag 13920 tccgtaaaga tctttcaaag tttactatgt tagatctttg ctatgcattg cgtcattttg 13980 accgcaatga ttgttcaact cttaaggaaa ttctccttac atatgctgag tgtgaagagt 14040 cctacttcca aaagaaggac tggtatgatt ttgttgagaa tcctgatata attaatgtgt 14100 acaagaagct tggtcctata tttaatagag ccctgcttaa cactgccaag tttgcagacg 14160 cattagtgga ggcaggctta gtaggtgttt taacacttga taatcaagat ttatatggtc 14220 aatggtatga ctttggagat tttgtcaaga cagtacctgg ttgtggtgtt gccgtggcag 14280 actcttatta ttcatatatg atgccaatgc tgactatgtg tcatgcgttg gatagtgagt 14340 tgtttgttaa tggtacttat agggagtttg accttgttca gtatgatttt actgatttca 14400 agctagagct gttcactaag tattttaagc attggagtat gacctaccac ccgaacacct 14460 gtgagtgcga ggatgacagg tgcattattc attgcgccaa ttttaatata cttttcagca 14520 tggtcttacc taagacctgt tttgggcctc ttgttaggca gatatttgtg gatggtgttc 14580 ctttcgttgt gtcgatcggt taccattata aagaattagg tgttgttatg aatatggatg 14640 tggatacaca tcgttatcgc ttgtctctta aggacttgct tttgtatgct gcagaccctg 14700 cccttcatgt ggcgtctgct agtgcactgc ttgatttgcg cacatgttgt tttagcgttg 14760 cagctattac aagtggcgta aaatttcaaa cagttaaacc tggaaatttt aatcaggatt 14820 tctacgagtt tattttgagt aaaggcctgc ttaaagaggg gagctccgtt gatttgaagc 14880 acttcttctt tacgcaggat ggtaatgctg ctattactga ttacaattac tacaagtata 14940 atctacccac catggtggat attaagcagt tgttgtttgt tttagaagtt gttaataagt 15000 acttcgagat ctatgagggt gggtgtatac ccgcaacaca ggtcattgtt aataattatg 15060 acaagagtgc tggctatcca tttaataaat ttggaaaggc caggctctat tatgaggcat 15120 tatcatttga ggagcaggat gaaatttatg cgtataccaa acgcaatgtc ctgccgaccc 15180 taactcaaat gaatcttaaa tatgctatta gtgctaagaa tagggcccgc accgttgctg 15240 gtgtctctat tctcagtact atgactggca gaatgtttca tcaaaagtgt ctaaagagta 15300 tagcagctac tcgcggtgtt cctgtagtta taggcaccac gaagttctat ggcggttggg 15360 atgatatgtt acgccgcctt attaaagatg ttgatagtcc tgtactcatg ggttgggact 15420 atcctaaatg tgatcgtgct atgccaaaca tactgcgtat tgttagtagt ttggtgctag 15480 cccgtaaaca tgattcgtgc tgttcgcata cggatagatt ctatcgtctt gcgaacgagt 15540 gcgcccaagt tttgagtgaa attgttatgt gtggtggttg ttattatgtt aaaccaggtg 15600 gcactagtag tggggatgca accactgctt ttgctaattc tgtgtttaac atttgtcaag 15660 ctgtttccgc caatgtatgc tcgcttatgg catgcaatgg acacaaaatt gaagatttga 15720 gtatacgcga gttacaaaag cgcctatact ctaatgtcta tcgtgcggac catgttgacc 15780 ccgcatttgt tagtgagtat tatgagtttt taaacaagca ttttagtatg atgattttga 15840 gtgatgatgg tgttgtgtgt tataattcag agtttgcgtc caagggttat attgctaata 15900 taagtgcctt tcaacaggta ttatattatc aaaacaacgt gtttatgtct gaggccaaat 15960 gttgggtaga aacagacatc gaaaagggac cgcatgaatt ttgttctcaa catacaatgc 16020 tagtcaagat ggatggtgat gaagtctacc ttccataccc tgatccttcg agaatcttag 16080 gagcaggctg ttttgttgat gatttactca agactgatag cgttctcttg atagagcgtt 16140 tcgtaagtct tgcaattgat gcttatcctt tagtatacca tgagaaccca gagtatcaaa 16200 atgtgttccg ggtatattta gaatacatca agaagctgta caatgatctc ggtaatcaga 16260 tcctggacag ctacagtgtt attttaagta cttgtgatgg tcaaaagttt actgacgaga 16320 cgttttacaa gaacatgtat ttaagaagtg cagtgctgca aagcgttggt gcctgcgttg 16380 tctgtagttc tcaaacatca ttacgttgtg gcagttgcat acgcaagcct ttgctgtgtt 16440 gcaaatgcgc ctatgatcat gttatgtcca ctgatcataa atatgtcctg agtgtgtcac 16500 catatgtgtg taattcaccg ggatgtgatg taaatgatgt taccaaattg tatttaggtg 16560 gtatgtcata ttattgtgag gaccataaac cacagtattc attcaaattg gtgatgaatg 16620 gtatggtttt tggtttatat aagcagtctt gtactggttc gccctacata gaggatttta 16680 ataaaatcgc tagttgcaaa tggacagaag tcgatgatta tgtgctagct aatgaatgca 16740 ccgaacgcct taaattgttt gccgcagaaa cgcagaaggc cacagaagag gcctttaagc 16800 aatgttatgc gtcagcaacg atccgtgaga tcgtgagcga tcgggagtta attttatctt 16860 gggaaattgg taaagtccgc ccgccactta ataaaaatta cgtgttcacc ggctaccatt 16920 ttactaataa tggtaagaca gttttaggtg agtatgtttt tgataagagt gagttgacta 16980 atggtgtgta ttatcgcgcc acaaccactt ataagttatc tgtaggtgat gtgttcattt 17040 taacatcaca cgcagtgtct agtttaagtg ctcctacatt agtaccgcag gagaattata 17100 ctagcattcg ttttgctagt gtttatagtg tgcctgagac gtttcagaat aatgtgccta 17160 attatcagca cattggaatg aagcgctatt gtactgtaca gggaccgcct ggtactggta 17220 agtcccatct agccattggg ctagctgttt attattgtac agcgcgcgtg gtgtataccg 17280 ctgctagcca tgctgcagtt gacgcgctgt gtgaaaaggc acataaattt ctcaacatca 17340 acgactgcac gcgtattgtt cctgcaaagg tgcgtgtaga ttgttatgat aaattcaagg 17400 tcaatgacac cactcgcaag tatgtgttta ctacaataaa tgcattacct gagttggtga 17460 ctgacattat tgtcgttgat gaagttagta tgcttaccaa ctatgagctg tctgttatta 17520 acagtcgtgt tagggctaag cattatgtgt atattggcga cccggcgcag ttacctgcac 17580 cacgtgtgct actgaataag ggaactctag aacctagata ttttaattcc gttaccaagc 17640 taatgtgttg tttgggtcca gatattttct tgggcacctg ttatagatgc cctaaggaga 17700 ttgtggatac ggtgtcagcc ttggtttata ataataagct gaaggctaaa aatgataata 17760 gctccatgtg ctttaaggtt tattataagg gccagactac acatgagagt tctagtgctg 17820 ttaatatgca gcaaatacat ttaatttcca agtttctgaa ggcaaacccc agttggagta 17880 acgccgtatt tattagtcct tataactcgc agaactatgt tgctaagaga gtcttgggat 17940 tacaaaccca gacagtagac tcagcgcagg gttctgaata tgattttgtt atctactcac 18000 agactgcgga aacagcgcat tctgtcaatg taaatagatt caatgttgct attacacgtg 18060 ctaagaaggg tattctctgt gtcatgagta gtatgcaatt atttgagtct cttaatttta 18120 ctacactgac gttggataag attaacaatc cacgattaca gtgtactaca aatttgttta 18180 aggattgtag caggagctat gtaggatatc acccagccca tgcaccatcc tttttggcag 18240 ttgatgacaa atataaggta ggcggtgatt tagccgtttg ccttaatgtt gctgattctg 18300 ctgtcactta ttcgcggctt atatcactca tgggattcaa gcttgacttg acccttgatg 18360 gttattgtaa gctgtttata actagagatg aagctatcaa acgtgttaga gcctgggttg 18420 gcttcgatgc agaaggtgcc catgcgatac gtgatagcat tgggacaaat ttcccattac 18480 aattaggctt ttcgactgga attgattttg ttgtcgaagc cactggaatg tttgctgaga 18540 gagatggtta tgtctttaaa aaggcagccg cacgagctcc tcctggcgaa caatttaaac 18600 accttatccc acttatgtca agagggcaga aatgggatgt ggttcgcatt agaatagtac 18660 aaatgttgtc agaccaccta gtggatttgg cagacagtgt tgtacttgtg acgtgggctg 18720 ccagctttga gctcacatgt ttgcgatatt tcgctaaagt tggaagagaa gttgtgtgta 18780 gtgtctgcac caagcgtgcg acatgtttta attctagaac tggatactat ggatgctggc 18840 gacatagtta ttcctgtgat tacctgtaca acccactaat agttgacatt caacagtggg 18900 gatatacagg atctttaact agcaatcatg atcctatttg cagcgtgcat aagggtgctc 18960 atgttgcatc atctgatgct atcatgaccc ggtgtctagc tgttcatgat tgcttttgta 19020 agtctgttaa ttggaattta gaatacccca ttatttcaaa tgaggtcagt gttaatacct 19080 cctgcaggtt attgcagcgc gtaatgttta gggctgcgat gctatgcaat aggtatgatg 19140 tgtgttatga cattggcaac cctaaaggtc ttgcctgtgt caaaggatat gattttaagt 19200 tctatgacgc ctcccctgtt gttaagtctg ttaaacagtt tgtttacaaa tacgaggcac 19260 ataaagatca atttttagat ggtttgtgta tgttttggaa ctgcaatgtg gataagtatc 19320 cagcgaatgc agttgtgtgt aggtttgaca cgcgtgtgtt gaacaaatta aatctccctg 19380 gctgtaatgg tggcagtttg tatgttaaca aacatgcatt ccacaccagt ccctttaccc 19440 gggctgcctt cgagaatttg aagcctatgc ctttctttta ttattcagat acgccctgtg 19500 tgtatatgga aggcatggaa tctaagcagg tcgattatgt cccattgaga agcgctacat 19560 gcatcacaag atgcaattta ggtggcgctg tttgtttaaa acatgctgag gagtatcgtg 19620 agtaccttga gtcttacaat acggcaacca cagcgggttt tactttttgg gtctataaga 19680 cttttgattt ttacaacctt tggaatactt ttactaggct ccaaagttta gaaaatgtag 19740 tgtataacct ggtcaacgct ggacactttg atggccgggc gggtgaactg ccttgtgctg 19800 ttataggtga gaaagtcatt gccaagattc aaaatgagga tgtcgtggtc tttaaaaata 19860 acacgccatt ccccactaat gtggctgtcg aattatttgc taagcgcagt attcggcccc 19920 accccgagct taagctcttt agaaatttga atattgacgt gtgctggagt cacgtccttt 19980 gggattatgc taaggatagt gtgttttgca gttcgacgta taaggtctgc aaatacacag 20040 atttacagtg cattgaaagc ttgaatgtac tttttgatgg tcgtgataat ggtgctcttg 20100 aagcttttaa gaagtgccgg aatggcgtct acattaacac gacaaaaatt aaaagtctgt 20160 cgatgattaa aggcccacaa cgtgccgatt tgaatggcgt agttgtggag aaagttggag 20220 attctgatgt ggaattttgg tttgctgtgc gtaaagacgg tgacgatgtt atcttcagcc 20280 gtacagggag ccttgaaccg agccattacc ggagcccaca aggtaatccg ggtggtaatc 20340 gcgtgggtga tctcagcggt aatgaagctc tagcgcgtgg cactatcttt actcaaagca 20400 gattattatc ttctttcaca cctcgatcag agatggagaa agattttatg gatttagatg 20460 atgatgtgtt cattgcaaaa tatagtttac aggactacgc gtttgaacac gttgtttatg 20520 gtagttttaa ccagaagatt attggaggtt tgcatttgct tattggctta gcccgtaggc 20580 agcaaaaatc caatctggta attcaagagt tcgtgacata cgactctagc attcattcgt 20640 actttatcac tgacgagaac agtggtagta gtaagagtgt gtgcactgtt attgatttat 20700 tgttagatga ttttgtggac attgtaaagt ccctgaatct aaagtgtgtg agtaaggttg 20760 ttaatgttaa tgtggatttt aaggacttcc agtttatgtt gtggtgcaat gaggagaagg 20820 tcatgacttt ctatcctcgt ttgcaggctg ctgctgactg gaaacctggt tatgttatgc 20880 ctgtcttata taagtatttg gaatcgcctc tggaaagagt aaacctctgg aattatggca 20940 agccgattac tttacctaca ggatgtatga tgaatgttgc taagtatact caattatgtc 21000 aatatttgag cactacaaca ttagcagttc cggctaatat gcgtgtctta caccttggtg 21060 ccggttcgga taagggtgtt gcccctgggt ctgcagttct taggcagtgg ctaccagcgg 21120 gaagtattct tgtagataat gatgtgaatc catttgtgag tgacagtgtc gcctcatatt 21180 atggaaattg tataacctta ccctttgatt gtcagtggga tctgataatt tctgatatgt 21240 acgaccctct tactaagaac attggggagt acaacgtgag taaagatgga ttctttactt 21300 acctctgtca tttaattcgt gacaagttgg ctctgggtgg cagtgttgcc ataaaaataa 21360 cagagttttc ttggaacgct gagttatata gtttaatggg gaagtttgcg ttctggacaa 21420 tcttttgcac caacgtaaac gcctcttcaa gtgaaggatt tttgattggc ataaattggt 21480 tgaataagac ccgtaccgaa attgacggta aaaccatgca tgccaattat ctgttttgga 21540 gaaatagtac aatgtggaat ggaggggctt acagtctctt tgacatgagt aagttccctt 21600 tgaaagcggc tggtacggct gttgttagcc ttaaaccaga ccaaataaat gacttagtcc 21660 tctccttgat tgagaagggc aagttattag tgcgtgatac acgcaaagaa gtttttgttg 21720 gcgatagcct agtaaatgtc aaataa 21746 <210> 16 <211> 9589 <212> DNA <213> Artificial Sequence <220> <223> COVAX_SYNCoat56 <400> 16 atctatactt gtcgtggctg tgaaaatggc ctttgctgac aagcctaatc atttcataaa 60 ctttcccctg gcccaattta gtggctttat gggtaagtat ttaaagctac agtctcaact 120 tgtggaaatg ggtttagact gtaaattaca gaaggcacca catgttagta ttaccctgct 180 tgatattaaa gcagaccaat acaaacaggt ggaatttgca atacaagaaa taatagatga 240 tctggcggca tatgagggag atattgtctt tgacaaccct cacatgcttg gcagatgcct 300 tgttcttgat gttagaggat ttgaagagtt gcatgaagat attgttgaaa ttctccgcag 360 aaggggttgc acggcagatc aatccagaca ctggattccg cactgcactg tggcccaatt 420 tgacgaagaa agagaaacaa aaggaatgca attctatcat aaagaaccct tctacctcaa 480 gcataacaac ctattaacgg atgctgggct tgagctcgtg aagataggtt cttccaaaat 540 agatgggttt tattgtagtg aactgagtgt ttggtgtggt gagaggcttt gttataagcc 600 tccaacaccc aaattcagtg atatatttgg ctattgctgc atagataaaa tacgtggtga 660 tttagaaata ggcgacctgc cgcaggatga tgaggaagcg tgggccgagc taagttacca 720 ctatcaaaga aacacctact tcttcagaca tgtgcacgat aatagcatct attttcgtac 780 cgtgtgtaga atgaagggtt gtatgtgttg atttgttttt acactattag tgtaataagc 840 ttattatttt gttgaaaagg gcaggatgtg catagctatg gctcctcgca cactgctttt 900 gctgatttga tgtcagctgg tgtttgggtt caatgaacct cttaacatcg tttcacattt 960 aaatgatgac tggtttctat ttggtgacag tcggtccgac tgtacctatg tagaaaataa 1020 cggtcatcct aaattagatt ggcttgacct cgacccaaag ttgtgtaatt caggaaagat 1080 ttccgcaaag agtggtaact ctctctttag gagttttcac ttcactgatt tttacaatta 1140 tacgggtgag ggataccaaa ttgtatttta tgaaggagtt aattttagtc ccagccatgg 1200 ctttaaatgc ctggctcatg gagataataa aagatggatg ggcaataaag ctcgatttta 1260 tgcccgagtg tatgagaaga tggcccaata taggagccta tcgtttgtta atgtgtctta 1320 tgcctatgga ggtaatgcaa agcccgcctc catttgcaaa gacaatactt taacactcaa 1380 taaccccacc ttcatatcga aggagtctaa ttatgttgat tactactacg agagtgaggc 1440 taatttcaca ctagaaggtt gtgatgaatt tatagtaccg ctctgtggtt ttaatggcca 1500 ttccaagggc tcgtcgtcgg atgctgccaa taaatattat actgactctc agagttacta 1560 taatatggat attggtgtct tatatgggtt caattcgacc ttggatgttg gcaacactgc 1620 taaggatccg ggtcttgatc tcacttgtag gtatcttgca ttgactcctg gtaattataa 1680 ggctgtgtcc ttagaatatt tgttaagctt accctcaaag gctatttgcc tccataagac 1740 aaagcgcttt atgcctgtgc aggtagttga ctcaaggtgg agtagcatcc gccagtcaga 1800 caatatgacc gctgcagcct gtcagctgcc atattgtttc tttcgcaaca catctgcgaa 1860 ttatagtggt ggcacacatg atgcgcacca tggtgatttt catttcaggc agttattgtc 1920 tggtttgtta tataatgttt cctgtattgc ccagcagggt gcatttcttt ataataatgt 1980 gtcgtcctct tggccagcct atgggtacgg tcattgtcca acggcagcta acattggtta 2040 tatggcacct gtttgtatct atgaccctct cccggtcata ctgctaggtg tgttattggg 2100 tatagctgtg ttgactattg tgtttctgat gttttatttt atgacggata gcggtgttag 2160 attgcatgag gcataatcta aacatgctgt tcgtgtttat tctatttttg ccctcttgtt 2220 tagggtatat tggtgatttt agatgtatcc agcttgtgaa ttcaaacggt gctaatgtta 2280 gtgctccaag cattagcacc gagacggttg aagtttcaca aggcctgggg acatattatg 2340 tgttagatcg agtttattta aatgccacat tattgcttac tggttactac ccggtcgatg 2400 gttctaagtt tagaaacctc gctcttacgg gaactaactc agttagcttg tcgtggtttc 2460 aaccacccta tttaagtcag tttaatgatg gcatatttgc gaaggtgcag aaccttaaga 2520 caagtacgcc atcaggtgca actgcatatt ttcctactat agttataggt agtttgtttg 2580 gctatacttc ctataccgtt gtaatagagc catataatgg tgttataatg gcctcagtgt 2640 gccagtatac catttgtcag ttaccttaca ctgattgtaa gcctaacact aatggtaata 2700 aactgatagg gttttggcac acggatgtaa aacccccaat ttgtgtgtta aagcgaaatt 2760 tcacgcttaa tgttaatgct gatgcatttt attttcattt ctaccaacat ggtggtactt 2820 tttatgcgta ctatgcggat aaaccctccg ctactacgtt tttgtttagt gtatatatcg 2880 gcgatatttt aacacagtat tatgtgttac ctttcatctg caacccaaca gctggtagca 2940 cttttgctcc gcgctattgg gttacacctt tggttaagcg ccaatatttg tttaatttca 3000 accagaaggg tgtcattact agtgctgttg attgtgctag tagttatacc agtgaaataa 3060 aatgtaagac ccagagcatg ttacctagca ctggtgtcta tgagttatcc ggttatacgg 3120 tccaaccagt tggagttgta taccggcgtg ttgctaacct cccagcttgt aatatagagg 3180 agtggcttac tgctaggtca gtcccctccc ctctcaactg ggagcgtaag acttttcaga 3240 attgcaattt taacttaagc agcctgttac gttatgttca ggctgagagt ttgttttgta 3300 ataatatcga tgcttccaaa gtgtatggcc gctgctttgg tagtatttca gttgataagt 3360 ttgctgtacc ccgaagtagg caagttgatt tacagcttgg taactctgga tttctgcaga 3420 ctgctaatta taagattgat acagctgcca cttcgtgtca gctgcattac accttgccta 3480 agaataatgt caccataaac aaccataacc cctcgtcttg gaataggagg tatggcttta 3540 atgatgctgg cgtctttggc aaaaaccaac atgacgttgt ttacgctcag caatgtttta 3600 ctgtaagatc tagttattgc ccgtgtgctc aaccggacat agttagccct tgcactactc 3660 agactaagcc taagtctgct tttgttaatg tgggtgacca ttgtgaaggc ttaggtgttt 3720 tagaagataa ttgtggcaat gctgatccac ataagggttg tatctgtgcc aacaattcat 3780 ttattggatg gtcacatgat acctgccttg ttaatgatcg ctgccaaatt tttgctaata 3840 tattgctgaa tggcattaat agtggtacca catgttccac agatttgcag ttgcctaata 3900 ctgaagtggt tactggcatt tgtgtcaaat atgacctcta cggtattact ggacaaggtg 3960 tttttaaaga ggttaaggct gactattata atagctggca aacccttctg tatgatgtta 4020 atggtaattt gaatggtttt cgtgatctta ccactaacaa gacttatacg ataaggagct 4080 gttatagtgg ccgtgtttct gctgcatttc ataaagatgc acccgaaccg gctctgctct 4140 atcgtaatat aaattgtagc tatgttttta gcaataatat ctcccgtgag gagaacccac 4200 ttaattactt tgatagttat ctgggttgtg ttgttaatgc tgataaccgc acggatgagg 4260 cgcttcctaa ttgtgatctc cgtatgggtg ctggcttatg cgttgattat tcaaaatcac 4320 gcagggctca ccgatcagtt tctactggct atcggttaac tacatttgag ccatacactc 4380 cgatgttagt taatgatagt gtccaatccg ttgatggatt atatgagatg caaataccaa 4440 ccaattttac tattgggcac catgaggagt tcattcaaac tagatctcca aaggtgacta 4500 tagattgtgc tgcatttgtc tgtggtgata acactgcatg caggcagcag ttggttgagt 4560 atggctcttt ctgtgttaat gttaatgcca ttcttaatga ggttaataac ctcttggata 4620 atatgcaact acaagttgct agtgcattaa tgcagggtgt tactataagc tcgagactgc 4680 cagacggcat ctcaggccct atagatgaca ttaattttag tcctctactt ggatgcatag 4740 gttcaacatg tgccgaggac ggcaatggac ctagtgcaat ccgagggcgt tctgctatag 4800 aggatttgtt atttgacaag gtcaaattat ctgatgttgg ctttgtcgag gcttataata 4860 attgcaccgg tggtcaagaa gttcgtgacc tcctttgtgt acaatctttt aatggcatca 4920 aagtattacc tcctgtgttg tcagagagtc agatctctgg ctacacaacc ggtgctactg 4980 cggcagctat gttcccaccg tggtcagcag ctgccggtgt gccatttagt ttaagtgttc 5040 aatatagaat taatggttta ggtgtcacta tgaatgtgct tagtgagaac caaaagatga 5100 ttgctagtgc ttttaacaat gcgctgggtg ctatccagga tgggtttgat gcaaccaatt 5160 ctgctttagg taagatccag tccgttgtta atgcaaatgc tgaagcactc aataacttac 5220 taaatcaact ttctaacagg tttggtgcta ttagtgcttc tttacaagaa attctaactc 5280 ggcttgaggc tgtagaagca aaagcccaga tagatcgtct tattaatggc aggttaactg 5340 cacttaatgc gtatatatcc aagcaactta gtgatagtac gcttattaaa gttagtgctg 5400 ctcaggccat agaaaaggtc aatgagtgcg ttaagagcca aaccacgcgt attaatttct 5460 gtggcaatgg taatcatata ttatctcttg tccagaatgc gccttatggc ttatatttta 5520 tacacttcag ctatgtgcca atatccttta caaccgcaaa tgtgagtcct ggactttgca 5580 tttctggtga tagaggatta gcacctaaag ctggatattt tgttcaagat gatggagaat 5640 ggaagttcac aggcagttca tattactacc ctgaacccat tacagataaa aacagtgtca 5700 ttatgagtag ttgcgcagta aactacacaa aggcacctga agttttcttg aacacttcaa 5760 tacctaatcc acccgacttt aaggaggagt tagataaatg gtttaagaat cagacgtcta 5820 ttgcgcctga tttatctctc gatttcgaga agttaaatgt tactttgctg gacctgacgt 5880 atgagatgaa caggattcag gatgcaatta agaagttaaa tgagagctac atcaacctca 5940 aggaagttgg cacatatgaa atgtatgtga aatggccttg gtatgtttgg ttgctaattg 6000 gattagctgg tgtagctgtt tgtgtgttgt tattctttat atgttgctgc acaggttgtg 6060 gctcatgttg ttttaagaag tgtggaaatt gttgtgatga gtatggagga caccaggaca 6120 gtattgtgat acataatatt tcctctcatg aggattgact atcacagcct ctcctggaaa 6180 gacagaaaat ctaaacaatt tatagcattc tcattgctac ctggccccgt aagaggcagt 6240 catagctatg gccgtgttgg tcctaaggct acattggctg ctgtctttat tggtccattt 6300 attgtagcat gtatgctagg cattggccta gtttatttat tgcaattgca agttcaaatt 6360 tttcatgtta aggataccat acgtgtgact ggcaagccag ccactgtgtc ttatactaca 6420 agtacaccag taacaccgag cgcgacgacg ctcgatggta ctacgtatac tttaattaga 6480 cccactagct cttatacaag agtttatctt ggtactccaa gaggttttga ttatagtaca 6540 tttgggccta agaccctaga ttatgttact aatctaaacc tcatcttaat tctggtcgtc 6600 catatacttt taaggcattg tccaggcata tgaggccaac agccacatgg atttggcatg 6660 tgagtgatgc atggttacgc cgcacgcggg actttggtgt cattcgccta gaagattttt 6720 gttttcaatt taattatagc caaccccgag ttggttattg tagagttcct ttaaaggctt 6780 ggtgtagcaa ccagggtaaa tttgcagcgc agtttaccct aaaaagttgc gaaaaaccag 6840 gtcacgaaaa atttattact agcttcacgg cctacggcag aactgtccaa caggccgtta 6900 gcaagttagt agaagaagct gttgatttta ttctttttag ggccacgcag ctcgaaagaa 6960 atgtttaatt tattccttac agacacagta tggtatgtgg ggcagattat ttttatattc 7020 gcagtgtgtt tgatggtcac cataattgtg gttgccttcc ttgcgtctat caaactttgt 7080 attcaacttt gcggtttatg taatactttg gtgctgtccc cttctattta tttgtatgat 7140 aggagtaagc agctttataa gtactataat gaagaaatga gactgcccct attagaggtg 7200 gatgatatct aatccaaaca ttatgagtag tactactcag gccccagagc ccgtctatca 7260 atggaccgcc gacgaggcag ttcaattcct taaggaatgg aacttctcgt tgggcattat 7320 actactcttt attactatca tactacagtt cggttacacg agccgtagca tgtttattta 7380 tgttgtgaaa atgataatct tgtggttaat gtggccactg actattgttt tgtgtatttt 7440 caattgcgtg tatgcgctaa ataatgtgta tcttggattt tctatagtgt ttactatagt 7500 gtccattgta atctggatca tgtattttgt gaacagcata aggttgttta tcaggactgg 7560 tagctggtgg agcttcaacc ccgaaacaaa caaccttatg tgtatagata tgaaaggtac 7620 cgtgtatgtt agacccatta ttgaggatta ccatacacta acagccacta ttattcgtgg 7680 ccacctctac atgcaaggtg ttaagctagg caccggtttc tctttgtctg acttgcccgc 7740 ttatgttaca gttgctaagg tgtcacacct ttgcacttat aagcgcgcat tcttagacaa 7800 ggtagacggt gttagcggtt ttgctgttta tgtgaagtcc aaggtcggaa attaccgact 7860 gccctcaaac aaaccgagtg gcgcggacac cgcattgttg agaacctaat ctaaacttta 7920 aggatgtctt ttgttcctgg gcaagaaaat gccggtggca gaagctcctc tgtaaaccgc 7980 gctggtaatg gaatcctcaa gaaaaccact tgggctgacc aaaccgagcg tggaccaaat 8040 aatcaaaata gaggcagaag gaatcagcca aagcagactg caactactca acccaactcc 8100 gggagtgtgg ttccccatta ctcctggttt tctggcatta cccagttcca aaagggaaag 8160 gagtttcagt ttgcagaagg acaaggagtg cctattgcca atggaatccc cgcttcagag 8220 caaaagggat attggtatag acacaaccgc cgttctttta aaacacctga tgggcagcag 8280 aagcaattac tgcccagatg gtatttttac tatcttggca cagggcccca tgctggagcc 8340 agttatggag acagcattga aggcgtcttt tgggttgcaa acagccaagc ggacaccaat 8400 acccgctctg atattgtcga aagggaccca agcagtcatg aggctattcc tactaggttt 8460 gcgcccggca cggtattgcc tcagggcttt tatgttgaag gctctggaag gtctgccccg 8520 gccagccgat ctggttcgcg gtcacaatcc cgtgggccaa ataatcgcgc tagaagcagt 8580 tccaaccagc gccagcctgc ctctactgta aaacctgata tggccgaaga aattgctgct 8640 cttgttttgg ctaagctcgg taaagatgcc ggccagccca agcaagtaac gaagcaaagt 8700 gccaaagaag tcaggcagaa aattttaaac aagcctcgcc aaaagaggac tccaaacaag 8760 cagtgcccag tgcagcagtg ttttggaaag agaggcccca atcagaattt tggaggctct 8820 gaaatgttaa aacttggaac tagtgatcca cagttcccca ttcttgcaga gttggctcca 8880 acagttggtg ccttcttctt tggatctaaa ttagaattgg tcaaaaagaa ttctggtggt 8940 gctgatgaac ccaccaaaga tgtgtatgag ctgcaatatt caggtgcagt tagatttgat 9000 agtactctac ctggttttga gactatcatg aaagtgttga atgagaattt gaatgcctac 9060 cagaaggatg gtggtgcaga tgtggtgagc ccaaagcccc aaagaaaagg gcgtagacag 9120 gctcaggaaa agaaagatga agtagataat gtaagcgttg caaagcccaa aagctctgtg 9180 cagcgaaatg taagtagaga attaacccca gaggatagaa gtctgttggc tcagatcctt 9240 gatgatggcg tagtgccaga tgggttagaa gatgactcta atgtgtaaag agaatgaatc 9300 ctatgtcggc gctcggtggt aacccctcgc gagaaagtcg ggataggaca ctctctatca 9360 gaatggatgt cttgctgtca taacagatag agaaggttgt ggcagaccct gtatcaatta 9420 gttgaaagag attgcaaaat agagaatgtg tgagagaagt tagcaaggtc ctacgtctaa 9480 ccataagaac ggcgataggc gccccctggg aacagctcac atcagggtac tattcctgca 9540 atgccctagt aaatgaatga agttgatcat ggccaattgg aagaatcac 9589 <210> 17 <211> 3822 <212> DNA <213> Artificial Sequence <220> <223> COVAX-S19-1 <400> 17 atgtttgttt ttcttgtttt attgccacta gtctctagtc agtgtgttaa tcttacaacc 60 agaactcaat taccccctgc atacactaat tctttcacac gtggtgttta ttaccctgac 120 aaagttttca gatcctcagt tttacattca actcaggact tgttcttacc tttcttttcc 180 aatgttactt ggttccatgc tatacatgtc tctgggacca atggtactaa gaggtttgat 240 aaccctgtcc taccatttaa tgatggtgtt tactttgctt ccactgagaa gtctaacata 300 ataagaggct ggatttttgg tactacttta gattcgaaaa cccagtccct acttattgtt 360 aataacgcta ctaatgttgt tatcaaagtc tgtgaatttc aattttgtaa cgatccattt 420 ttgggtgttt attaccacaa aaacaacaaa agttggatgg aaagtgagtt cagagtttat 480 tctagtgcga ataattgcac ttttgaatac gtctctcagc cttttcttat ggaccttgaa 540 ggaaaacagg gtaatttcaa aaatcttagg gaatttgtgt tcaagaatat tgatggttac 600 ttcaagatat actctaagca cacgcctatt aatttagtgc gtgatctccc tcagggtttt 660 tcggctttag aaccattggt agatttgcca ataggtatta acatcactag gtttcaaact 720 ttacttgctt tacatagaag ttatttaact cctggtgatt cttcttcagg ttggacagct 780 ggtgctgcag cttattatgt gggttatctt caacctagga cttttctact gaagtacaat 840 gaaaatggaa ccattacaga tgctgtagac tgtgcacttg accctctctc agaaacaaag 900 tgtacgttga aatccttcac tgtagaaaaa ggaatctatc aaacttctaa ctttagagtc 960 caaccaacag aatctattgt tagatttcct aacatcacaa acttgtgccc ttttggtgaa 1020 gtttttaacg ccaccagatt tgcatctgtt tatgcttgga acaggaagag aatcagcaac 1080 tgtgttgctg attattctgt cctgtataat tccgcatcat tttccacttt taagtgttat 1140 ggagtgtctc ctactaaatt aaatgatctc tgctttacta atgtctatgc agattcattt 1200 gtaattagag gtgatgaagt cagacaaatc gctccagggc aaactggaaa gattgctgat 1260 tataactaca aattaccaga tgattttaca ggctgcgtta tagcttggaa ttctaacaat 1320 cttgattcta aggttggtgg taattataat tacctgtaca gattgtttag gaagtctaat 1380 ctcaaacctt ttgagagaga tatttcaact gaaatctatc aggccggtag cacaccttgt 1440 aatggtgttg aaggttttaa ttgttacttt cctctgcaat catatggttt ccaacccact 1500 aatggtgttg gttaccaacc atacagagta gtagtacttt cttttgaact tctacatgca 1560 ccagcaactg tttgtggacc taaaaagtct actaatttgg ttaagaacaa gtgtgtcaat 1620 ttcaacttca atggtttaac aggcacaggt gttcttactg agtctaacaa aaagtttctg 1680 cctttccaac aatttggcag agacattgct gacactactg atgctgttcg tgatccacaa 1740 acacttgaga ttcttgacat tacaccatgt tcttttggtg gtgtcagtgt tataacacca 1800 ggaacaaata cttctaacca ggttgctgtt ctttatcagg atgttaactg cacagaagtc 1860 cctgttgcta ttcatgcaga tcaacttact cctacttggc gtgtttattc tacaggttct 1920 aatgtttttc aaacacgtgc aggctgttta ataggggctg aacatgtcaa caactcatat 1980 gagtgtgaca tacccattgg tgcaggtata tgcgctagtt atcagactca gactaattct 2040 cctcggagag caagaagtgt agctagtcaa tccatcattg cctacactat gtcacttggt 2100 gcagaaaatt cagttgctta ctctaataac tctattgcca tacccacaaa ttttactatt 2160 agcgttacca cagaaattct accagtgtct atgaccaaga catcagtaga ttgtacaatg 2220 tacatttgtg gtgattcaac tgaatgcagc aatcttttgt tgcaatatgg cagtttttgt 2280 acacaattaa accgtgcttt aactggaata gctgttgaac aagacaaaaa cacccaagaa 2340 gtttttgcac aagtcaaaca aatttacaag acaccaccaa ttaaagattt tggcggtttt 2400 aattttagcc agatactgcc agatccatca aaaccaagca agaggtcatt tattgaagat 2460 ctactgttca acaaagtgac acttgcagat gctggcttca tcaaacaata tggtgattgc 2520 cttggtgata ttgctgctag agacctcatt tgtgcacaaa agtttaacgg ccttactgtt 2580 ttgccacctt tgctcacaga tgaaatgatt gctcaataca cttctgcact gttagcaggt 2640 acaatcactt ctggttggac ttttggtgca ggtgctgcat tacaaatacc atttgctatg 2700 caaatggctt ataggtttaa tggtattgga gttacacaga atgttctcta tgagaaccaa 2760 aaattgattg ccaaccaatt taatagtgct attggcaaaa ttcaagactc actttcttcc 2820 acagcaagtg cacttggaaa acttcaagat gtggtcaacc aaaatgcaca agctttaaac 2880 acgcttgtta aacaacttag ctccaatttt ggtgcaattt caagtgtttt aaacgacatc 2940 ctttcacgtc ttgacaaagt tgaggctgaa gtgcaaattg ataggttgat cacaggcaga 3000 cttcaaagtt tgcagacata tgtgactcaa caattaatta gagctgcaga aatcagagct 3060 tctgctaatc ttgctgctac taaaatgtca gagtgtgtac ttggacaatc aaaaagagtt 3120 gacttttgcg gaaagggcta tcatcttatg tcatttcctc agtcagcacc tcatggtgtc 3180 gtctttttgc atgtgactta tgtccctgca caagaaaaga acttcacaac tgctcctgcc 3240 atttgtcatg atggaaaagc acactttcct cgtgaaggtg tctttgtttc aaatggcaca 3300 cactggtttg taacacaaag gaatttttat gaaccacaaa tcattactac agacaacaca 3360 tttgtgtctg gtaactgtga tgttgtaata ggaattgtca acaacacagt ttatgatcct 3420 ttgcaacctg aattagactc attcaaggag gagcttgata aatacttcaa gaaccatacc 3480 tcaccagatg ttgatttagg tgacatctct ggcattaatg cttcagttgt aaacattcag 3540 aaagaaatcg accgcctcaa tgaggttgcc aagaatttaa atgaatctct catcgatctc 3600 caagaacttg gaaagtatga gcagtatata aaatggccat ggtacatttg gctaggtttt 3660 atagctggct tgattgccat agtaatggtg acaattatgc tttgctgtat gaccagttgc 3720 tgtagttgtc tcaagggctg ttgttcttgt ggatcctgct gcaaatttga cgaggacgac 3780 tctgagccag tgctcaaagg agtcaaatta cattacacat aa 3822 <210> 18 <211> 1273 <212> PRT <213> Artificial Sequence <220> <223> S-Protein_Sars-CoV2 <400> 18 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu 1010 1015 1020 Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 1040 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala 1045 1050 1055 Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu 1060 1065 1070 Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His 1075 1080 1085 Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val 1090 1095 1100 Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr 1105 1110 1115 1120 Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1125 1130 1135 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1140 1145 1150 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 1155 1160 1165 Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1170 1175 1180 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu 1185 1190 1195 1200 Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1205 1210 1215 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile 1220 1225 1230 Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val 1250 1255 1260 Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <210> 19 <211> 4486 <212> DNA <213> Artificial Sequence <220> <223> COVAX-S19-2 <400> 19 acgaacttat ggatttgttt atgagaatct tcacaattgg aactgtaact ttgaagcaag 60 gtgaaatcaa ggatgctact ccttcagatt ttgttagagc tactgcaacg ataccgatac 120 aagcatcact tcctttcgga tggcttattg ttggcgttgc acttcttgct gtttttcaga 180 gcgcttccaa aatcataacc ctcaaaaaga gatggcaact agcactctcc aagggtgttc 240 actttgtttg caacttgctg ttgttgtttg taacagttta ctcacatctt ttgcttgttg 300 ctgctggcct tgaagcccct tttctctatc tttatgcttt agtctacttc ttgcagagta 360 taaactttgt acgcataata atgaggcttt ggctttgctg gaaatgccgt tccaaaaacc 420 cattacttta tgatgccaac tattttcttt gctggcatac taattgttac gactattgta 480 taccttacaa tagtgtaact tcttcaattg tcattacttc aggtgatggc acaacaagtc 540 ctatttctga acatgactac cagattggtg gttatactga aaaatgggaa tctggagtaa 600 aagactgtgt tgtattacac agttacttca cttcagacta ttaccagctg tactcaactc 660 aattgagtac agacactggt gttgaacatg ttaccttctt catctacaat aaaatcgttg 720 atgagcctga agaacatgtc caaattcaca caatcgacgg ttcatccgga gttgttaatc 780 cagtaatgga accaatttat gatgaaccga cgacgactac tagcgtgcct ttgtaagcac 840 aagctgatga gtacgaactt atgtactcat tcgtttcgga agagacaggt acgttaatag 900 ttaatagcgt acttcttttt cttgctttcg tggtattctt gctagttaca ctagccattc 960 ttactgcgct tcgattgtgt gcgtactgtt gcaatattgt taacgtgagt cttgtaaaac 1020 cttcttttta cgtttactct cgtgttaaaa atctgaattc ttctcgggtt cctgatcttc 1080 tggtctaaac gaactaaata ttatattagt ttttctgttt ggaactttaa ttttagccat 1140 ggcagattcc aacggtacta ttaccgttga ggagctgaaa aagctccttg aacaatggaa 1200 cctagtaata ggtttcctat tccttacatg gatttgcctg ctgcaatttg cctatgccaa 1260 caggaatagg tttttgtaca tcattaagtt gattttcctc tggctgttat ggccagtaac 1320 tttagcttgt tttgtgcttg ctgctgttta cagaataaat tggatcaccg gtggaattgc 1380 tattgcaatg gcttgtcttg taggattgat gtggctaagc tacttcattg cttctttcag 1440 actgtttgcg cgtacgcgtt ccatgtggtc attcaatcca gaaactaaca ttcttctcaa 1500 cgtgccactc catggaacta ttctgactag accgcttcta gaaagtgaac tcgtaatcgg 1560 agctgttatc cttcgtggac atcttcgtat tgctggacat catctaggac gctgtgacat 1620 caaggatcta cctaaagaaa tcactgttgc tacatcacga acgctttctt attacaaatt 1680 gggagcttca cagcgtgtag caggtgattc aggttttgct gcatatagtc gctacaggat 1740 tggcaactat aaattaaaca cagaccattc cagtagcagt gacaatattg ctttgcttgt 1800 acagtaagtg acaacagatg tttcatctcg ttgactttca ggttactata gcagagatat 1860 tactaatcat catgaggact tttaaagttt ccatttggaa tcttgattac atcataaacc 1920 tcataattaa gaacttaagc aagtcactaa ctgagaataa atattctcaa ctagacgagg 1980 agcagccaat ggagattgat taaacgaaca tgaaaattat tcttttcttg gcactgataa 2040 cactcgctac ttgtgagctt tatcactacc aagagtgtgt tagaggtaca acagtacttt 2100 taaaagaacc ttgctcgtcg ggaacatacg agggcaattc accatttcat cctctagctg 2160 ataacaaatt tgcactgact tgctttagca ctcaatttgc ttttgcttgt cctgacggcg 2220 taaaacacgt ctatcagtta cgtgccagat cagtttcacc taaactgttc atcagacaag 2280 aggaagttca agaactttac tctccaattt ttcttattgt tgcggcaata gtgtttataa 2340 cactttgctt cacactcaaa agaaagacag aatgattgaa ctttcattaa ttgacttcta 2400 tttgtgcttt ttagcctttc tgctattcct tgttttaatt atgcttatta tcttttggtt 2460 ctcacttgaa ctgcaagatc ataatgaaac ttgtcacgcc taaacgaaca tgaaatttct 2520 tgttttctta ggaatcatca caactgtagc tgcatttcac caagaatgta gtttacagtc 2580 atgtactcaa catcaaccat atgtagttga tgacccgtgt cctattcact tctattctaa 2640 atggtatatc agagtaggag ctagaaaatc agcaccttta attgaattgt gcgtggatga 2700 ggctggttct aaatcaccca ttcagtacat cgatatcggt aattatacag tttcctgttt 2760 accttttaca attaactgcc aggaacctaa attgggtagt cttgtagtgc gttgttcgtt 2820 ctacgaggac tttttagagt atcatgacgt tcgtgttgtt ttagatttca tctaaacgaa 2880 caaactaaaa tgtctgataa tggacctcaa aatcagcgaa atgcacctcg cattacgttt 2940 ggtggaccat cagattcaac tggcagtaac cagaatggag aacgaagtgg tgcgcgatca 3000 aaacaacgcc gcccgcaagg tttacccaat aatactgcgt cttggttcac cgctctcact 3060 caacatggca aggaagattt aaaattccct cgaggacaag gcgttccaat taacaccaat 3120 agcagtccag atgaccaaat tggctactac cgccgcgcca caagacgaat tcgtggtggt 3180 gatggtaaaa tgaaagatct cagtccaaga tggtatttct actatctagg aactgggcca 3240 gaagctggac ttccttatgg tgctaacaaa gatggcatca tatgggttgc aactgaggga 3300 gccttgaata caccaaaaga tcacattggc accagaaatc ctgctaacaa tgctgcaatc 3360 gtgctacaac ttcctcaagg aacaacatta ccaaaaggtt tttacgcaga agggtctaga 3420 ggtggaagtc aagcctcttc tagatcatca tcacgtagtc gcaacagttc aagaaattca 3480 actccaggtt caagtagagg aacttctcct gctagaatgg ctggaaatgg aggtgatgct 3540 gctcttgctt tgttactact tgacagattg aaccagcttg agagcaaaat gtctggtaaa 3600 ggccaacaac aacaaggcca aactgtcact aagaaatctg ctgctgaggc ttctaagaag 3660 cctagacaaa aacgtactgc cactaaagca tacaatgtaa cacaagcttt cggcagacgt 3720 ggtccagaac aaactcaagg aaattttggg gatcaggaac taatcagaca aggaactgat 3780 tacaaacatt ggccgcaaat tgcacaattt gctccttctg cttcagcgtt ctttggaatg 3840 tcgagaattg gaatggaagt cacaccttcg ggaacatggt tgacctatac aggtgccatc 3900 aaattggatg acaaagatcc aaatttcaaa gatcaagtca ttttgctgaa taagcatatt 3960 gacgcataca aaacattccc accaacagag cctaaaaagg acaaaaagaa gaaggctgat 4020 gaaactcaag ccttaccgca gagacagaag aaacagcaaa ctgtgactct tcttcctgct 4080 gcagatttgg atgatttctc caaacaattg caacaatcca tgagcagtgc tgactcaact 4140 caggcctaaa ctcatgcaga ccacacaagg cagatgggct atataaacgt tttcgctttt 4200 ccgtttacga tatatagtct actcttgtgc agaatgaatt ctcgtaacta catagcacaa 4260 gtagatgtag ttaactttaa tctcacatag caatctttaa tcagtgtgta acattaggga 4320 ggacttgaaa gagccaccac attttcaccg aggccacgcg gagtacgatc gagtgtacag 4380 tgaacaatgc tagggagagc tgcctatatg gatgagccct aatgtgtaaa attaatttta 4440 gtagtgctat ccccatgtga ttttaatagc ttcttaggag aatgac 4486 <210> 20 <211> 275 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_ORF3a_Protein <400> 20 Met Asp Leu Phe Met Arg Ile Phe Thr Ile Gly Thr Val Thr Leu Lys 1 5 10 15 Gln Gly Glu Ile Lys Asp Ala Thr Pro Ser Asp Phe Val Arg Ala Thr 20 25 30 Ala Thr Ile Pro Ile Gln Ala Ser Leu Pro Phe Gly Trp Leu Ile Val 35 40 45 Gly Val Ala Leu Leu Ala Val Phe Gln Ser Ala Ser Lys Ile Ile Thr 50 55 60 Leu Lys Lys Arg Trp Gln Leu Ala Leu Ser Lys Gly Val His Phe Val 65 70 75 80 Cys Asn Leu Leu Leu Leu Phe Val Thr Val Tyr Ser His Leu Leu Leu 85 90 95 Val Ala Ala Gly Leu Glu Ala Pro Phe Leu Tyr Leu Tyr Ala Leu Val 100 105 110 Tyr Phe Leu Gln Ser Ile Asn Phe Val Arg Ile Ile Met Arg Leu Trp 115 120 125 Leu Cys Trp Lys Cys Arg Ser Lys Asn Pro Leu Leu Tyr Asp Ala Asn 130 135 140 Tyr Phe Leu Cys Trp His Thr Asn Cys Tyr Asp Tyr Cys Ile Pro Tyr 145 150 155 160 Asn Ser Val Thr Ser Ser Ile Val Ile Thr Ser Gly Asp Gly Thr Thr 165 170 175 Ser Pro Ile Ser Glu His Asp Tyr Gln Ile Gly Gly Tyr Thr Glu Lys 180 185 190 Trp Glu Ser Gly Val Lys Asp Cys Val Val Leu His Ser Tyr Phe Thr 195 200 205 Ser Asp Tyr Tyr Gln Leu Tyr Ser Thr Gln Leu Ser Thr Asp Thr Gly 210 215 220 Val Glu His Val Thr Phe Phe Ile Tyr Asn Lys Ile Val Asp Glu Pro 225 230 235 240 Glu Glu His Val Gln Ile His Thr Ile Asp Gly Ser Ser Gly Val Val 245 250 255 Asn Pro Val Met Glu Pro Ile Tyr Asp Glu Pro Thr Thr Thr Thr Ser 260 265 270 Val Pro Leu 275 <210> 21 <211> 75 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Structural_Protein_E <400> 21 Met Tyr Ser Phe Val Ser Glu Glu Thr Gly Thr Leu Ile Val Asn Ser 1 5 10 15 Val Leu Leu Phe Leu Ala Phe Val Val Phe Leu Leu Val Thr Leu Ala 20 25 30 Ile Leu Thr Ala Leu Arg Leu Cys Ala Tyr Cys Cys Asn Ile Val Asn 35 40 45 Val Ser Leu Val Lys Pro Ser Phe Tyr Val Tyr Ser Arg Val Lys Asn 50 55 60 Leu Asn Ser Ser Arg Val Pro Asp Leu Leu Val 65 70 75 <210> 22 <211> 222 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Membrane_Glycoprotein_M <400> 22 Met Ala Asp Ser Asn Gly Thr Ile Thr Val Glu Glu Leu Lys Lys Leu 1 5 10 15 Leu Glu Gln Trp Asn Leu Val Ile Gly Phe Leu Phe Leu Thr Trp Ile 20 25 30 Cys Leu Leu Gln Phe Ala Tyr Ala Asn Arg Asn Arg Phe Leu Tyr Ile 35 40 45 Ile Lys Leu Ile Phe Leu Trp Leu Leu Trp Pro Val Thr Leu Ala Cys 50 55 60 Phe Val Leu Ala Ala Val Tyr Arg Ile Asn Trp Ile Thr Gly Gly Ile 65 70 75 80 Ala Ile Ala Met Ala Cys Leu Val Gly Leu Met Trp Leu Ser Tyr Phe 85 90 95 Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser Phe 100 105 110 Asn Pro Glu Thr Asn Ile Leu Leu Asn Val Pro Leu His Gly Thr Ile 115 120 125 Leu Thr Arg Pro Leu Leu Glu Ser Glu Leu Val Ile Gly Ala Val Ile 130 135 140 Leu Arg Gly His Leu Arg Ile Ala Gly His His Leu Gly Arg Cys Asp 145 150 155 160 Ile Lys Asp Leu Pro Lys Glu Ile Thr Val Ala Thr Ser Arg Thr Leu 165 170 175 Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp Ser Gly 180 185 190 Phe Ala Ala Tyr Ser Arg Tyr Arg Ile Gly Asn Tyr Lys Leu Asn Thr 195 200 205 Asp His Ser Ser Ser Ser Asp Asn Ile Ala Leu Leu Val Gln 210 215 220 <210> 23 <211> 61 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_ORF6_Protein <400> 23 Met Phe His Leu Val Asp Phe Gln Val Thr Ile Ala Glu Ile Leu Leu 1 5 10 15 Ile Ile Met Arg Thr Phe Lys Val Ser Ile Trp Asn Leu Asp Tyr Ile 20 25 30 Ile Asn Leu Ile Ile Lys Asn Leu Ser Lys Ser Leu Thr Glu Asn Lys 35 40 45 Tyr Ser Gln Leu Asp Glu Glu Gln Pro Met Glu Ile Asp 50 55 60 <210> 24 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_ORF7a_Protein <400> 24 Met Lys Ile Ile Leu Phe Leu Ala Leu Ile Thr Leu Ala Thr Cys Glu 1 5 10 15 Leu Tyr His Tyr Gln Glu Cys Val Arg Gly Thr Thr Val Leu Leu Lys 20 25 30 Glu Pro Cys Ser Ser Gly Thr Tyr Glu Gly Asn Ser Pro Phe His Pro 35 40 45 Leu Ala Asp Asn Lys Phe Ala Leu Thr Cys Phe Ser Thr Gln Phe Ala 50 55 60 Phe Ala Cys Pro Asp Gly Val Lys His Val Tyr Gln Leu Arg Ala Arg 65 70 75 80 Ser Val Ser Pro Lys Leu Phe Ile Arg Gln Glu Glu Val Gln Glu Leu 85 90 95 Tyr Ser Pro Ile Phe Leu Ile Val Ala Ala Ile Val Phe Ile Thr Leu 100 105 110 Cys Phe Thr Leu Lys Arg Lys Thr Glu 115 120 <210> 25 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_ORF8_Protein <400> 25 Met Lys Phe Leu Val Phe Leu Gly Ile Ile Thr Thr Val Ala Ala Phe 1 5 10 15 His Gln Glu Cys Ser Leu Gln Ser Cys Thr Gln His Gln Pro Tyr Val 20 25 30 Val Asp Asp Pro Cys Pro Ile His Phe Tyr Ser Lys Trp Tyr Ile Arg 35 40 45 Val Gly Ala Arg Lys Ser Ala Pro Leu Ile Glu Leu Cys Val Asp Glu 50 55 60 Ala Gly Ser Lys Ser Pro Ile Gln Tyr Ile Asp Ile Gly Asn Tyr Thr 65 70 75 80 Val Ser Cys Leu Pro Phe Thr Ile Asn Cys Gln Glu Pro Lys Leu Gly 85 90 95 Ser Leu Val Val Arg Cys Ser Phe Tyr Glu Asp Phe Leu Glu Tyr His 100 105 110 Asp Val Arg Val Val Leu Asp Phe Ile 115 120 <210> 26 <211> 419 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Nulceocapsid_Phosphoprotein <400> 26 Met Ser Asp Asn Gly Pro Gln Asn Gln Arg Asn Ala Pro Arg Ile Thr 1 5 10 15 Phe Gly Gly Pro Ser Asp Ser Thr Gly Ser Asn Gln Asn Gly Glu Arg 20 25 30 Ser Gly Ala Arg Ser Lys Gln Arg Arg Pro Gln Gly Leu Pro Asn Asn 35 40 45 Thr Ala Ser Trp Phe Thr Ala Leu Thr Gln His Gly Lys Glu Asp Leu 50 55 60 Lys Phe Pro Arg Gly Gln Gly Val Pro Ile Asn Thr Asn Ser Ser Pro 65 70 75 80 Asp Asp Gln Ile Gly Tyr Tyr Arg Arg Ala Thr Arg Arg Ile Arg Gly 85 90 95 Gly Asp Gly Lys Met Lys Asp Leu Ser Pro Arg Trp Tyr Phe Tyr Tyr 100 105 110 Leu Gly Thr Gly Pro Glu Ala Gly Leu Pro Tyr Gly Ala Asn Lys Asp 115 120 125 Gly Ile Ile Trp Val Ala Thr Glu Gly Ala Leu Asn Thr Pro Lys Asp 130 135 140 His Ile Gly Thr Arg Asn Pro Ala Asn Asn Ala Ala Ile Val Leu Gln 145 150 155 160 Leu Pro Gln Gly Thr Thr Leu Pro Lys Gly Phe Tyr Ala Glu Gly Ser 165 170 175 Arg Gly Gly Ser Gln Ala Ser Ser Arg Ser Ser Ser Arg Ser Arg Asn 180 185 190 Ser Ser Arg Asn Ser Thr Pro Gly Ser Ser Arg Gly Thr Ser Pro Ala 195 200 205 Arg Met Ala Gly Asn Gly Gly Asp Ala Ala Leu Ala Leu Leu Leu Leu 210 215 220 Asp Arg Leu Asn Gln Leu Glu Ser Lys Met Ser Gly Lys Gly Gln Gln 225 230 235 240 Gln Gln Gly Gln Thr Val Thr Lys Lys Ser Ala Ala Glu Ala Ser Lys 245 250 255 Lys Pro Arg Gln Lys Arg Thr Ala Thr Lys Ala Tyr Asn Val Thr Gln 260 265 270 Ala Phe Gly Arg Arg Gly Pro Glu Gln Thr Gln Gly Asn Phe Gly Asp 275 280 285 Gln Glu Leu Ile Arg Gln Gly Thr Asp Tyr Lys His Trp Pro Gln Ile 290 295 300 Ala Gln Phe Ala Pro Ser Ala Ser Ala Phe Phe Gly Met Ser Arg Ile 305 310 315 320 Gly Met Glu Val Thr Pro Ser Gly Thr Trp Leu Thr Tyr Thr Gly Ala 325 330 335 Ile Lys Leu Asp Asp Lys Asp Pro Asn Phe Lys Asp Gln Val Ile Leu 340 345 350 Leu Asn Lys His Ile Asp Ala Tyr Lys Thr Phe Pro Pro Thr Glu Pro 355 360 365 Lys Lys Asp Lys Lys Lys Lys Ala Asp Glu Thr Gln Ala Leu Pro Gln 370 375 380 Arg Gln Lys Lys Gln Gln Thr Val Thr Leu Leu Pro Ala Ala Asp Leu 385 390 395 400 Asp Asp Phe Ser Lys Gln Leu Gln Gln Ser Met Ser Ser Ala Asp Ser 405 410 415 Thr Gln Ala <210> 27 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_ORF10_Protein <400> 27 Met Gly Tyr Ile Asn Val Phe Ala Phe Pro Phe Thr Ile Tyr Ser Leu 1 5 10 15 Leu Leu Cys Arg Met Asn Ser Arg Asn Tyr Ile Ala Gln Val Asp Val 20 25 30 Val Asn Phe Asn Leu Thr 35 <210> 28 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> T7_promotor <400> 28 taatacgact cactatag 18 <210> 29 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> PolyA-Element <400> 29 aaaaaaaaaa aaaaaaaaaa cggccg 26 <210> 30 <211> 21536 <212> DNA <213> Artificial Sequence <220> <223> COVAX-Polyprotein encoding sequence <400> 30 atggcaaaga tgggcaaata cggcctgggc ttcaaatggg ccccagaatt tccatggatg 60 cttccgaacg catcggagaa gttgggtaac cctgagaggt cagaggagga tgggttttgc 120 ccctctgctg cgcaagaacc gaaagttaaa ggaaaaactt tggttaatca cgtgagggtg 180 aattgtagcc ggcttccagc tttggaatgc tgtgttcagt ctgccataat ccgtgatatt 240 tttgtagatg aggatcccca gaaggtggag gcctcaacta tgatggcatt gcagttcggt 300 agtgccgtct tggttaagcc atccaagcgc ttgtctattc aggcatggac taatttgggt 360 gtgcttccca aaacagctgc catggggttg ttcaagcgcg tctgcctgtg taacaccagg 420 gagtgctctt gtgacgccca cgtggccttt caccttttta cggtccaacc cgatggtgta 480 tgcctgggta atggccgttt tataggctgg ttcgttccag tcacagccat accggagtat 540 gcgaagcagt ggttgcaacc ctggtccatc cttcttcgta agggtggtaa caaagggtct 600 gtgacatccg gccacttccg ccgcgctgtt accatgcctg tgtatgactt taatgtagag 660 gatgcttgtg aggaggttca tcttaacccg aagggtaagt actcctgcaa ggcgtatgcc 720 ctgctgaagg gctatcgcgg tgttaagccc atcctgtttg tggaccagta tggttgcgac 780 tatactggat gtctcgccaa gggtcttgag gactatggcg atctcacctt gagtgagatg 840 aaggagttgt tccctgtgtg gcgtgactcc ttggatagtg aagtccttgt ggcttggcac 900 gttgatcgag atcctcgggc tgctatgcgt ctgcagactc ttgctactgt acgttgcatt 960 gattatgtgg gccaaccgac cgaggatgtg gtggatggag atgtggtagt gcgtgagcct 1020 gctcatcttc tcgcagccaa tgccattgtt aaaagactcc cccgtttggt ggagactatg 1080 ctgtatacgg attcgtccgt tacagaattc tgttataaaa ccaagctgtg tgaatgcggt 1140 tttatcacgc agtttggcta tgtggattgt tgtggtgaca cctgtgattt tcgtgggtgg 1200 gttgccggca atatgatgga tggctttcca tgtccagggt gtaccaaaaa ttatatgccc 1260 tgggaattgg aggcccagtc atcaggtgtt ataccagaag gaggtgttct attcactcag 1320 agcactgata cagtgaatcg tgagtccttt aagctctacg gtcatgctgt tgtgcctttt 1380 ggttctgctg tgtattggag cccttgccca ggtatgtggc ttccagtaat ttggtcgtcg 1440 gttaagtcat actctggttt gacttataca ggagtagttg gttgtaaggc aattgttcaa 1500 gagacagacg ctatatgtcg ttctctgtat atggattatg tccagcacaa gtgtggcaat 1560 ctcgagcaga gagctatcct tggattggac gatgtctatc atagacagtt gcttgtgaat 1620 aggggtgact atagtctcct ccttgagaat gtggatttgt ttgttaagcg gcgcgctgaa 1680 tttgcttgca aattcgccac ctgtggagat ggtcttgtac ccctcctact agatggttta 1740 gtgccccgca gttattattt gattaagagt ggtcaagctt tcacctctat gatggttaat 1800 tttagccatg aggtgactga catgtgtatg gacatggctt tattgttcat gcatgatgtt 1860 aaagtggcca ctaagtatgt taagaaggtt actggcaaac tggccgtgcg ctttaaagcg 1920 ttgggtgtag ccgttgtcag aaaaattact gaatggtttg atttagccgt ggacattgct 1980 gctagtgccg ctggatggct ttgctaccag ctggtaaatg gcttatttgc agtggccaat 2040 ggtgttataa cctttgtaca ggaggtgcct gagcttgtca agaattttgt tgacaagttc 2100 aaggcatttt tcaaggtttt gatcgactct atgtcggttt ctatcttgtc tggacttact 2160 gttgtcaaga ctgcctcaaa tagggtgtgt cttgctggca gtaaggttta tgaagttgtg 2220 cagaaatctt tgtctgcata tgttatgcct gtgggttgca gcgaagccac ttgtttggtg 2280 ggtgagattg aacctgcagt ttttgaagat gatgttgttg atgtggttaa agccccatta 2340 acatatcaag gctgttgtaa gccacccact tctttcgaga agatttgtat tgtggataaa 2400 ttgtatatgg ccaagtgtgg tgatcaattt taccctgtgg ttgttgataa cgacactgtt 2460 ggcgtgttag atcagtgctg gaggtttccc tgtgcgggca agaaagtcga gtttaacgac 2520 aagcccaaag tcaggaagat accctccacc cgtaagatta agatcacctt cgcactggat 2580 gcgacctttg atagtgttct ttcgaaggcg tgttcagagt ttgaagttga taaagatgtt 2640 acattggatg agctgcttga tgttgtgctt gacgcagttg agagtacgct cagcccttgt 2700 aaggagcatg atgtgatagg cacaaaagtt tgtgctttac ttgataggtt ggcaggagat 2760 tatgtctatc tttttgatga gggaggcgat gaagtgatcg ccccgaggat gtattgttcc 2820 ttttctgctc ctgatgacga ggactgcgtt gcagcggatg ttgtagatgc agatgaaaac 2880 caagatgatg atgccgagga ctcagcagtc cttgtcgctg atacccaaga agaggacggc 2940 gttgccaagg ggcaggttga ggcggattcg gaaatttgcg ttgcgcatac tggtagtcaa 3000 gaagaattgg ctgagcctga tgctgtcgga tctcaaactc ccatcgcctc tgctgaggaa 3060 accgaagtcg gagaggcaag cgacagggaa gggattgctg aggcgaaggc aactgtgtgt 3120 gctgatgctg tagatgcctg ccccgatcaa gtggaggcat ttgaaattga aaaggtcgag 3180 gactctatct tggatgagct tcaaactgaa cttaatgcgc cagcggacaa gacctatgag 3240 gatgtcttgg cattcgatgc cgtatgctca gaggcgttgt ctgcattcta tgctgtgccg 3300 agtgatgaga cgcactttaa agtgtgtgga ttctattcgc ctgctataga gcgcactaat 3360 tgttggctgc gttctacttt gatagtaatg cagagtctac ctttggaatt taaagacttg 3420 gagatgcaaa agctctggtt gtcttacaag gccggctatg accaatgctt tgtggacaaa 3480 ctagttaaga gcgtgcccaa gtctattatc cttccacaag gtggttatgt ggcagatttt 3540 gcctatttct ttctaagcca gtgtagcttt aaagcttatg ctaactggcg ttgtttagag 3600 tgtgacatgg agttaaagct tcaaggcttg gacgccatgt ttttctatgg ggacgttgtg 3660 tctcatatgt gcaagtgtgg taatagcatg accttgttgt ctgcagatat accctacact 3720 ttgcattttg gagtgcgaga tgataagttt tgcgcttttt acacgccaag aaaggtcttt 3780 agggctgctt gtgcggtaga tgttaatgat tgtcactcta tggctgtagt agagggcaag 3840 caaattgatg gtaaagtggt taccaaattt attggtgaca aatttgattt tatggtgggt 3900 tacgggatga catttagtat gtctcctttt gaactcgccc agttatatgg ttcatgtata 3960 acaccaaatg tttgttttgt taaaggagat gttataaagg ttgttcgctt agttaatgct 4020 gaagtcattg ttaaccctgc taatgggcgt atggctcatg gtgccggcgt cgccggcgcc 4080 atagctgaaa aggcgggcag tgcttttatt aaagaaacct ccgatatggt gaaggctcag 4140 ggcgtttgcc aggttggtga atgctatgaa tctgccggtg gtaagttatg taaaaaggtg 4200 cttaacattg tagggccaga tgcgcgaggg catggcaagc aatgctattc acttttagag 4260 cgtgcttatc agcatattaa taagtgtgac aatgttgtca ctactttaat ttcggctggt 4320 atatttagtg tgcctactga tgtctcccta acttacttac ttggtgtagt gacaaagaat 4380 gtcattcttg tcagtaacaa ccaggatgat tttgatgtga tagagaagtg tcaggtgacc 4440 tccgttgctg gtaccaaagc gctatcactt caattggcca aaaatttgtg ccgtgatgta 4500 aagtttgtga cgaatgcatg tagttcgctt tttagtgaat cttgctttgt ctcaagctat 4560 gatgtgttgc aggaagttga agcgctgcga catgatatac aattggatga tgatgctcgt 4620 gtctttgtgc aggctaatat ggactgtctg cccacagact ggcgtctcgt taacaaattt 4680 gatagtgttg atggtgttag aaccattaag tattttgaat gcccgggcgg gatttttgta 4740 tccagccagg gcaaaaagtt tggttatgtt cagaatggtt catttaagga ggcgagtgtt 4800 agccaaataa gggctttact cgctaataag gttgatgtct tgtgtactgt tgatggtgtt 4860 aacttccgct cctgctgcgt agcagagggt gaagtttttg gcaagacatt aggttcagtc 4920 ttttgtgatg gcataaatgt caccaaagtt aggtgtagtg ccatttacaa gggtaaggtt 4980 ttctttcagt acagtgattt gtccgaggca gatcttgtgg ctgttaaaga tgcctttggt 5040 tttgatgaac cacaactgct gaagtactac actatgcttg gcatgtgtaa gtggccagta 5100 gttgtttgtg gcaattattt tgctttcaag cagtcaaata ataattgcta catcaacgtg 5160 gcatgtttaa tgctgcaaca cttgagttta aagtttccta agtggcaatg gcaagaggct 5220 tggaacgagt tccgctctgg taaaccacta aggtttgtgt ccttggtatt agcaaagggc 5280 agctttaaat ttaatgaacc ttctgattct atcgatttta tgcgtgtggt gctacgtgaa 5340 gcagatttga gtggtgccac gtgcaatttg gaatttgttt gtaaatgtgg tgtgaagcaa 5400 gagcagcgca aaggtgttga cgctgttatg cattttggta cgttggataa aggtgatctt 5460 gtcaggggtt ataatatcgc atgtacgtgc ggtagtaaac ttgtgcattg cacccaattt 5520 aacgtaccat ttttaatttg ctccaacaca ccagagggta ggaaactgcc cgacgatgtt 5580 gttgcagcta atatttttac tggtggtagt gtgggccatt acacgcatgt gaaatgtaaa 5640 cccaagtacc agctttatga tgcttgtaat gttaataagg tttcggaggc taagggtaat 5700 tttaccgatt gcctctacct taaaaattta aagcaaacct tctcgtctgt gctgacgact 5760 ttttatttag atgacgtaaa gtgtgtggag tataagccag atttatcgca gtattactgt 5820 gagtctggta aatattatac aaaacccatt attaaggccc aatttagaac atttgagaag 5880 gttgatggtg tctataccaa ctttaaattg gtgggacata gtattgctga aaaactcaat 5940 gctaagctgg gatttgattg taattctccc tttgtggagt ataaaattac agagtggcca 6000 acagctactg gagatgtggt gttggctagt gatgatttgt atgtaagtcg gtacttaagc 6060 gggtgcatta cttttggtaa accggttgtc tggcttggcc atgaggaagc atcgctgaaa 6120 tctctcacat attttaatag acctagtgtc gtttgtgaaa ataaatttaa cgtgttgccc 6180 gttgatgtca gtgaacccac ggacaagggg cctgtgcctg ctgcagtcct tgttaccggc 6240 gtccctggag ctgatgcgtc agctggtgcc ggtattgcca aggagcaaaa agcctgtgct 6300 tctgctagtg tggaggatca ggttgttacg gaggttcgtc aagagccatc tgtttcagct 6360 gctgatgtca aagaggttaa attgaatggt gttaaaaagc ctgttaaggt ggaaggtagt 6420 gtggttgtta atgatcccac tagcgaaacc aaagttgtta aaagtttgtc tattgttgat 6480 gtctatgata tgttcctgac agggtgtaag tatgtggttt ggactgctaa tgagttgtct 6540 cgactagtaa attcaccgac tgttagggag tatgtgaagt ggggtatggg aaagattgta 6600 acacccgcta agttgttgtt gttaagagat gagaagcaag agttcgtagc gccaaaagta 6660 gtcaaggcga aagctattgc ctgctattgt gctgtgaagt ggtttctcct ctattgtttt 6720 agttggataa agtttaatac tgacaataag gttatataca ccacagaagt agcttcaaag 6780 cttactttca agttgtgctg tttggccttt aagaatgcct tacagacgtt taattggagc 6840 gttgtgtcta ggggcttttt cctagttgca acggtctttt tactctggtt taactttttg 6900 tatgctaatg ttattttgag tgacttctat ttgcctaata ttgggcctct ccctacgttt 6960 gtgggacaga tagttgcgtg gtttaagact acatttggtg tgtcaaccat ctgtgatttc 7020 taccaggtga cggatttggg ctatagaagt tcgttttgta atggaagtat ggtatgtgaa 7080 ctatgcttct caggttttga tatgctggac aactatgatg ctataaatgt tgttcaacac 7140 gttgtagata ggcgtttgtc ctttgactat attagcctat ttaaactggt agttgagctt 7200 gtaatcggct actctcttta tactgtgtgc ttctacccac tgtttgtcct tattggaatg 7260 cagttattga ccacatggtt gcctgaattc tttatgctgg agactatgca ttggagtgct 7320 cgtttgtttg tgtttgttgc caatatgctt ccagctttta cgttactgcg attttacatc 7380 gtggtgacag ctatgtataa ggtctattgt ctttgtagac atgttatgta tggatgtagt 7440 aagcctggtt gcttgttttg ttataagaga aaccgtagtg tccgtgttaa gtgtagcacc 7500 gttgttggtg gttcactacg ctattacgat gtaatggcta acggcggcac aggtttctgt 7560 acaaagcacc agtggaactg tcttaattgc aattcctgga aaccaggcaa tacattcata 7620 actcatgaag cagcggcgga cctctctaag gagttgaaac gccctgtgaa tccaacagat 7680 tctgcttatt actcggtcac agaggttaag caggttggtt gttccatgcg tttgttctac 7740 gagagagatg gacagcgtgt ttatgatgat gttaatgcta gtttgtttgt ggacatgaat 7800 ggtctgctgc attctaaagt taaaggtgtg cctgaaacgc atgttgtggt tgttgagaat 7860 gaagctgata aagctggttt tctcggcgcc gcagtgtttt atgcacaatc gctctacaga 7920 cctatgttga tggtggaaaa gaaattaata actaccgcca acactggttt gtctgttagt 7980 cgaactatgt ttgaccttta tgtagattca ttgctgaacg tcctcgacgt ggatcgcaag 8040 agtctaacaa gttttgtaaa tgctgcgcac aactctctaa aggagggtgt tcagcttgaa 8100 caagttatgg atacctttat tggctgtgcc cgacgtaagt gtgctataga ttctgatgtt 8160 gaaaccaagt ctattaccaa gtccgtcatg tcggcagtaa atgctggcgt tgattttacg 8220 gatgagagtt gtaataactt ggtgcctacc tatgttaaaa gtgacactat cgttgcagcc 8280 gatttgggtg ttcttattca gaataatgct aagcatgtac aggctaatgt tgctaaagcc 8340 gctaatgtgg cttgcatttg gtctgtggat gcttttaacc agctatctgc tgacttacag 8400 cataggctgc gaaaagcatg ttcaaaaact ggcttgaaga ttaagcttac ttataataag 8460 caggaggcaa atgttcctat tttaactaca ccgttctctc ttaaaggggg cgctgttttt 8520 agtagaatgt tacaatggtt gtttgttgct aatttgattt gtttcattgt gttgtgggcc 8580 cttatgccaa catatgcagt gcacaaatcg gatatgcagt tgcctttata tgccagtttt 8640 aaagttatag ataacggtgt gctaagggat gtgtctgtta ctgacgcatg cttcgcaaac 8700 aaatttaatc aattcgacca atggtatgag tctacttttg gtcttgctta ttaccgcaac 8760 tctaaggctt gtcctgttgt ggttgctgta atagatcaag acattggcca taccttattt 8820 aatgttccta ccacagtttt aagatatgga tttcatgtgt tgcattttat aacccatgca 8880 tttgctactg atagcgtgca gtgttacacg ccacatatgc aaatccccta tgataatttc 8940 tatgctagtg gttgcgtgtt gtcatccctc tgtactatgc ttgcgcatgc agatggaacc 9000 ccgcatcctt attgttatac agggggtgtt atgcataatg cctctctgta tagttctttg 9060 gctcctcatg tccgttataa cctggctagt tcaaatggtt atatacgttt tcccgaagtg 9120 gttagtgaag gcattgtgcg tgttgtgcgc actcgctcta tgacctactg cagggttggt 9180 ttatgtgagg aggccgagga gggtatctgc tttaatttta atcgttcatg ggtattgaac 9240 aacccgtatt atagggccat gcctggaact ttttgtggta ggaatgcttt tgatttaata 9300 catcaagttt taggaggatt agtgcggcct attgatttct ttgccttaac ggcgagttca 9360 gtggctggtg ctatccttgc aattattgtc gttttggctt tctattattt aatcaagctt 9420 aagcgtgcct ttggtgacta cactagtgtt gtggttatca atgtaattgt gtggtgtata 9480 aattttctga tgctttttgt gtttcaggtt tatcccacat tgtcttgttt atatgcttgt 9540 ttctacttct acaccacgct ttatttccct tcggagataa gtgttgttat gcatttgcaa 9600 tggcttgtca tgtatggtgc tattatgccc ttgtggtttt gcattattta cgtggcagtc 9660 gttgtttcaa accatgcatt gtggttgttc tcttactgcc gcaaaattgg taccgaggtt 9720 cgtagtgacg gcacatttga ggaaatggcc cttactacct ttatgattac taaagaatct 9780 tattgtaagt tgaaaaactc tgtttctgat gttgctttta acaggtactt gagtctttac 9840 aacaagtacc gttacttcag tggcaaaatg gatactgccg cttatagaga ggctgcctgt 9900 tcacaactgg caaaggcaat ggaaacattt aaccataata atggtaatga tgttctctat 9960 cagcctccaa ccgcctctgt tactacatca tttttacagt ctggtatagt gaagatggtg 10020 tcgcccacct ctaaagtgga gccttgtatt gttagtgtta cttatggtaa catgacactt 10080 aatgggttgt ggttggatga taaagtttat tgcccaagac atgttatctg ttcttcagct 10140 gacatgacag accctgatta tcctaatttg ctttgtagag tgacatcaag tgatttttgt 10200 gttatgtctg gtcgtatgag ccttactgta atgtcttatc aaatgcaggg ctgccaactt 10260 gttttgactg ttacactgca aaatcctaac acgcctaagt attccttcgg tgttgttaag 10320 cctggtgaga catttactgt actggctgca tacaatggca gacctcaagg agccttccat 10380 gttacgcttc gtagtagcca taccataaag ggctcctttc tatgtggatc ctgcggttct 10440 gtaggatatg ttttaactgg cgatagtgta cgatttgttt atatgcatca gctagagttg 10500 agtactggtt gtcataccgg tactgacttt agtgggaact tttatggtcc ctatagagat 10560 gcgcaagttg tacaattgcc tgttcaggat tatacgcaga ctgttaatgt tgtagcttgg 10620 ctttatgctg ctatttttaa cagatgcaac tggtttgtgc aaagtgatag ttgttccctg 10680 gaggagttta atgtttgggc tatgaccaat ggttttagct caatcaaagc cgatcttgtc 10740 ttggatgcgc ttgcttctat gacaggcgtt acagttgaac aggtgttggc cgctattaag 10800 aggctgcatt ctggattcca gggcaaacaa attttaggta gttgtgtgct tgaagatgag 10860 ctgacaccaa gtgatgttta tcaacaacta gctggtgtca agctacagtc aaagcgcaca 10920 agagttataa aaggtacatg ttgctggata ttggcttcaa cgtttttgtt ctgtagcatt 10980 atctcagcat ttgtaaaatg gactatgttt atgtatgtta ctacccatat gttgggagtg 11040 acattgtgtg cactttgttt tgtaagcttt gctatgttgt tgatcaagca taagcatttg 11100 tatttaacta tgtacatcat gcctgtgtta tgcacactgt tttacaccaa ctatttggtt 11160 gtgtacaaac agagttttag aggtctagct tatgcttggc tttcacactt tgtccctgct 11220 gtagattata catatatgga tgaagtttta tatggtgttg tgttgctagt agctatggtg 11280 tttgttacca tgcgtagcat aaaccacgac gtcttttcta ttatgttctt ggttggtaga 11340 cttgtcagcc tggtatccat gtggtatttt ggagccaatt tagaggaaga ggtactattg 11400 ttcctcacat ccctatttgg cacgtacaca tggactacta tgttgtcatt ggctaccgct 11460 aaggttattg ctaaatggtt ggctgtgaat gtcttgtact tcacagacgt accgcaaatt 11520 aaattagttc tgttgagcta cttgtgtatt ggttatgtgt gttgttgtta ttggggaatc 11580 ttgtcactcc ttaatagcat ttttaggatg ccattgggcg tctacaatta taaaatctcc 11640 gttcaggagt tacgttatat gaatgctaat ggcttgcgcc cacctagaaa tagttttgag 11700 gccctgatgc ttaattttaa gctgttggga attggtggtg tgccagtcat tgaagtatct 11760 caaattcaat caagattgac ggatgttaaa tgtgctaatg ttgtgttgct taattgcctc 11820 cagcacttgc atattgcatc taattctaag ttgtggcagt attgtagtac tttgcacaat 11880 gaaatactgg ctacatctga tttgagcgtg gccttcgata agttggctca actcttagtt 11940 gttttatttg ctaatccagc agcagtggat agcaagtgcc ttgcaagtat tgaagaagtg 12000 agcgatgatt acgttcgcga caatactgtc ttgcaagcct tacagagtga atttgttaat 12060 atggctagct tcgttgagta tgaacttgct aagaagaatc tagatgaggc taaggctagc 12120 ggctctgcca atcaacagca gattaagcag ctagagaagg cgtgtaatat tgctaagtca 12180 gcatatgagc gcgacagagc tgttgctcgt aagctggaac gtatggctga tttagctctt 12240 acaaacatgt ataaagaagc tagaattaat gataagaaga gtaaggtagt gtctgcattg 12300 caaaccatgc tctttagtat ggtgcgtaag ctagataacc aagctcttaa ttctatttta 12360 gacaacgcag ttaagggttg tgtacctttg aatgcaatac catcattgac ttcgaacact 12420 ctgactataa tagtgccaga taagcaggtt tttgatcagg ttgtggataa tgtgtatgtc 12480 acctatgctg ggaatgtatg gcatatacag tttattcaag atgctgatgg tgctgttaaa 12540 caattgaatg agatagatgt taattcaacc tggcctctag tcattgctgc aaataggcat 12600 aatgaagtgt ctactgttgt tttgcagaac aatgagttga tgcctcagaa gttgagaact 12660 caggttgtca atagtggctc agatatgaat tgtaatactc ctacccagtg ttactataat 12720 actactggca cgggtaagat tgtgtatgct atacttagtg actgtgacgg cctgaagtac 12780 actaagatag taaaagaaga tggaaattgt gttgttttgg aattggatcc tccctgtaag 12840 ttttctgttc aggatgtgaa gggccttaaa attaagtacc tttactttgt gaaggggtgt 12900 aatacactgg ctagaggctg ggttgtaggc accttatcct cgacagtgag attgcaggcg 12960 ggtacggcaa ctgagtatgc ctccaactct gcaatactgt cgctgtgtgc gttttctgta 13020 gatcctaaga aaacgtactt ggattatata aaacagggtg gagttcccgt tactaattgt 13080 gttaagatgt tatgtgacca tgctggcact ggtatggcca ttactattaa gccggaggca 13140 accactaatc aggattctta tggtggtgct tccgtttgta tatattgccg ctcgcgtgtt 13200 gaacatccag atgttgatgg attgtgcaaa ttacgcggca agtttgtcca agtgccctta 13260 ggcataaaag atcctgtgtc atatgtgttg acgcatgatg tttgtcaggt ttgtggcttt 13320 tggcgagatg gtagctgttc ctgtgtaggc acaggctccc agtttcagtc aaaagacacg 13380 aactttttaa acggattcgg ggtacaagtg taaatgcccg tcttgtaccc tgtgccagtg 13440 gcttggacac tgatgttcaa ttaagggcat ttgacatttg taatgctaat cgagctggca 13500 ttggtttgta ttataaagtg aattgctgcc gcttccagcg tgtagatgag gacggcaaca 13560 agttggataa gttctttgtt gttaaaagaa ctaatttaga agtgtataac aaggagaaag 13620 aatgctatga gttgacaaaa gaatgcggtg ttgtggctga acacgagttc ttcacatttg 13680 atgtggaggg aagtcgggta ccacacatag tccgtaaaga tctttcaaag tttactatgt 13740 tagatctttg ctatgcattg cgtcattttg accgcaatga ttgttcaact cttaaggaaa 13800 ttctccttac atatgctgag tgtgaagagt cctacttcca aaagaaggac tggtatgatt 13860 ttgttgagaa tcctgatata attaatgtgt acaagaagct tggtcctata tttaatagag 13920 ccctgcttaa cactgccaag tttgcagacg cattagtgga ggcaggctta gtaggtgttt 13980 taacacttga taatcaagat ttatatggtc aatggtatga ctttggagat tttgtcaaga 14040 cagtacctgg ttgtggtgtt gccgtggcag actcttatta ttcatatatg atgccaatgc 14100 tgactatgtg tcatgcgttg gatagtgagt tgtttgttaa tggtacttat agggagtttg 14160 accttgttca gtatgatttt actgatttca agctagagct gttcactaag tattttaagc 14220 attggagtat gacctaccac ccgaacacct gtgagtgcga ggatgacagg tgcattattc 14280 attgcgccaa ttttaatata cttttcagca tggtcttacc taagacctgt tttgggcctc 14340 ttgttaggca gatatttgtg gatggtgttc ctttcgttgt gtcgatcggt taccattata 14400 aagaattagg tgttgttatg aatatggatg tggatacaca tcgttatcgc ttgtctctta 14460 aggacttgct tttgtatgct gcagaccctg cccttcatgt ggcgtctgct agtgcactgc 14520 ttgatttgcg cacatgttgt tttagcgttg cagctattac aagtggcgta aaatttcaaa 14580 cagttaaacc tggaaatttt aatcaggatt tctacgagtt tattttgagt aaaggcctgc 14640 ttaaagaggg gagctccgtt gatttgaagc acttcttctt tacgcaggat ggtaatgctg 14700 ctattactga ttacaattac tacaagtata atctacccac catggtggat attaagcagt 14760 tgttgtttgt tttagaagtt gttaataagt acttcgagat ctatgagggt gggtgtatac 14820 ccgcaacaca ggtcattgtt aataattatg acaagagtgc tggctatcca tttaataaat 14880 ttggaaaggc caggctctat tatgaggcat tatcatttga ggagcaggat gaaatttatg 14940 cgtataccaa acgcaatgtc ctgccgaccc taactcaaat gaatcttaaa tatgctatta 15000 gtgctaagaa tagggcccgc accgttgctg gtgtctctat tctcagtact atgactggca 15060 gaatgtttca tcaaaagtgt ctaaagagta tagcagctac tcgcggtgtt cctgtagtta 15120 taggcaccac gaagttctat ggcggttggg atgatatgtt acgccgcctt attaaagatg 15180 ttgatagtcc tgtactcatg ggttgggact atcctaaatg tgatcgtgct atgccaaaca 15240 tactgcgtat tgttagtagt ttggtgctag cccgtaaaca tgattcgtgc tgttcgcata 15300 cggatagatt ctatcgtctt gcgaacgagt gcgcccaagt tttgagtgaa attgttatgt 15360 gtggtggttg ttattatgtt aaaccaggtg gcactagtag tggggatgca accactgctt 15420 ttgctaattc tgtgtttaac atttgtcaag ctgtttccgc caatgtatgc tcgcttatgg 15480 catgcaatgg acacaaaatt gaagatttga gtatacgcga gttacaaaag cgcctatact 15540 ctaatgtcta tcgtgcggac catgttgacc ccgcatttgt tagtgagtat tatgagtttt 15600 taaacaagca ttttagtatg atgattttga gtgatgatgg tgttgtgtgt tataattcag 15660 agtttgcgtc caagggttat attgctaata taagtgcctt tcaacaggta ttatattatc 15720 aaaacaacgt gtttatgtct gaggccaaat gttgggtaga aacagacatc gaaaagggac 15780 cgcatgaatt ttgttctcaa catacaatgc tagtcaagat ggatggtgat gaagtctacc 15840 ttccataccc tgatccttcg agaatcttag gagcaggctg ttttgttgat gatttactca 15900 agactgatag cgttctcttg atagagcgtt tcgtaagtct tgcaattgat gcttatcctt 15960 tagtatacca tgagaaccca gagtatcaaa atgtgttccg ggtatattta gaatacatca 16020 agaagctgta caatgatctc ggtaatcaga tcctggacag ctacagtgtt attttaagta 16080 cttgtgatgg tcaaaagttt actgacgaga cgttttacaa gaacatgtat ttaagaagtg 16140 cagtgctgca aagcgttggt gcctgcgttg tctgtagttc tcaaacatca ttacgttgtg 16200 gcagttgcat acgcaagcct ttgctgtgtt gcaaatgcgc ctatgatcat gttatgtcca 16260 ctgatcataa atatgtcctg agtgtgtcac catatgtgtg taattcaccg ggatgtgatg 16320 taaatgatgt taccaaattg tatttaggtg gtatgtcata ttattgtgag gaccataaac 16380 cacagtattc attcaaattg gtgatgaatg gtatggtttt tggtttatat aagcagtctt 16440 gtactggttc gccctacata gaggatttta ataaaatcgc tagttgcaaa tggacagaag 16500 tcgatgatta tgtgctagct aatgaatgca ccgaacgcct taaattgttt gccgcagaaa 16560 cgcagaaggc cacagaagag gcctttaagc aatgttatgc gtcagcaacg atccgtgaga 16620 tcgtgagcga tcgggagtta attttatctt gggaaattgg taaagtccgc ccgccactta 16680 ataaaaatta cgtgttcacc ggctaccatt ttactaataa tggtaagaca gttttaggtg 16740 agtatgtttt tgataagagt gagttgacta atggtgtgta ttatcgcgcc acaaccactt 16800 ataagttatc tgtaggtgat gtgttcattt taacatcaca cgcagtgtct agtttaagtg 16860 ctcctacatt agtaccgcag gagaattata ctagcattcg ttttgctagt gtttatagtg 16920 tgcctgagac gtttcagaat aatgtgccta attatcagca cattggaatg aagcgctatt 16980 gtactgtaca gggaccgcct ggtactggta agtcccatct agccattggg ctagctgttt 17040 attattgtac agcgcgcgtg gtgtataccg ctgctagcca tgctgcagtt gacgcgctgt 17100 gtgaaaaggc acataaattt ctcaacatca acgactgcac gcgtattgtt cctgcaaagg 17160 tgcgtgtaga ttgttatgat aaattcaagg tcaatgacac cactcgcaag tatgtgttta 17220 ctacaataaa tgcattacct gagttggtga ctgacattat tgtcgttgat gaagttagta 17280 tgcttaccaa ctatgagctg tctgttatta acagtcgtgt tagggctaag cattatgtgt 17340 atattggcga cccggcgcag ttacctgcac cacgtgtgct actgaataag ggaactctag 17400 aacctagata ttttaattcc gttaccaagc taatgtgttg tttgggtcca gatattttct 17460 tgggcacctg ttatagatgc cctaaggaga ttgtggatac ggtgtcagcc ttggtttata 17520 ataataagct gaaggctaaa aatgataata gctccatgtg ctttaaggtt tattataagg 17580 gccagactac acatgagagt tctagtgctg ttaatatgca gcaaatacat ttaatttcca 17640 agtttctgaa ggcaaacccc agttggagta acgccgtatt tattagtcct tataactcgc 17700 agaactatgt tgctaagaga gtcttgggat tacaaaccca gacagtagac tcagcgcagg 17760 gttctgaata tgattttgtt atctactcac agactgcgga aacagcgcat tctgtcaatg 17820 taaatagatt caatgttgct attacacgtg ctaagaaggg tattctctgt gtcatgagta 17880 gtatgcaatt atttgagtct cttaatttta ctacactgac gttggataag attaacaatc 17940 cacgattaca gtgtactaca aatttgttta aggattgtag caggagctat gtaggatatc 18000 acccagccca tgcaccatcc tttttggcag ttgatgacaa atataaggta ggcggtgatt 18060 tagccgtttg ccttaatgtt gctgattctg ctgtcactta ttcgcggctt atatcactca 18120 tgggattcaa gcttgacttg acccttgatg gttattgtaa gctgtttata actagagatg 18180 aagctatcaa acgtgttaga gcctgggttg gcttcgatgc agaaggtgcc catgcgatac 18240 gtgatagcat tgggacaaat ttcccattac aattaggctt ttcgactgga attgattttg 18300 ttgtcgaagc cactggaatg tttgctgaga gagatggtta tgtctttaaa aaggcagccg 18360 cacgagctcc tcctggcgaa caatttaaac accttatccc acttatgtca agagggcaga 18420 aatgggatgt ggttcgcatt agaatagtac aaatgttgtc agaccaccta gtggatttgg 18480 cagacagtgt tgtacttgtg acgtgggctg ccagctttga gctcacatgt ttgcgatatt 18540 tcgctaaagt tggaagagaa gttgtgtgta gtgtctgcac caagcgtgcg acatgtttta 18600 attctagaac tggatactat ggatgctggc gacatagtta ttcctgtgat tacctgtaca 18660 acccactaat agttgacatt caacagtggg gatatacagg atctttaact agcaatcatg 18720 atcctatttg cagcgtgcat aagggtgctc atgttgcatc atctgatgct atcatgaccc 18780 ggtgtctagc tgttcatgat tgcttttgta agtctgttaa ttggaattta gaatacccca 18840 ttatttcaaa tgaggtcagt gttaatacct cctgcaggtt attgcagcgc gtaatgttta 18900 gggctgcgat gctatgcaat aggtatgatg tgtgttatga cattggcaac cctaaaggtc 18960 ttgcctgtgt caaaggatat gattttaagt tctatgacgc ctcccctgtt gttaagtctg 19020 ttaaacagtt tgtttacaaa tacgaggcac ataaagatca atttttagat ggtttgtgta 19080 tgttttggaa ctgcaatgtg gataagtatc cagcgaatgc agttgtgtgt aggtttgaca 19140 cgcgtgtgtt gaacaaatta aatctccctg gctgtaatgg tggcagtttg tatgttaaca 19200 aacatgcatt ccacaccagt ccctttaccc gggctgcctt cgagaatttg aagcctatgc 19260 ctttctttta ttattcagat acgccctgtg tgtatatgga aggcatggaa tctaagcagg 19320 tcgattatgt cccattgaga agcgctacat gcatcacaag atgcaattta ggtggcgctg 19380 tttgtttaaa acatgctgag gagtatcgtg agtaccttga gtcttacaat acggcaacca 19440 cagcgggttt tactttttgg gtctataaga cttttgattt ttacaacctt tggaatactt 19500 ttactaggct ccaaagttta gaaaatgtag tgtataacct ggtcaacgct ggacactttg 19560 atggccgggc gggtgaactg ccttgtgctg ttataggtga gaaagtcatt gccaagattc 19620 aaaatgagga tgtcgtggtc tttaaaaata acacgccatt ccccactaat gtggctgtcg 19680 aattatttgc taagcgcagt attcggcccc accccgagct taagctcttt agaaatttga 19740 atattgacgt gtgctggagt cacgtccttt gggattatgc taaggatagt gtgttttgca 19800 gttcgacgta taaggtctgc aaatacacag atttacagtg cattgaaagc ttgaatgtac 19860 tttttgatgg tcgtgataat ggtgctcttg aagcttttaa gaagtgccgg aatggcgtct 19920 acattaacac gacaaaaatt aaaagtctgt cgatgattaa aggcccacaa cgtgccgatt 19980 tgaatggcgt agttgtggag aaagttggag attctgatgt ggaattttgg tttgctgtgc 20040 gtaaagacgg tgacgatgtt atcttcagcc gtacagggag ccttgaaccg agccattacc 20100 ggagcccaca aggtaatccg ggtggtaatc gcgtgggtga tctcagcggt aatgaagctc 20160 tagcgcgtgg cactatcttt actcaaagca gattattatc ttctttcaca cctcgatcag 20220 agatggagaa agattttatg gatttagatg atgatgtgtt cattgcaaaa tatagtttac 20280 aggactacgc gtttgaacac gttgtttatg gtagttttaa ccagaagatt attggaggtt 20340 tgcatttgct tattggctta gcccgtaggc agcaaaaatc caatctggta attcaagagt 20400 tcgtgacata cgactctagc attcattcgt actttatcac tgacgagaac agtggtagta 20460 gtaagagtgt gtgcactgtt attgatttat tgttagatga ttttgtggac attgtaaagt 20520 ccctgaatct aaagtgtgtg agtaaggttg ttaatgttaa tgtggatttt aaggacttcc 20580 agtttatgtt gtggtgcaat gaggagaagg tcatgacttt ctatcctcgt ttgcaggctg 20640 ctgctgactg gaaacctggt tatgttatgc ctgtcttata taagtatttg gaatcgcctc 20700 tggaaagagt aaacctctgg aattatggca agccgattac tttacctaca ggatgtatga 20760 tgaatgttgc taagtatact caattatgtc aatatttgag cactacaaca ttagcagttc 20820 cggctaatat gcgtgtctta caccttggtg ccggttcgga taagggtgtt gcccctgggt 20880 ctgcagttct taggcagtgg ctaccagcgg gaagtattct tgtagataat gatgtgaatc 20940 catttgtgag tgacagtgtc gcctcatatt atggaaattg tataacctta ccctttgatt 21000 gtcagtggga tctgataatt tctgatatgt acgaccctct tactaagaac attggggagt 21060 acaacgtgag taaagatgga ttctttactt acctctgtca tttaattcgt gacaagttgg 21120 ctctgggtgg cagtgttgcc ataaaaataa cagagttttc ttggaacgct gagttatata 21180 gtttaatggg gaagtttgcg ttctggacaa tcttttgcac caacgtaaac gcctcttcaa 21240 gtgaaggatt tttgattggc ataaattggt tgaataagac ccgtaccgaa attgacggta 21300 aaaccatgca tgccaattat ctgttttgga gaaatagtac aatgtggaat ggaggggctt 21360 acagtctctt tgacatgagt aagttccctt tgaaagcggc tggtacggct gttgttagcc 21420 ttaaaccaga ccaaataaat gacttagtcc tctccttgat tgagaagggc aagttattag 21480 tgcgtgatac acgcaaagaa gtttttgttg gcgatagcct agtaaatgtc aaataa 21536 <210> 31 <211> 4470 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Replicative_Polyprotein_1a <400> 31 Met Ala Lys Met Gly Lys Tyr Gly Leu Gly Phe Lys Trp Ala Pro Glu 1 5 10 15 Phe Pro Trp Met Leu Pro Asn Ala Ser Glu Lys Leu Gly Asn Pro Glu 20 25 30 Arg Ser Glu Glu Asp Gly Phe Cys Pro Ser Ala Ala Gln Glu Pro Lys 35 40 45 Val Lys Gly Lys Thr Leu Val Asn His Val Arg Val Asn Cys Ser Arg 50 55 60 Leu Pro Ala Leu Glu Cys Cys Val Gln Ser Ala Ile Ile Arg Asp Ile 65 70 75 80 Phe Val Asp Glu Asp Pro Gln Lys Val Glu Ala Ser Thr Met Met Ala 85 90 95 Leu Gln Phe Gly Ser Ala Val Leu Val Lys Pro Ser Lys Arg Leu Ser 100 105 110 Ile Gln Ala Trp Thr Asn Leu Gly Val Leu Pro Lys Thr Ala Ala Met 115 120 125 Gly Leu Phe Lys Arg Val Cys Leu Cys Asn Thr Arg Glu Cys Ser Cys 130 135 140 Asp Ala His Val Ala Phe His Leu Phe Thr Val Gln Pro Asp Gly Val 145 150 155 160 Cys Leu Gly Asn Gly Arg Phe Ile Gly Trp Phe Val Pro Val Thr Ala 165 170 175 Ile Pro Glu Tyr Ala Lys Gln Trp Leu Gln Pro Trp Ser Ile Leu Leu 180 185 190 Arg Lys Gly Gly Asn Lys Gly Ser Val Thr Ser Gly His Phe Arg Arg 195 200 205 Ala Val Thr Met Pro Val Tyr Asp Phe Asn Val Glu Asp Ala Cys Glu 210 215 220 Glu Val His Leu Asn Pro Lys Gly Lys Tyr Ser Cys Lys Ala Tyr Ala 225 230 235 240 Leu Leu Lys Gly Tyr Arg Gly Val Lys Pro Ile Leu Phe Val Asp Gln 245 250 255 Tyr Gly Cys Asp Tyr Thr Gly Cys Leu Ala Lys Gly Leu Glu Asp Tyr 260 265 270 Gly Asp Leu Thr Leu Ser Glu Met Lys Glu Leu Phe Pro Val Trp Arg 275 280 285 Asp Ser Leu Asp Ser Glu Val Leu Val Ala Trp His Val Asp Arg Asp 290 295 300 Pro Arg Ala Ala Met Arg Leu Gln Thr Leu Ala Thr Val Arg Cys Ile 305 310 315 320 Asp Tyr Val Gly Gln Pro Thr Glu Asp Val Val Asp Gly Asp Val Val 325 330 335 Val Arg Glu Pro Ala His Leu Leu Ala Ala Asn Ala Ile Val Lys Arg 340 345 350 Leu Pro Arg Leu Val Glu Thr Met Leu Tyr Thr Asp Ser Ser Val Thr 355 360 365 Glu Phe Cys Tyr Lys Thr Lys Leu Cys Glu Cys Gly Phe Ile Thr Gln 370 375 380 Phe Gly Tyr Val Asp Cys Cys Gly Asp Thr Cys Asp Phe Arg Gly Trp 385 390 395 400 Val Ala Gly Asn Met Met Asp Gly Phe Pro Cys Pro Gly Cys Thr Lys 405 410 415 Asn Tyr Met Pro Trp Glu Leu Glu Ala Gln Ser Ser Gly Val Ile Pro 420 425 430 Glu Gly Gly Val Leu Phe Thr Gln Ser Thr Asp Thr Val Asn Arg Glu 435 440 445 Ser Phe Lys Leu Tyr Gly His Ala Val Val Pro Phe Gly Ser Ala Val 450 455 460 Tyr Trp Ser Pro Cys Pro Gly Met Trp Leu Pro Val Ile Trp Ser Ser 465 470 475 480 Val Lys Ser Tyr Ser Gly Leu Thr Tyr Thr Gly Val Val Gly Cys Lys 485 490 495 Ala Ile Val Gln Glu Thr Asp Ala Ile Cys Arg Ser Leu Tyr Met Asp 500 505 510 Tyr Val Gln His Lys Cys Gly Asn Leu Glu Gln Arg Ala Ile Leu Gly 515 520 525 Leu Asp Asp Val Tyr His Arg Gln Leu Leu Val Asn Arg Gly Asp Tyr 530 535 540 Ser Leu Leu Leu Glu Asn Val Asp Leu Phe Val Lys Arg Arg Ala Glu 545 550 555 560 Phe Ala Cys Lys Phe Ala Thr Cys Gly Asp Gly Leu Val Pro Leu Leu 565 570 575 Leu Asp Gly Leu Val Pro Arg Ser Tyr Tyr Leu Ile Lys Ser Gly Gln 580 585 590 Ala Phe Thr Ser Met Met Val Asn Phe Ser His Glu Val Thr Asp Met 595 600 605 Cys Met Asp Met Ala Leu Leu Phe Met His Asp Val Lys Val Ala Thr 610 615 620 Lys Tyr Val Lys Lys Val Thr Gly Lys Leu Ala Val Arg Phe Lys Ala 625 630 635 640 Leu Gly Val Ala Val Val Arg Lys Ile Thr Glu Trp Phe Asp Leu Ala 645 650 655 Val Asp Ile Ala Ala Ser Ala Ala Gly Trp Leu Cys Tyr Gln Leu Val 660 665 670 Asn Gly Leu Phe Ala Val Ala Asn Gly Val Ile Thr Phe Val Gln Glu 675 680 685 Val Pro Glu Leu Val Lys Asn Phe Val Asp Lys Phe Lys Ala Phe Phe 690 695 700 Lys Val Leu Ile Asp Ser Met Ser Val Ser Ile Leu Ser Gly Leu Thr 705 710 715 720 Val Val Lys Thr Ala Ser Asn Arg Val Cys Leu Ala Gly Ser Lys Val 725 730 735 Tyr Glu Val Val Gln Lys Ser Leu Ser Ala Tyr Val Met Pro Val Gly 740 745 750 Cys Ser Glu Ala Thr Cys Leu Val Gly Glu Ile Glu Pro Ala Val Phe 755 760 765 Glu Asp Asp Val Val Asp Val Val Lys Ala Pro Leu Thr Tyr Gln Gly 770 775 780 Cys Cys Lys Pro Pro Thr Ser Phe Glu Lys Ile Cys Ile Val Asp Lys 785 790 795 800 Leu Tyr Met Ala Lys Cys Gly Asp Gln Phe Tyr Pro Val Val Val Asp 805 810 815 Asn Asp Thr Val Gly Val Leu Asp Gln Cys Trp Arg Phe Pro Cys Ala 820 825 830 Gly Lys Lys Val Glu Phe Asn Asp Lys Pro Lys Val Arg Lys Ile Pro 835 840 845 Ser Thr Arg Lys Ile Lys Ile Thr Phe Ala Leu Asp Ala Thr Phe Asp 850 855 860 Ser Val Leu Ser Lys Ala Cys Ser Glu Phe Glu Val Asp Lys Asp Val 865 870 875 880 Thr Leu Asp Glu Leu Leu Asp Val Val Leu Asp Ala Val Glu Ser Thr 885 890 895 Leu Ser Pro Cys Lys Glu His Asp Val Ile Gly Thr Lys Val Cys Ala 900 905 910 Leu Leu Asp Arg Leu Ala Gly Asp Tyr Val Tyr Leu Phe Asp Glu Gly 915 920 925 Gly Asp Glu Val Ile Ala Pro Arg Met Tyr Cys Ser Phe Ser Ala Pro 930 935 940 Asp Asp Glu Asp Cys Val Ala Ala Asp Val Val Asp Ala Asp Glu Asn 945 950 955 960 Gln Asp Asp Asp Ala Glu Asp Ser Ala Val Leu Val Ala Asp Thr Gln 965 970 975 Glu Glu Asp Gly Val Ala Lys Gly Gln Val Glu Ala Asp Ser Glu Ile 980 985 990 Cys Val Ala His Thr Gly Ser Gln Glu Glu Leu Ala Glu Pro Asp Ala 995 1000 1005 Val Gly Ser Gln Thr Pro Ile Ala Ser Ala Glu Glu Thr Glu Val Gly 1010 1015 1020 Glu Ala Ser Asp Arg Glu Gly Ile Ala Glu Ala Lys Ala Thr Val Cys 1025 1030 1035 1040 Ala Asp Ala Val Asp Ala Cys Pro Asp Gln Val Glu Ala Phe Glu Ile 1045 1050 1055 Glu Lys Val Glu Asp Ser Ile Leu Asp Glu Leu Gln Thr Glu Leu Asn 1060 1065 1070 Ala Pro Ala Asp Lys Thr Tyr Glu Asp Val Leu Ala Phe Asp Ala Val 1075 1080 1085 Cys Ser Glu Ala Leu Ser Ala Phe Tyr Ala Val Pro Ser Asp Glu Thr 1090 1095 1100 His Phe Lys Val Cys Gly Phe Tyr Ser Pro Ala Ile Glu Arg Thr Asn 1105 1110 1115 1120 Cys Trp Leu Arg Ser Thr Leu Ile Val Met Gln Ser Leu Pro Leu Glu 1125 1130 1135 Phe Lys Asp Leu Glu Met Gln Lys Leu Trp Leu Ser Tyr Lys Ala Gly 1140 1145 1150 Tyr Asp Gln Cys Phe Val Asp Lys Leu Val Lys Ser Val Pro Lys Ser 1155 1160 1165 Ile Ile Leu Pro Gln Gly Gly Tyr Val Ala Asp Phe Ala Tyr Phe Phe 1170 1175 1180 Leu Ser Gln Cys Ser Phe Lys Ala Tyr Ala Asn Trp Arg Cys Leu Glu 1185 1190 1195 1200 Cys Asp Met Glu Leu Lys Leu Gln Gly Leu Asp Ala Met Phe Phe Tyr 1205 1210 1215 Gly Asp Val Val Ser His Met Cys Lys Cys Gly Asn Ser Met Thr Leu 1220 1225 1230 Leu Ser Ala Asp Ile Pro Tyr Thr Leu His Phe Gly Val Arg Asp Asp 1235 1240 1245 Lys Phe Cys Ala Phe Tyr Thr Pro Arg Lys Val Phe Arg Ala Ala Cys 1250 1255 1260 Ala Val Asp Val Asn Asp Cys His Ser Met Ala Val Val Glu Gly Lys 1265 1270 1275 1280 Gln Ile Asp Gly Lys Val Val Thr Lys Phe Ile Gly Asp Lys Phe Asp 1285 1290 1295 Phe Met Val Gly Tyr Gly Met Thr Phe Ser Met Ser Pro Phe Glu Leu 1300 1305 1310 Ala Gln Leu Tyr Gly Ser Cys Ile Thr Pro Asn Val Cys Phe Val Lys 1315 1320 1325 Gly Asp Val Ile Lys Val Val Arg Leu Val Asn Ala Glu Val Ile Val 1330 1335 1340 Asn Pro Ala Asn Gly Arg Met Ala His Gly Ala Gly Val Ala Gly Ala 1345 1350 1355 1360 Ile Ala Glu Lys Ala Gly Ser Ala Phe Ile Lys Glu Thr Ser Asp Met 1365 1370 1375 Val Lys Ala Gln Gly Val Cys Gln Val Gly Glu Cys Tyr Glu Ser Ala 1380 1385 1390 Gly Gly Lys Leu Cys Lys Lys Val Leu Asn Ile Val Gly Pro Asp Ala 1395 1400 1405 Arg Gly His Gly Lys Gln Cys Tyr Ser Leu Leu Glu Arg Ala Tyr Gln 1410 1415 1420 His Ile Asn Lys Cys Asp Asn Val Val Thr Thr Leu Ile Ser Ala Gly 1425 1430 1435 1440 Ile Phe Ser Val Pro Thr Asp Val Ser Leu Thr Tyr Leu Leu Gly Val 1445 1450 1455 Val Thr Lys Asn Val Ile Leu Val Ser Asn Asn Gln Asp Asp Phe Asp 1460 1465 1470 Val Ile Glu Lys Cys Gln Val Thr Ser Val Ala Gly Thr Lys Ala Leu 1475 1480 1485 Ser Leu Gln Leu Ala Lys Asn Leu Cys Arg Asp Val Lys Phe Val Thr 1490 1495 1500 Asn Ala Cys Ser Ser Leu Phe Ser Glu Ser Cys Phe Val Ser Ser Tyr 1505 1510 1515 1520 Asp Val Leu Gln Glu Val Glu Ala Leu Arg His Asp Ile Gln Leu Asp 1525 1530 1535 Asp Asp Ala Arg Val Phe Val Gln Ala Asn Met Asp Cys Leu Pro Thr 1540 1545 1550 Asp Trp Arg Leu Val Asn Lys Phe Asp Ser Val Asp Gly Val Arg Thr 1555 1560 1565 Ile Lys Tyr Phe Glu Cys Pro Gly Gly Ile Phe Val Ser Ser Gln Gly 1570 1575 1580 Lys Lys Phe Gly Tyr Val Gln Asn Gly Ser Phe Lys Glu Ala Ser Val 1585 1590 1595 1600 Ser Gln Ile Arg Ala Leu Leu Ala Asn Lys Val Asp Val Leu Cys Thr 1605 1610 1615 Val Asp Gly Val Asn Phe Arg Ser Cys Cys Val Ala Glu Gly Glu Val 1620 1625 1630 Phe Gly Lys Thr Leu Gly Ser Val Phe Cys Asp Gly Ile Asn Val Thr 1635 1640 1645 Lys Val Arg Cys Ser Ala Ile Tyr Lys Gly Lys Val Phe Phe Gln Tyr 1650 1655 1660 Ser Asp Leu Ser Glu Ala Asp Leu Val Ala Val Lys Asp Ala Phe Gly 1665 1670 1675 1680 Phe Asp Glu Pro Gln Leu Leu Lys Tyr Tyr Thr Met Leu Gly Met Cys 1685 1690 1695 Lys Trp Pro Val Val Val Cys Gly Asn Tyr Phe Ala Phe Lys Gln Ser 1700 1705 1710 Asn Asn Asn Cys Tyr Ile Asn Val Ala Cys Leu Met Leu Gln His Leu 1715 1720 1725 Ser Leu Lys Phe Pro Lys Trp Gln Trp Gln Glu Ala Trp Asn Glu Phe 1730 1735 1740 Arg Ser Gly Lys Pro Leu Arg Phe Val Ser Leu Val Leu Ala Lys Gly 1745 1750 1755 1760 Ser Phe Lys Phe Asn Glu Pro Ser Asp Ser Ile Asp Phe Met Arg Val 1765 1770 1775 Val Leu Arg Glu Ala Asp Leu Ser Gly Ala Thr Cys Asn Leu Glu Phe 1780 1785 1790 Val Cys Lys Cys Gly Val Lys Gln Glu Gln Arg Lys Gly Val Asp Ala 1795 1800 1805 Val Met His Phe Gly Thr Leu Asp Lys Gly Asp Leu Val Arg Gly Tyr 1810 1815 1820 Asn Ile Ala Cys Thr Cys Gly Ser Lys Leu Val His Cys Thr Gln Phe 1825 1830 1835 1840 Asn Val Pro Phe Leu Ile Cys Ser Asn Thr Pro Glu Gly Arg Lys Leu 1845 1850 1855 Pro Asp Asp Val Val Ala Ala Asn Ile Phe Thr Gly Gly Ser Val Gly 1860 1865 1870 His Tyr Thr His Val Lys Cys Lys Pro Lys Tyr Gln Leu Tyr Asp Ala 1875 1880 1885 Cys Asn Val Asn Lys Val Ser Glu Ala Lys Gly Asn Phe Thr Asp Cys 1890 1895 1900 Leu Tyr Leu Lys Asn Leu Lys Gln Thr Phe Ser Ser Val Leu Thr Thr 1905 1910 1915 1920 Phe Tyr Leu Asp Asp Val Lys Cys Val Glu Tyr Lys Pro Asp Leu Ser 1925 1930 1935 Gln Tyr Tyr Cys Glu Ser Gly Lys Tyr Tyr Thr Lys Pro Ile Ile Lys 1940 1945 1950 Ala Gln Phe Arg Thr Phe Glu Lys Val Asp Gly Val Tyr Thr Asn Phe 1955 1960 1965 Lys Leu Val Gly His Ser Ile Ala Glu Lys Leu Asn Ala Lys Leu Gly 1970 1975 1980 Phe Asp Cys Asn Ser Pro Phe Val Glu Tyr Lys Ile Thr Glu Trp Pro 1985 1990 1995 2000 Thr Ala Thr Gly Asp Val Val Leu Ala Ser Asp Asp Leu Tyr Val Ser 2005 2010 2015 Arg Tyr Leu Ser Gly Cys Ile Thr Phe Gly Lys Pro Val Val Trp Leu 2020 2025 2030 Gly His Glu Glu Ala Ser Leu Lys Ser Leu Thr Tyr Phe Asn Arg Pro 2035 2040 2045 Ser Val Val Cys Glu Asn Lys Phe Asn Val Leu Pro Val Asp Val Ser 2050 2055 2060 Glu Pro Thr Asp Lys Gly Pro Val Pro Ala Ala Val Leu Val Thr Gly 2065 2070 2075 2080 Val Pro Gly Ala Asp Ala Ser Ala Gly Ala Gly Ile Ala Lys Glu Gln 2085 2090 2095 Lys Ala Cys Ala Ser Ala Ser Val Glu Asp Gln Val Val Thr Glu Val 2100 2105 2110 Arg Gln Glu Pro Ser Val Ser Ala Ala Asp Val Lys Glu Val Lys Leu 2115 2120 2125 Asn Gly Val Lys Lys Pro Val Lys Val Glu Gly Ser Val Val Val Asn 2130 2135 2140 Asp Pro Thr Ser Glu Thr Lys Val Val Lys Ser Leu Ser Ile Val Asp 2145 2150 2155 2160 Val Tyr Asp Met Phe Leu Thr Gly Cys Lys Tyr Val Val Trp Thr Ala 2165 2170 2175 Asn Glu Leu Ser Arg Leu Val Asn Ser Pro Thr Val Arg Glu Tyr Val 2180 2185 2190 Lys Trp Gly Met Gly Lys Ile Val Thr Pro Ala Lys Leu Leu Leu Leu 2195 2200 2205 Arg Asp Glu Lys Gln Glu Phe Val Ala Pro Lys Val Val Lys Ala Lys 2210 2215 2220 Ala Ile Ala Cys Tyr Cys Ala Val Lys Trp Phe Leu Leu Tyr Cys Phe 2225 2230 2235 2240 Ser Trp Ile Lys Phe Asn Thr Asp Asn Lys Val Ile Tyr Thr Thr Glu 2245 2250 2255 Val Ala Ser Lys Leu Thr Phe Lys Leu Cys Cys Leu Ala Phe Lys Asn 2260 2265 2270 Ala Leu Gln Thr Phe Asn Trp Ser Val Val Ser Arg Gly Phe Phe Leu 2275 2280 2285 Val Ala Thr Val Phe Leu Leu Trp Phe Asn Phe Leu Tyr Ala Asn Val 2290 2295 2300 Ile Leu Ser Asp Phe Tyr Leu Pro Asn Ile Gly Pro Leu Pro Thr Phe 2305 2310 2315 2320 Val Gly Gln Ile Val Ala Trp Phe Lys Thr Thr Phe Gly Val Ser Thr 2325 2330 2335 Ile Cys Asp Phe Tyr Gln Val Thr Asp Leu Gly Tyr Arg Ser Ser Phe 2340 2345 2350 Cys Asn Gly Ser Met Val Cys Glu Leu Cys Phe Ser Gly Phe Asp Met 2355 2360 2365 Leu Asp Asn Tyr Asp Ala Ile Asn Val Val Gln His Val Val Asp Arg 2370 2375 2380 Arg Leu Ser Phe Asp Tyr Ile Ser Leu Phe Lys Leu Val Val Glu Leu 2385 2390 2395 2400 Val Ile Gly Tyr Ser Leu Tyr Thr Val Cys Phe Tyr Pro Leu Phe Val 2405 2410 2415 Leu Ile Gly Met Gln Leu Leu Thr Thr Trp Leu Pro Glu Phe Phe Met 2420 2425 2430 Leu Glu Thr Met His Trp Ser Ala Arg Leu Phe Val Phe Val Ala Asn 2435 2440 2445 Met Leu Pro Ala Phe Thr Leu Leu Arg Phe Tyr Ile Val Val Thr Ala 2450 2455 2460 Met Tyr Lys Val Tyr Cys Leu Cys Arg His Val Met Tyr Gly Cys Ser 2465 2470 2475 2480 Lys Pro Gly Cys Leu Phe Cys Tyr Lys Arg Asn Arg Ser Val Arg Val 2485 2490 2495 Lys Cys Ser Thr Val Val Gly Gly Ser Leu Arg Tyr Tyr Asp Val Met 2500 2505 2510 Ala Asn Gly Gly Thr Gly Phe Cys Thr Lys His Gln Trp Asn Cys Leu 2515 2520 2525 Asn Cys Asn Ser Trp Lys Pro Gly Asn Thr Phe Ile Thr His Glu Ala 2530 2535 2540 Ala Ala Asp Leu Ser Lys Glu Leu Lys Arg Pro Val Asn Pro Thr Asp 2545 2550 2555 2560 Ser Ala Tyr Tyr Ser Val Thr Glu Val Lys Gln Val Gly Cys Ser Met 2565 2570 2575 Arg Leu Phe Tyr Glu Arg Asp Gly Gln Arg Val Tyr Asp Asp Val Asn 2580 2585 2590 Ala Ser Leu Phe Val Asp Met Asn Gly Leu Leu His Ser Lys Val Lys 2595 2600 2605 Gly Val Pro Glu Thr His Val Val Val Val Glu Asn Glu Ala Asp Lys 2610 2615 2620 Ala Gly Phe Leu Gly Ala Ala Val Phe Tyr Ala Gln Ser Leu Tyr Arg 2625 2630 2635 2640 Pro Met Leu Met Val Glu Lys Lys Leu Ile Thr Thr Ala Asn Thr Gly 2645 2650 2655 Leu Ser Val Ser Arg Thr Met Phe Asp Leu Tyr Val Asp Ser Leu Leu 2660 2665 2670 Asn Val Leu Asp Val Asp Arg Lys Ser Leu Thr Ser Phe Val Asn Ala 2675 2680 2685 Ala His Asn Ser Leu Lys Glu Gly Val Gln Leu Glu Gln Val Met Asp 2690 2695 2700 Thr Phe Ile Gly Cys Ala Arg Arg Lys Cys Ala Ile Asp Ser Asp Val 2705 2710 2715 2720 Glu Thr Lys Ser Ile Thr Lys Ser Val Met Ser Ala Val Asn Ala Gly 2725 2730 2735 Val Asp Phe Thr Asp Glu Ser Cys Asn Asn Leu Val Pro Thr Tyr Val 2740 2745 2750 Lys Ser Asp Thr Ile Val Ala Ala Asp Leu Gly Val Leu Ile Gln Asn 2755 2760 2765 Asn Ala Lys His Val Gln Ala Asn Val Ala Lys Ala Ala Asn Val Ala 2770 2775 2780 Cys Ile Trp Ser Val Asp Ala Phe Asn Gln Leu Ser Ala Asp Leu Gln 2785 2790 2795 2800 His Arg Leu Arg Lys Ala Cys Ser Lys Thr Gly Leu Lys Ile Lys Leu 2805 2810 2815 Thr Tyr Asn Lys Gln Glu Ala Asn Val Pro Ile Leu Thr Thr Pro Phe 2820 2825 2830 Ser Leu Lys Gly Gly Ala Val Phe Ser Arg Met Leu Gln Trp Leu Phe 2835 2840 2845 Val Ala Asn Leu Ile Cys Phe Ile Val Leu Trp Ala Leu Met Pro Thr 2850 2855 2860 Tyr Ala Val His Lys Ser Asp Met Gln Leu Pro Leu Tyr Ala Ser Phe 2865 2870 2875 2880 Lys Val Ile Asp Asn Gly Val Leu Arg Asp Val Ser Val Thr Asp Ala 2885 2890 2895 Cys Phe Ala Asn Lys Phe Asn Gln Phe Asp Gln Trp Tyr Glu Ser Thr 2900 2905 2910 Phe Gly Leu Ala Tyr Tyr Arg Asn Ser Lys Ala Cys Pro Val Val Val 2915 2920 2925 Ala Val Ile Asp Gln Asp Ile Gly His Thr Leu Phe Asn Val Pro Thr 2930 2935 2940 Thr Val Leu Arg Tyr Gly Phe His Val Leu His Phe Ile Thr His Ala 2945 2950 2955 2960 Phe Ala Thr Asp Ser Val Gln Cys Tyr Thr Pro His Met Gln Ile Pro 2965 2970 2975 Tyr Asp Asn Phe Tyr Ala Ser Gly Cys Val Leu Ser Ser Leu Cys Thr 2980 2985 2990 Met Leu Ala His Ala Asp Gly Thr Pro His Pro Tyr Cys Tyr Thr Gly 2995 3000 3005 Gly Val Met His Asn Ala Ser Leu Tyr Ser Ser Leu Ala Pro His Val 3010 3015 3020 Arg Tyr Asn Leu Ala Ser Ser Asn Gly Tyr Ile Arg Phe Pro Glu Val 3025 3030 3035 3040 Val Ser Glu Gly Ile Val Arg Val Val Arg Thr Arg Ser Met Thr Tyr 3045 3050 3055 Cys Arg Val Gly Leu Cys Glu Glu Ala Glu Glu Gly Ile Cys Phe Asn 3060 3065 3070 Phe Asn Arg Ser Trp Val Leu Asn Asn Pro Tyr Tyr Arg Ala Met Pro 3075 3080 3085 Gly Thr Phe Cys Gly Arg Asn Ala Phe Asp Leu Ile His Gln Val Leu 3090 3095 3100 Gly Gly Leu Val Arg Pro Ile Asp Phe Phe Ala Leu Thr Ala Ser Ser 3105 3110 3115 3120 Val Ala Gly Ala Ile Leu Ala Ile Ile Val Val Leu Ala Phe Tyr Tyr 3125 3130 3135 Leu Ile Lys Leu Lys Arg Ala Phe Gly Asp Tyr Thr Ser Val Val Val 3140 3145 3150 Ile Asn Val Ile Val Trp Cys Ile Asn Phe Leu Met Leu Phe Val Phe 3155 3160 3165 Gln Val Tyr Pro Thr Leu Ser Cys Leu Tyr Ala Cys Phe Tyr Phe Tyr 3170 3175 3180 Thr Thr Leu Tyr Phe Pro Ser Glu Ile Ser Val Val Met His Leu Gln 3185 3190 3195 3200 Trp Leu Val Met Tyr Gly Ala Ile Met Pro Leu Trp Phe Cys Ile Ile 3205 3210 3215 Tyr Val Ala Val Val Val Ser Asn His Ala Leu Trp Leu Phe Ser Tyr 3220 3225 3230 Cys Arg Lys Ile Gly Thr Glu Val Arg Ser Asp Gly Thr Phe Glu Glu 3235 3240 3245 Met Ala Leu Thr Thr Phe Met Ile Thr Lys Glu Ser Tyr Cys Lys Leu 3250 3255 3260 Lys Asn Ser Val Ser Asp Val Ala Phe Asn Arg Tyr Leu Ser Leu Tyr 3265 3270 3275 3280 Asn Lys Tyr Arg Tyr Phe Ser Gly Lys Met Asp Thr Ala Ala Tyr Arg 3285 3290 3295 Glu Ala Ala Cys Ser Gln Leu Ala Lys Ala Met Glu Thr Phe Asn His 3300 3305 3310 Asn Asn Gly Asn Asp Val Leu Tyr Gln Pro Pro Thr Ala Ser Val Thr 3315 3320 3325 Thr Ser Phe Leu Gln Ser Gly Ile Val Lys Met Val Ser Pro Thr Ser 3330 3335 3340 Lys Val Glu Pro Cys Ile Val Ser Val Thr Tyr Gly Asn Met Thr Leu 3345 3350 3355 3360 Asn Gly Leu Trp Leu Asp Asp Lys Val Tyr Cys Pro Arg His Val Ile 3365 3370 3375 Cys Ser Ser Ala Asp Met Thr Asp Pro Asp Tyr Pro Asn Leu Leu Cys 3380 3385 3390 Arg Val Thr Ser Ser Asp Phe Cys Val Met Ser Gly Arg Met Ser Leu 3395 3400 3405 Thr Val Met Ser Tyr Gln Met Gln Gly Cys Gln Leu Val Leu Thr Val 3410 3415 3420 Thr Leu Gln Asn Pro Asn Thr Pro Lys Tyr Ser Phe Gly Val Val Lys 3425 3430 3435 3440 Pro Gly Glu Thr Phe Thr Val Leu Ala Ala Tyr Asn Gly Arg Pro Gln 3445 3450 3455 Gly Ala Phe His Val Thr Leu Arg Ser Ser His Thr Ile Lys Gly Ser 3460 3465 3470 Phe Leu Cys Gly Ser Cys Gly Ser Val Gly Tyr Val Leu Thr Gly Asp 3475 3480 3485 Ser Val Arg Phe Val Tyr Met His Gln Leu Glu Leu Ser Thr Gly Cys 3490 3495 3500 His Thr Gly Thr Asp Phe Ser Gly Asn Phe Tyr Gly Pro Tyr Arg Asp 3505 3510 3515 3520 Ala Gln Val Val Gln Leu Pro Val Gln Asp Tyr Thr Gln Thr Val Asn 3525 3530 3535 Val Val Ala Trp Leu Tyr Ala Ala Ile Phe Asn Arg Cys Asn Trp Phe 3540 3545 3550 Val Gln Ser Asp Ser Cys Ser Leu Glu Glu Phe Asn Val Trp Ala Met 3555 3560 3565 Thr Asn Gly Phe Ser Ser Ile Lys Ala Asp Leu Val Leu Asp Ala Leu 3570 3575 3580 Ala Ser Met Thr Gly Val Thr Val Glu Gln Val Leu Ala Ala Ile Lys 3585 3590 3595 3600 Arg Leu His Ser Gly Phe Gln Gly Lys Gln Ile Leu Gly Ser Cys Val 3605 3610 3615 Leu Glu Asp Glu Leu Thr Pro Ser Asp Val Tyr Gln Gln Leu Ala Gly 3620 3625 3630 Val Lys Leu Gln Ser Lys Arg Thr Arg Val Ile Lys Gly Thr Cys Cys 3635 3640 3645 Trp Ile Leu Ala Ser Thr Phe Leu Phe Cys Ser Ile Ile Ser Ala Phe 3650 3655 3660 Val Lys Trp Thr Met Phe Met Tyr Val Thr Thr His Met Leu Gly Val 3665 3670 3675 3680 Thr Leu Cys Ala Leu Cys Phe Val Ser Phe Ala Met Leu Leu Ile Lys 3685 3690 3695 His Lys His Leu Tyr Leu Thr Met Tyr Ile Met Pro Val Leu Cys Thr 3700 3705 3710 Leu Phe Tyr Thr Asn Tyr Leu Val Val Tyr Lys Gln Ser Phe Arg Gly 3715 3720 3725 Leu Ala Tyr Ala Trp Leu Ser His Phe Val Pro Ala Val Asp Tyr Thr 3730 3735 3740 Tyr Met Asp Glu Val Leu Tyr Gly Val Val Leu Leu Val Ala Met Val 3745 3750 3755 3760 Phe Val Thr Met Arg Ser Ile Asn His Asp Val Phe Ser Ile Met Phe 3765 3770 3775 Leu Val Gly Arg Leu Val Ser Leu Val Ser Met Trp Tyr Phe Gly Ala 3780 3785 3790 Asn Leu Glu Glu Glu Val Leu Leu Phe Leu Thr Ser Leu Phe Gly Thr 3795 3800 3805 Tyr Thr Trp Thr Thr Met Leu Ser Leu Ala Thr Ala Lys Val Ile Ala 3810 3815 3820 Lys Trp Leu Ala Val Asn Val Leu Tyr Phe Thr Asp Val Pro Gln Ile 3825 3830 3835 3840 Lys Leu Val Leu Leu Ser Tyr Leu Cys Ile Gly Tyr Val Cys Cys Cys 3845 3850 3855 Tyr Trp Gly Ile Leu Ser Leu Leu Asn Ser Ile Phe Arg Met Pro Leu 3860 3865 3870 Gly Val Tyr Asn Tyr Lys Ile Ser Val Gln Glu Leu Arg Tyr Met Asn 3875 3880 3885 Ala Asn Gly Leu Arg Pro Pro Arg Asn Ser Phe Glu Ala Leu Met Leu 3890 3895 3900 Asn Phe Lys Leu Leu Gly Ile Gly Gly Val Pro Val Ile Glu Val Ser 3905 3910 3915 3920 Gln Ile Gln Ser Arg Leu Thr Asp Val Lys Cys Ala Asn Val Val Leu 3925 3930 3935 Leu Asn Cys Leu Gln His Leu His Ile Ala Ser Asn Ser Lys Leu Trp 3940 3945 3950 Gln Tyr Cys Ser Thr Leu His Asn Glu Ile Leu Ala Thr Ser Asp Leu 3955 3960 3965 Ser Val Ala Phe Asp Lys Leu Ala Gln Leu Leu Val Val Leu Phe Ala 3970 3975 3980 Asn Pro Ala Ala Val Asp Ser Lys Cys Leu Ala Ser Ile Glu Glu Val 3985 3990 3995 4000 Ser Asp Asp Tyr Val Arg Asp Asn Thr Val Leu Gln Ala Leu Gln Ser 4005 4010 4015 Glu Phe Val Asn Met Ala Ser Phe Val Glu Tyr Glu Leu Ala Lys Lys 4020 4025 4030 Asn Leu Asp Glu Ala Lys Ala Ser Gly Ser Ala Asn Gln Gln Gln Ile 4035 4040 4045 Lys Gln Leu Glu Lys Ala Cys Asn Ile Ala Lys Ser Ala Tyr Glu Arg 4050 4055 4060 Asp Arg Ala Val Ala Arg Lys Leu Glu Arg Met Ala Asp Leu Ala Leu 4065 4070 4075 4080 Thr Asn Met Tyr Lys Glu Ala Arg Ile Asn Asp Lys Lys Ser Lys Val 4085 4090 4095 Val Ser Ala Leu Gln Thr Met Leu Phe Ser Met Val Arg Lys Leu Asp 4100 4105 4110 Asn Gln Ala Leu Asn Ser Ile Leu Asp Asn Ala Val Lys Gly Cys Val 4115 4120 4125 Pro Leu Asn Ala Ile Pro Ser Leu Thr Ser Asn Thr Leu Thr Ile Ile 4130 4135 4140 Val Pro Asp Lys Gln Val Phe Asp Gln Val Val Asp Asn Val Tyr Val 4145 4150 4155 4160 Thr Tyr Ala Gly Asn Val Trp His Ile Gln Phe Ile Gln Asp Ala Asp 4165 4170 4175 Gly Ala Val Lys Gln Leu Asn Glu Ile Asp Val Asn Ser Thr Trp Pro 4180 4185 4190 Leu Val Ile Ala Ala Asn Arg His Asn Glu Val Ser Thr Val Val Leu 4195 4200 4205 Gln Asn Asn Glu Leu Met Pro Gln Lys Leu Arg Thr Gln Val Val Asn 4210 4215 4220 Ser Gly Ser Asp Met Asn Cys Asn Thr Pro Thr Gln Cys Tyr Tyr Asn 4225 4230 4235 4240 Thr Thr Gly Thr Gly Lys Ile Val Tyr Ala Ile Leu Ser Asp Cys Asp 4245 4250 4255 Gly Leu Lys Tyr Thr Lys Ile Val Lys Glu Asp Gly Asn Cys Val Val 4260 4265 4270 Leu Glu Leu Asp Pro Pro Cys Lys Phe Ser Val Gln Asp Val Lys Gly 4275 4280 4285 Leu Lys Ile Lys Tyr Leu Tyr Phe Val Lys Gly Cys Asn Thr Leu Ala 4290 4295 4300 Arg Gly Trp Val Val Gly Thr Leu Ser Ser Thr Val Arg Leu Gln Ala 4305 4310 4315 4320 Gly Thr Ala Thr Glu Tyr Ala Ser Asn Ser Ala Ile Leu Ser Leu Cys 4325 4330 4335 Ala Phe Ser Val Asp Pro Lys Lys Thr Tyr Leu Asp Tyr Ile Lys Gln 4340 4345 4350 Gly Gly Val Pro Val Thr Asn Cys Val Lys Met Leu Cys Asp His Ala 4355 4360 4365 Gly Thr Gly Met Ala Ile Thr Ile Lys Pro Glu Ala Thr Thr Asn Gln 4370 4375 4380 Asp Ser Tyr Gly Gly Ala Ser Val Cys Ile Tyr Cys Arg Ser Arg Val 4385 4390 4395 4400 Glu His Pro Asp Val Asp Gly Leu Cys Lys Leu Arg Gly Lys Phe Val 4405 4410 4415 Gln Val Pro Leu Gly Ile Lys Asp Pro Val Ser Tyr Val Leu Thr His 4420 4425 4430 Asp Val Cys Gln Val Cys Gly Phe Trp Arg Asp Gly Ser Cys Ser Cys 4435 4440 4445 Val Gly Thr Gly Ser Gln Phe Gln Ser Lys Asp Thr Asn Phe Leu Asn 4450 4455 4460 Gly Phe Gly Val Gln Val 4465 4470 <210> 32 <211> 2714 <212> PRT <213> Artificial Sequence <220> <223> Synthetic_Replicative_Polyprotein1ab <400> 32 Arg Ile Arg Gly Thr Ser Val Asn Ala Arg Leu Val Pro Cys Ala Ser 1 5 10 15 Gly Leu Asp Thr Asp Val Gln Leu Arg Ala Phe Asp Ile Cys Asn Ala 20 25 30 Asn Arg Ala Gly Ile Gly Leu Tyr Tyr Lys Val Asn Cys Cys Arg Phe 35 40 45 Gln Arg Val Asp Glu Asp Gly Asn Lys Leu Asp Lys Phe Phe Val Val 50 55 60 Lys Arg Thr Asn Leu Glu Val Tyr Asn Lys Glu Lys Glu Cys Tyr Glu 65 70 75 80 Leu Thr Lys Glu Cys Gly Val Val Ala Glu His Glu Phe Phe Thr Phe 85 90 95 Asp Val Glu Gly Ser Arg Val Pro His Ile Val Arg Lys Asp Leu Ser 100 105 110 Lys Phe Thr Met Leu Asp Leu Cys Tyr Ala Leu Arg His Phe Asp Arg 115 120 125 Asn Asp Cys Ser Thr Leu Lys Glu Ile Leu Leu Thr Tyr Ala Glu Cys 130 135 140 Glu Glu Ser Tyr Phe Gln Lys Lys Asp Trp Tyr Asp Phe Val Glu Asn 145 150 155 160 Pro Asp Ile Ile Asn Val Tyr Lys Lys Leu Gly Pro Ile Phe Asn Arg 165 170 175 Ala Leu Leu Asn Thr Ala Lys Phe Ala Asp Ala Leu Val Glu Ala Gly 180 185 190 Leu Val Gly Val Leu Thr Leu Asp Asn Gln Asp Leu Tyr Gly Gln Trp 195 200 205 Tyr Asp Phe Gly Asp Phe Val Lys Thr Val Pro Gly Cys Gly Val Ala 210 215 220 Val Ala Asp Ser Tyr Tyr Ser Tyr Met Met Pro Met Leu Thr Met Cys 225 230 235 240 His Ala Leu Asp Ser Glu Leu Phe Val Asn Gly Thr Tyr Arg Glu Phe 245 250 255 Asp Leu Val Gln Tyr Asp Phe Thr Asp Phe Lys Leu Glu Leu Phe Thr 260 265 270 Lys Tyr Phe Lys His Trp Ser Met Thr Tyr His Pro Asn Thr Cys Glu 275 280 285 Cys Glu Asp Asp Arg Cys Ile Ile His Cys Ala Asn Phe Asn Ile Leu 290 295 300 Phe Ser Met Val Leu Pro Lys Thr Cys Phe Gly Pro Leu Val Arg Gln 305 310 315 320 Ile Phe Val Asp Gly Val Pro Phe Val Val Ser Ile Gly Tyr His Tyr 325 330 335 Lys Glu Leu Gly Val Val Met Asn Met Asp Val Asp Thr His Arg Tyr 340 345 350 Arg Leu Ser Leu Lys Asp Leu Leu Leu Tyr Ala Ala Asp Pro Ala Leu 355 360 365 His Val Ala Ser Ala Ser Ala Leu Leu Asp Leu Arg Thr Cys Cys Phe 370 375 380 Ser Val Ala Ala Ile Thr Ser Gly Val Lys Phe Gln Thr Val Lys Pro 385 390 395 400 Gly Asn Phe Asn Gln Asp Phe Tyr Glu Phe Ile Leu Ser Lys Gly Leu 405 410 415 Leu Lys Glu Gly Ser Ser Val Asp Leu Lys His Phe Phe Phe Thr Gln 420 425 430 Asp Gly Asn Ala Ala Ile Thr Asp Tyr Asn Tyr Tyr Lys Tyr Asn Leu 435 440 445 Pro Thr Met Val Asp Ile Lys Gln Leu Leu Phe Val Leu Glu Val Val 450 455 460 Asn Lys Tyr Phe Glu Ile Tyr Glu Gly Gly Cys Ile Pro Ala Thr Gln 465 470 475 480 Val Ile Val Asn Asn Tyr Asp Lys Ser Ala Gly Tyr Pro Phe Asn Lys 485 490 495 Phe Gly Lys Ala Arg Leu Tyr Tyr Glu Ala Leu Ser Phe Glu Glu Gln 500 505 510 Asp Glu Ile Tyr Ala Tyr Thr Lys Arg Asn Val Leu Pro Thr Leu Thr 515 520 525 Gln Met Asn Leu Lys Tyr Ala Ile Ser Ala Lys Asn Arg Ala Arg Thr 530 535 540 Val Ala Gly Val Ser Ile Leu Ser Thr Met Thr Gly Arg Met Phe His 545 550 555 560 Gln Lys Cys Leu Lys Ser Ile Ala Ala Thr Arg Gly Val Pro Val Val 565 570 575 Ile Gly Thr Thr Lys Phe Tyr Gly Gly Trp Asp Asp Met Leu Arg Arg 580 585 590 Leu Ile Lys Asp Val Asp Ser Pro Val Leu Met Gly Trp Asp Tyr Pro 595 600 605 Lys Cys Asp Arg Ala Met Pro Asn Ile Leu Arg Ile Val Ser Ser Leu 610 615 620 Val Leu Ala Arg Lys His Asp Ser Cys Cys Ser His Thr Asp Arg Phe 625 630 635 640 Tyr Arg Leu Ala Asn Glu Cys Ala Gln Val Leu Ser Glu Ile Val Met 645 650 655 Cys Gly Gly Cys Tyr Tyr Val Lys Pro Gly Gly Thr Ser Ser Gly Asp 660 665 670 Ala Thr Thr Ala Phe Ala Asn Ser Val Phe Asn Ile Cys Gln Ala Val 675 680 685 Ser Ala Asn Val Cys Ser Leu Met Ala Cys Asn Gly His Lys Ile Glu 690 695 700 Asp Leu Ser Ile Arg Glu Leu Gln Lys Arg Leu Tyr Ser Asn Val Tyr 705 710 715 720 Arg Ala Asp His Val Asp Pro Ala Phe Val Ser Glu Tyr Tyr Glu Phe 725 730 735 Leu Asn Lys His Phe Ser Met Met Ile Leu Ser Asp Asp Gly Val Val 740 745 750 Cys Tyr Asn Ser Glu Phe Ala Ser Lys Gly Tyr Ile Ala Asn Ile Ser 755 760 765 Ala Phe Gln Gln Val Leu Tyr Tyr Gln Asn Asn Val Phe Met Ser Glu 770 775 780 Ala Lys Cys Trp Val Glu Thr Asp Ile Glu Lys Gly Pro His Glu Phe 785 790 795 800 Cys Ser Gln His Thr Met Leu Val Lys Met Asp Gly Asp Glu Val Tyr 805 810 815 Leu Pro Tyr Pro Asp Pro Ser Arg Ile Leu Gly Ala Gly Cys Phe Val 820 825 830 Asp Asp Leu Leu Lys Thr Asp Ser Val Leu Leu Ile Glu Arg Phe Val 835 840 845 Ser Leu Ala Ile Asp Ala Tyr Pro Leu Val Tyr His Glu Asn Pro Glu 850 855 860 Tyr Gln Asn Val Phe Arg Val Tyr Leu Glu Tyr Ile Lys Lys Leu Tyr 865 870 875 880 Asn Asp Leu Gly Asn Gln Ile Leu Asp Ser Tyr Ser Val Ile Leu Ser 885 890 895 Thr Cys Asp Gly Gln Lys Phe Thr Asp Glu Thr Phe Tyr Lys Asn Met 900 905 910 Tyr Leu Arg Ser Ala Val Leu Gln Ser Val Gly Ala Cys Val Val Cys 915 920 925 Ser Ser Gln Thr Ser Leu Arg Cys Gly Ser Cys Ile Arg Lys Pro Leu 930 935 940 Leu Cys Cys Lys Cys Ala Tyr Asp His Val Met Ser Thr Asp His Lys 945 950 955 960 Tyr Val Leu Ser Val Ser Pro Tyr Val Cys Asn Ser Pro Gly Cys Asp 965 970 975 Val Asn Asp Val Thr Lys Leu Tyr Leu Gly Gly Met Ser Tyr Tyr Cys 980 985 990 Glu Asp His Lys Pro Gln Tyr Ser Phe Lys Leu Val Met Asn Gly Met 995 1000 1005 Val Phe Gly Leu Tyr Lys Gln Ser Cys Thr Gly Ser Pro Tyr Ile Glu 1010 1015 1020 Asp Phe Asn Lys Ile Ala Ser Cys Lys Trp Thr Glu Val Asp Asp Tyr 1025 1030 1035 1040 Val Leu Ala Asn Glu Cys Thr Glu Arg Leu Lys Leu Phe Ala Ala Glu 1045 1050 1055 Thr Gln Lys Ala Thr Glu Glu Ala Phe Lys Gln Cys Tyr Ala Ser Ala 1060 1065 1070 Thr Ile Arg Glu Ile Val Ser Asp Arg Glu Leu Ile Leu Ser Trp Glu 1075 1080 1085 Ile Gly Lys Val Arg Pro Pro Leu Asn Lys Asn Tyr Val Phe Thr Gly 1090 1095 1100 Tyr His Phe Thr Asn Asn Gly Lys Thr Val Leu Gly Glu Tyr Val Phe 1105 1110 1115 1120 Asp Lys Ser Glu Leu Thr Asn Gly Val Tyr Tyr Arg Ala Thr Thr Thr 1125 1130 1135 Tyr Lys Leu Ser Val Gly Asp Val Phe Ile Leu Thr Ser His Ala Val 1140 1145 1150 Ser Ser Leu Ser Ala Pro Thr Leu Val Pro Gln Glu Asn Tyr Thr Ser 1155 1160 1165 Ile Arg Phe Ala Ser Val Tyr Ser Val Pro Glu Thr Phe Gln Asn Asn 1170 1175 1180 Val Pro Asn Tyr Gln His Ile Gly Met Lys Arg Tyr Cys Thr Val Gln 1185 1190 1195 1200 Gly Pro Pro Gly Thr Gly Lys Ser His Leu Ala Ile Gly Leu Ala Val 1205 1210 1215 Tyr Tyr Cys Thr Ala Arg Val Val Tyr Thr Ala Ala Ser His Ala Ala 1220 1225 1230 Val Asp Ala Leu Cys Glu Lys Ala His Lys Phe Leu Asn Ile Asn Asp 1235 1240 1245 Cys Thr Arg Ile Val Pro Ala Lys Val Arg Val Asp Cys Tyr Asp Lys 1250 1255 1260 Phe Lys Val Asn Asp Thr Thr Arg Lys Tyr Val Phe Thr Thr Ile Asn 1265 1270 1275 1280 Ala Leu Pro Glu Leu Val Thr Asp Ile Ile Val Val Asp Glu Val Ser 1285 1290 1295 Met Leu Thr Asn Tyr Glu Leu Ser Val Ile Asn Ser Arg Val Arg Ala 1300 1305 1310 Lys His Tyr Val Tyr Ile Gly Asp Pro Ala Gln Leu Pro Ala Pro Arg 1315 1320 1325 Val Leu Leu Asn Lys Gly Thr Leu Glu Pro Arg Tyr Phe Asn Ser Val 1330 1335 1340 Thr Lys Leu Met Cys Cys Leu Gly Pro Asp Ile Phe Leu Gly Thr Cys 1345 1350 1355 1360 Tyr Arg Cys Pro Lys Glu Ile Val Asp Thr Val Ser Ala Leu Val Tyr 1365 1370 1375 Asn Asn Lys Leu Lys Ala Lys Asn Asp Asn Ser Ser Met Cys Phe Lys 1380 1385 1390 Val Tyr Tyr Lys Gly Gln Thr Thr His Glu Ser Ser Ser Ala Val Asn 1395 1400 1405 Met Gln Gln Ile His Leu Ile Ser Lys Phe Leu Lys Ala Asn Pro Ser 1410 1415 1420 Trp Ser Asn Ala Val Phe Ile Ser Pro Tyr Asn Ser Gln Asn Tyr Val 1425 1430 1435 1440 Ala Lys Arg Val Leu Gly Leu Gln Thr Gln Thr Val Asp Ser Ala Gln 1445 1450 1455 Gly Ser Glu Tyr Asp Phe Val Ile Tyr Ser Gln Thr Ala Glu Thr Ala 1460 1465 1470 His Ser Val Asn Val Asn Arg Phe Asn Val Ala Ile Thr Arg Ala Lys 1475 1480 1485 Lys Gly Ile Leu Cys Val Met Ser Ser Met Gln Leu Phe Glu Ser Leu 1490 1495 1500 Asn Phe Thr Thr Leu Thr Leu Asp Lys Ile Asn Asn Pro Arg Leu Gln 1505 1510 1515 1520 Cys Thr Thr Asn Leu Phe Lys Asp Cys Ser Arg Ser Tyr Val Gly Tyr 1525 1530 1535 His Pro Ala His Ala Pro Ser Phe Leu Ala Val Asp Asp Lys Tyr Lys 1540 1545 1550 Val Gly Gly Asp Leu Ala Val Cys Leu Asn Val Ala Asp Ser Ala Val 1555 1560 1565 Thr Tyr Ser Arg Leu Ile Ser Leu Met Gly Phe Lys Leu Asp Leu Thr 1570 1575 1580 Leu Asp Gly Tyr Cys Lys Leu Phe Ile Thr Arg Asp Glu Ala Ile Lys 1585 1590 1595 1600 Arg Val Arg Ala Trp Val Gly Phe Asp Ala Glu Gly Ala His Ala Ile 1605 1610 1615 Arg Asp Ser Ile Gly Thr Asn Phe Pro Leu Gln Leu Gly Phe Ser Thr 1620 1625 1630 Gly Ile Asp Phe Val Val Glu Ala Thr Gly Met Phe Ala Glu Arg Asp 1635 1640 1645 Gly Tyr Val Phe Lys Lys Ala Ala Ala Arg Ala Pro Pro Gly Glu Gln 1650 1655 1660 Phe Lys His Leu Ile Pro Leu Met Ser Arg Gly Gln Lys Trp Asp Val 1665 1670 1675 1680 Val Arg Ile Arg Ile Val Gln Met Leu Ser Asp His Leu Val Asp Leu 1685 1690 1695 Ala Asp Ser Val Val Leu Val Thr Trp Ala Ala Ser Phe Glu Leu Thr 1700 1705 1710 Cys Leu Arg Tyr Phe Ala Lys Val Gly Arg Glu Val Val Cys Ser Val 1715 1720 1725 Cys Thr Lys Arg Ala Thr Cys Phe Asn Ser Arg Thr Gly Tyr Tyr Gly 1730 1735 1740 Cys Trp Arg His Ser Tyr Ser Cys Asp Tyr Leu Tyr Asn Pro Leu Ile 1745 1750 1755 1760 Val Asp Ile Gln Gln Trp Gly Tyr Thr Gly Ser Leu Thr Ser Asn His 1765 1770 1775 Asp Pro Ile Cys Ser Val His Lys Gly Ala His Val Ala Ser Ser Asp 1780 1785 1790 Ala Ile Met Thr Arg Cys Leu Ala Val His Asp Cys Phe Cys Lys Ser 1795 1800 1805 Val Asn Trp Asn Leu Glu Tyr Pro Ile Ile Ser Asn Glu Val Ser Val 1810 1815 1820 Asn Thr Ser Cys Arg Leu Leu Gln Arg Val Met Phe Arg Ala Ala Met 1825 1830 1835 1840 Leu Cys Asn Arg Tyr Asp Val Cys Tyr Asp Ile Gly Asn Pro Lys Gly 1845 1850 1855 Leu Ala Cys Val Lys Gly Tyr Asp Phe Lys Phe Tyr Asp Ala Ser Pro 1860 1865 1870 Val Val Lys Ser Val Lys Gln Phe Val Tyr Lys Tyr Glu Ala His Lys 1875 1880 1885 Asp Gln Phe Leu Asp Gly Leu Cys Met Phe Trp Asn Cys Asn Val Asp 1890 1895 1900 Lys Tyr Pro Ala Asn Ala Val Val Cys Arg Phe Asp Thr Arg Val Leu 1905 1910 1915 1920 Asn Lys Leu Asn Leu Pro Gly Cys Asn Gly Gly Ser Leu Tyr Val Asn 1925 1930 1935 Lys His Ala Phe His Thr Ser Pro Phe Thr Arg Ala Ala Phe Glu Asn 1940 1945 1950 Leu Lys Pro Met Pro Phe Phe Tyr Tyr Ser Asp Thr Pro Cys Val Tyr 1955 1960 1965 Met Glu Gly Met Glu Ser Lys Gln Val Asp Tyr Val Pro Leu Arg Ser 1970 1975 1980 Ala Thr Cys Ile Thr Arg Cys Asn Leu Gly Gly Ala Val Cys Leu Lys 1985 1990 1995 2000 His Ala Glu Glu Tyr Arg Glu Tyr Leu Glu Ser Tyr Asn Thr Ala Thr 2005 2010 2015 Thr Ala Gly Phe Thr Phe Trp Val Tyr Lys Thr Phe Asp Phe Tyr Asn 2020 2025 2030 Leu Trp Asn Thr Phe Thr Arg Leu Gln Ser Leu Glu Asn Val Val Tyr 2035 2040 2045 Asn Leu Val Asn Ala Gly His Phe Asp Gly Arg Ala Gly Glu Leu Pro 2050 2055 2060 Cys Ala Val Ile Gly Glu Lys Val Ile Ala Lys Ile Gln Asn Glu Asp 2065 2070 2075 2080 Val Val Val Phe Lys Asn Asn Thr Pro Phe Pro Thr Asn Val Ala Val 2085 2090 2095 Glu Leu Phe Ala Lys Arg Ser Ile Arg Pro His Pro Glu Leu Lys Leu 2100 2105 2110 Phe Arg Asn Leu Asn Ile Asp Val Cys Trp Ser His Val Leu Trp Asp 2115 2120 2125 Tyr Ala Lys Asp Ser Val Phe Cys Ser Ser Thr Tyr Lys Val Cys Lys 2130 2135 2140 Tyr Thr Asp Leu Gln Cys Ile Glu Ser Leu Asn Val Leu Phe Asp Gly 2145 2150 2155 2160 Arg Asp Asn Gly Ala Leu Glu Ala Phe Lys Lys Cys Arg Asn Gly Val 2165 2170 2175 Tyr Ile Asn Thr Thr Lys Ile Lys Ser Leu Ser Met Ile Lys Gly Pro 2180 2185 2190 Gln Arg Ala Asp Leu Asn Gly Val Val Val Glu Lys Val Gly Asp Ser 2195 2200 2205 Asp Val Glu Phe Trp Phe Ala Val Arg Lys Asp Gly Asp Asp Val Ile 2210 2215 2220 Phe Ser Arg Thr Gly Ser Leu Glu Pro Ser His Tyr Arg Ser Pro Gln 2225 2230 2235 2240 Gly Asn Pro Gly Gly Asn Arg Val Gly Asp Leu Ser Gly Asn Glu Ala 2245 2250 2255 Leu Ala Arg Gly Thr Ile Phe Thr Gln Ser Arg Leu Leu Ser Ser Phe 2260 2265 2270 Thr Pro Arg Ser Glu Met Glu Lys Asp Phe Met Asp Leu Asp Asp Asp 2275 2280 2285 Val Phe Ile Ala Lys Tyr Ser Leu Gln Asp Tyr Ala Phe Glu His Val 2290 2295 2300 Val Tyr Gly Ser Phe Asn Gln Lys Ile Ile Gly Gly Leu His Leu Leu 2305 2310 2315 2320 Ile Gly Leu Ala Arg Arg Gln Gln Lys Ser Asn Leu Val Ile Gln Glu 2325 2330 2335 Phe Val Thr Tyr Asp Ser Ser Ile His Ser Tyr Phe Ile Thr Asp Glu 2340 2345 2350 Asn Ser Gly Ser Ser Lys Ser Val Cys Thr Val Ile Asp Leu Leu Leu 2355 2360 2365 Asp Asp Phe Val Asp Ile Val Lys Ser Leu Asn Leu Lys Cys Val Ser 2370 2375 2380 Lys Val Val Asn Val Asn Val Asp Phe Lys Asp Phe Gln Phe Met Leu 2385 2390 2395 2400 Trp Cys Asn Glu Glu Lys Val Met Thr Phe Tyr Pro Arg Leu Gln Ala 2405 2410 2415 Ala Ala Asp Trp Lys Pro Gly Tyr Val Met Pro Val Leu Tyr Lys Tyr 2420 2425 2430 Leu Glu Ser Pro Leu Glu Arg Val Asn Leu Trp Asn Tyr Gly Lys Pro 2435 2440 2445 Ile Thr Leu Pro Thr Gly Cys Met Met Asn Val Ala Lys Tyr Thr Gln 2450 2455 2460 Leu Cys Gln Tyr Leu Ser Thr Thr Thr Leu Ala Val Pro Ala Asn Met 2465 2470 2475 2480 Arg Val Leu His Leu Gly Ala Gly Ser Asp Lys Gly Val Ala Pro Gly 2485 2490 2495 Ser Ala Val Leu Arg Gln Trp Leu Pro Ala Gly Ser Ile Leu Val Asp 2500 2505 2510 Asn Asp Val Asn Pro Phe Val Ser Asp Ser Val Ala Ser Tyr Tyr Gly 2515 2520 2525 Asn Cys Ile Thr Leu Pro Phe Asp Cys Gln Trp Asp Leu Ile Ile Ser 2530 2535 2540 Asp Met Tyr Asp Pro Leu Thr Lys Asn Ile Gly Glu Tyr Asn Val Ser 2545 2550 2555 2560 Lys Asp Gly Phe Phe Thr Tyr Leu Cys His Leu Ile Arg Asp Lys Leu 2565 2570 2575 Ala Leu Gly Gly Ser Val Ala Ile Lys Ile Thr Glu Phe Ser Trp Asn 2580 2585 2590 Ala Glu Leu Tyr Ser Leu Met Gly Lys Phe Ala Phe Trp Thr Ile Phe 2595 2600 2605 Cys Thr Asn Val Asn Ala Ser Ser Ser Glu Gly Phe Leu Ile Gly Ile 2610 2615 2620 Asn Trp Leu Asn Lys Thr Arg Thr Glu Ile Asp Gly Lys Thr Met His 2625 2630 2635 2640 Ala Asn Tyr Leu Phe Trp Arg Asn Ser Thr Met Trp Asn Gly Gly Ala 2645 2650 2655 Tyr Ser Leu Phe Asp Met Ser Lys Phe Pro Leu Lys Ala Ala Gly Thr 2660 2665 2670 Ala Val Val Ser Leu Lys Pro Asp Gln Ile Asn Asp Leu Val Leu Ser 2675 2680 2685 Leu Ile Glu Lys Gly Lys Leu Leu Val Arg Asp Thr Arg Lys Glu Val 2690 2695 2700 Phe Val Gly Asp Ser Leu Val Asn Val Lys 2705 2710 <210> 33 <211> 29844 <212> DNA <213> Artificial Sequence <220> <223> COVAX191_delta_N_RNA <400> 33 gtataagagt gattggcgtc cgtacgtacc ctctcaactc taaaactctt gtagtttaaa 60 tctaatctaa actttataaa cggcacttcc tgcgtgtcca tgcccgcggg cctggtcttg 120 tcatagtgct gacatttgta gttccttgac tttcgttctc tgccagtgac gtgtccattc 180 ggcgccagca gcccacccat aggttgcata atggcaaaga tgggcaaata cggcctgggc 240 ttcaaatggg ccccagaatt tccatggatg cttccgaacg catcggagaa gttgggtaac 300 cctgagaggt cagaggagga tgggttttgc ccctctgctg cgcaagaacc gaaagttaaa 360 ggaaaaactt tggttaatca cgtgagggtg aattgtagcc ggcttccagc tttggaatgc 420 tgtgttcagt ctgccataat ccgtgatatt tttgtagatg aggatcccca gaaggtggag 480 gcctcaacta tgatggcatt gcagttcggt agtgccgtct tggttaagcc atccaagcgc 540 ttgtctattc aggcatggac taatttgggt gtgcttccca aaacagctgc catggggttg 600 ttcaagcgcg tctgcctgtg taacaccagg gagtgctctt gtgacgccca cgtggccttt 660 caccttttta cggtccaacc cgatggtgta tgcctgggta atggccgttt tataggctgg 720 ttcgttccag tcacagccat accggagtat gcgaagcagt ggttgcaacc ctggtccatc 780 cttcttcgta agggtggtaa caaagggtct gtgacatccg gccacttccg ccgcgctgtt 840 accatgcctg tgtatgactt taatgtagag gatgcttgtg aggaggttca tcttaacccg 900 aagggtaagt actcctgcaa ggcgtatgcc ctgctgaagg gctatcgcgg tgttaagccc 960 atcctgtttg tggaccagta tggttgcgac tatactggat gtctcgccaa gggtcttgag 1020 gactatggcg atctcacctt gagtgagatg aaggagttgt tccctgtgtg gcgtgactcc 1080 ttggatagtg aagtccttgt ggcttggcac gttgatcgag atcctcgggc tgctatgcgt 1140 ctgcagactc ttgctactgt acgttgcatt gattatgtgg gccaaccgac cgaggatgtg 1200 gtggatggag atgtggtagt gcgtgagcct gctcatcttc tcgcagccaa tgccattgtt 1260 aaaagactcc cccgtttggt ggagactatg ctgtatacgg attcgtccgt tacagaattc 1320 tgttataaaa ccaagctgtg tgaatgcggt tttatcacgc agtttggcta tgtggattgt 1380 tgtggtgaca cctgtgattt tcgtgggtgg gttgccggca atatgatgga tggctttcca 1440 tgtccagggt gtaccaaaaa ttatatgccc tgggaattgg aggcccagtc atcaggtgtt 1500 ataccagaag gaggtgttct attcactcag agcactgata cagtgaatcg tgagtccttt 1560 aagctctacg gtcatgctgt tgtgcctttt ggttctgctg tgtattggag cccttgccca 1620 ggtatgtggc ttccagtaat ttggtcgtcg gttaagtcat actctggttt gacttataca 1680 ggagtagttg gttgtaaggc aattgttcaa gagacagacg ctatatgtcg ttctctgtat 1740 atggattatg tccagcacaa gtgtggcaat ctcgagcaga gagctatcct tggattggac 1800 gatgtctatc atagacagtt gcttgtgaat aggggtgact atagtctcct ccttgagaat 1860 gtggatttgt ttgttaagcg gcgcgctgaa tttgcttgca aattcgccac ctgtggagat 1920 ggtcttgtac ccctcctact agatggttta gtgccccgca gttattattt gattaagagt 1980 ggtcaagctt tcacctctat gatggttaat tttagccatg aggtgactga catgtgtatg 2040 gacatggctt tattgttcat gcatgatgtt aaagtggcca ctaagtatgt taagaaggtt 2100 actggcaaac tggccgtgcg ctttaaagcg ttgggtgtag ccgttgtcag aaaaattact 2160 gaatggtttg atttagccgt ggacattgct gctagtgccg ctggatggct ttgctaccag 2220 ctggtaaatg gcttatttgc agtggccaat ggtgttataa cctttgtaca ggaggtgcct 2280 gagcttgtca agaattttgt tgacaagttc aaggcatttt tcaaggtttt gatcgactct 2340 atgtcggttt ctatcttgtc tggacttact gttgtcaaga ctgcctcaaa tagggtgtgt 2400 cttgctggca gtaaggttta tgaagttgtg cagaaatctt tgtctgcata tgttatgcct 2460 gtgggttgca gcgaagccac ttgtttggtg ggtgagattg aacctgcagt ttttgaagat 2520 gatgttgttg atgtggttaa agccccatta acatatcaag gctgttgtaa gccacccact 2580 tctttcgaga agatttgtat tgtggataaa ttgtatatgg ccaagtgtgg tgatcaattt 2640 taccctgtgg ttgttgataa cgacactgtt ggcgtgttag atcagtgctg gaggtttccc 2700 tgtgcgggca agaaagtcga gtttaacgac aagcccaaag tcaggaagat accctccacc 2760 cgtaagatta agatcacctt cgcactggat gcgacctttg atagtgttct ttcgaaggcg 2820 tgttcagagt ttgaagttga taaagatgtt acattggatg agctgcttga tgttgtgctt 2880 gacgcagttg agagtacgct cagcccttgt aaggagcatg atgtgatagg cacaaaagtt 2940 tgtgctttac ttgataggtt ggcaggagat tatgtctatc tttttgatga gggaggcgat 3000 gaagtgatcg ccccgaggat gtattgttcc ttttctgctc ctgatgacga ggactgcgtt 3060 gcagcggatg ttgtagatgc agatgaaaac caagatgatg atgccgagga ctcagcagtc 3120 cttgtcgctg atacccaaga agaggacggc gttgccaagg ggcaggttga ggcggattcg 3180 gaaatttgcg ttgcgcatac tggtagtcaa gaagaattgg ctgagcctga tgctgtcgga 3240 tctcaaactc ccatcgcctc tgctgaggaa accgaagtcg gagaggcaag cgacagggaa 3300 gggattgctg aggcgaaggc aactgtgtgt gctgatgctg tagatgcctg ccccgatcaa 3360 gtggaggcat ttgaaattga aaaggtcgag gactctatct tggatgagct tcaaactgaa 3420 cttaatgcgc cagcggacaa gacctatgag gatgtcttgg cattcgatgc cgtatgctca 3480 gaggcgttgt ctgcattcta tgctgtgccg agtgatgaga cgcactttaa agtgtgtgga 3540 ttctattcgc ctgctataga gcgcactaat tgttggctgc gttctacttt gatagtaatg 3600 cagagtctac ctttggaatt taaagacttg gagatgcaaa agctctggtt gtcttacaag 3660 gccggctatg accaatgctt tgtggacaaa ctagttaaga gcgtgcccaa gtctattatc 3720 cttccacaag gtggttatgt ggcagatttt gcctatttct ttctaagcca gtgtagcttt 3780 aaagcttatg ctaactggcg ttgtttagag tgtgacatgg agttaaagct tcaaggcttg 3840 gacgccatgt ttttctatgg ggacgttgtg tctcatatgt gcaagtgtgg taatagcatg 3900 accttgttgt ctgcagatat accctacact ttgcattttg gagtgcgaga tgataagttt 3960 tgcgcttttt acacgccaag aaaggtcttt agggctgctt gtgcggtaga tgttaatgat 4020 tgtcactcta tggctgtagt agagggcaag caaattgatg gtaaagtggt taccaaattt 4080 attggtgaca aatttgattt tatggtgggt tacgggatga catttagtat gtctcctttt 4140 gaactcgccc agttatatgg ttcatgtata acaccaaatg tttgttttgt taaaggagat 4200 gttataaagg ttgttcgctt agttaatgct gaagtcattg ttaaccctgc taatgggcgt 4260 atggctcatg gtgccggcgt cgccggcgcc atagctgaaa aggcgggcag tgcttttatt 4320 aaagaaacct ccgatatggt gaaggctcag ggcgtttgcc aggttggtga atgctatgaa 4380 tctgccggtg gtaagttatg taaaaaggtg cttaacattg tagggccaga tgcgcgaggg 4440 catggcaagc aatgctattc acttttagag cgtgcttatc agcatattaa taagtgtgac 4500 aatgttgtca ctactttaat ttcggctggt atatttagtg tgcctactga tgtctcccta 4560 acttacttac ttggtgtagt gacaaagaat gtcattcttg tcagtaacaa ccaggatgat 4620 tttgatgtga tagagaagtg tcaggtgacc tccgttgctg gtaccaaagc gctatcactt 4680 caattggcca aaaatttgtg ccgtgatgta aagtttgtga cgaatgcatg tagttcgctt 4740 tttagtgaat cttgctttgt ctcaagctat gatgtgttgc aggaagttga agcgctgcga 4800 catgatatac aattggatga tgatgctcgt gtctttgtgc aggctaatat ggactgtctg 4860 cccacagact ggcgtctcgt taacaaattt gatagtgttg atggtgttag aaccattaag 4920 tattttgaat gcccgggcgg gatttttgta tccagccagg gcaaaaagtt tggttatgtt 4980 cagaatggtt catttaagga ggcgagtgtt agccaaataa gggctttact cgctaataag 5040 gttgatgtct tgtgtactgt tgatggtgtt aacttccgct cctgctgcgt agcagagggt 5100 gaagtttttg gcaagacatt aggttcagtc ttttgtgatg gcataaatgt caccaaagtt 5160 aggtgtagtg ccatttacaa gggtaaggtt ttctttcagt acagtgattt gtccgaggca 5220 gatcttgtgg ctgttaaaga tgcctttggt tttgatgaac cacaactgct gaagtactac 5280 actatgcttg gcatgtgtaa gtggccagta gttgtttgtg gcaattattt tgctttcaag 5340 cagtcaaata ataattgcta catcaacgtg gcatgtttaa tgctgcaaca cttgagttta 5400 aagtttccta agtggcaatg gcaagaggct tggaacgagt tccgctctgg taaaccacta 5460 aggtttgtgt ccttggtatt agcaaagggc agctttaaat ttaatgaacc ttctgattct 5520 atcgatttta tgcgtgtggt gctacgtgaa gcagatttga gtggtgccac gtgcaatttg 5580 gaatttgttt gtaaatgtgg tgtgaagcaa gagcagcgca aaggtgttga cgctgttatg 5640 cattttggta cgttggataa aggtgatctt gtcaggggtt ataatatcgc atgtacgtgc 5700 ggtagtaaac ttgtgcattg cacccaattt aacgtaccat ttttaatttg ctccaacaca 5760 ccagagggta ggaaactgcc cgacgatgtt gttgcagcta atatttttac tggtggtagt 5820 gtgggccatt acacgcatgt gaaatgtaaa cccaagtacc agctttatga tgcttgtaat 5880 gttaataagg tttcggaggc taagggtaat tttaccgatt gcctctacct taaaaattta 5940 aagcaaacct tctcgtctgt gctgacgact ttttatttag atgacgtaaa gtgtgtggag 6000 tataagccag atttatcgca gtattactgt gagtctggta aatattatac aaaacccatt 6060 attaaggccc aatttagaac atttgagaag gttgatggtg tctataccaa ctttaaattg 6120 gtgggacata gtattgctga aaaactcaat gctaagctgg gatttgattg taattctccc 6180 tttgtggagt ataaaattac agagtggcca acagctactg gagatgtggt gttggctagt 6240 gatgatttgt atgtaagtcg gtacttaagc gggtgcatta cttttggtaa accggttgtc 6300 tggcttggcc atgaggaagc atcgctgaaa tctctcacat attttaatag acctagtgtc 6360 gtttgtgaaa ataaatttaa cgtgttgccc gttgatgtca gtgaacccac ggacaagggg 6420 cctgtgcctg ctgcagtcct tgttaccggc gtccctggag ctgatgcgtc agctggtgcc 6480 ggtattgcca aggagcaaaa agcctgtgct tctgctagtg tggaggatca ggttgttacg 6540 gaggttcgtc aagagccatc tgtttcagct gctgatgtca aagaggttaa attgaatggt 6600 gttaaaaagc ctgttaaggt ggaaggtagt gtggttgtta atgatcccac tagcgaaacc 6660 aaagttgtta aaagtttgtc tattgttgat gtctatgata tgttcctgac agggtgtaag 6720 tatgtggttt ggactgctaa tgagttgtct cgactagtaa attcaccgac tgttagggag 6780 tatgtgaagt ggggtatggg aaagattgta acacccgcta agttgttgtt gttaagagat 6840 gagaagcaag agttcgtagc gccaaaagta gtcaaggcga aagctattgc ctgctattgt 6900 gctgtgaagt ggtttctcct ctattgtttt agttggataa agtttaatac tgacaataag 6960 gttatataca ccacagaagt agcttcaaag cttactttca agttgtgctg tttggccttt 7020 aagaatgcct tacagacgtt taattggagc gttgtgtcta ggggcttttt cctagttgca 7080 acggtctttt tactctggtt taactttttg tatgctaatg ttattttgag tgacttctat 7140 ttgcctaata ttgggcctct ccctacgttt gtgggacaga tagttgcgtg gtttaagact 7200 acatttggtg tgtcaaccat ctgtgatttc taccaggtga cggatttggg ctatagaagt 7260 tcgttttgta atggaagtat ggtatgtgaa ctatgcttct caggttttga tatgctggac 7320 aactatgatg ctataaatgt tgttcaacac gttgtagata ggcgtttgtc ctttgactat 7380 attagcctat ttaaactggt agttgagctt gtaatcggct actctcttta tactgtgtgc 7440 ttctacccac tgtttgtcct tattggaatg cagttattga ccacatggtt gcctgaattc 7500 tttatgctgg agactatgca ttggagtgct cgtttgtttg tgtttgttgc caatatgctt 7560 ccagctttta cgttactgcg attttacatc gtggtgacag ctatgtataa ggtctattgt 7620 ctttgtagac atgttatgta tggatgtagt aagcctggtt gcttgttttg ttataagaga 7680 aaccgtagtg tccgtgttaa gtgtagcacc gttgttggtg gttcactacg ctattacgat 7740 gtaatggcta acggcggcac aggtttctgt acaaagcacc agtggaactg tcttaattgc 7800 aattcctgga aaccaggcaa tacattcata actcatgaag cagcggcgga cctctctaag 7860 gagttgaaac gccctgtgaa tccaacagat tctgcttatt actcggtcac agaggttaag 7920 caggttggtt gttccatgcg tttgttctac gagagagatg gacagcgtgt ttatgatgat 7980 gttaatgcta gtttgtttgt ggacatgaat ggtctgctgc attctaaagt taaaggtgtg 8040 cctgaaacgc atgttgtggt tgttgagaat gaagctgata aagctggttt tctcggcgcc 8100 gcagtgtttt atgcacaatc gctctacaga cctatgttga tggtggaaaa gaaattaata 8160 actaccgcca acactggttt gtctgttagt cgaactatgt ttgaccttta tgtagattca 8220 ttgctgaacg tcctcgacgt ggatcgcaag agtctaacaa gttttgtaaa tgctgcgcac 8280 aactctctaa aggagggtgt tcagcttgaa caagttatgg atacctttat tggctgtgcc 8340 cgacgtaagt gtgctataga ttctgatgtt gaaaccaagt ctattaccaa gtccgtcatg 8400 tcggcagtaa atgctggcgt tgattttacg gatgagagtt gtaataactt ggtgcctacc 8460 tatgttaaaa gtgacactat cgttgcagcc gatttgggtg ttcttattca gaataatgct 8520 aagcatgtac aggctaatgt tgctaaagcc gctaatgtgg cttgcatttg gtctgtggat 8580 gcttttaacc agctatctgc tgacttacag cataggctgc gaaaagcatg ttcaaaaact 8640 ggcttgaaga ttaagcttac ttataataag caggaggcaa atgttcctat tttaactaca 8700 ccgttctctc ttaaaggggg cgctgttttt agtagaatgt tacaatggtt gtttgttgct 8760 aatttgattt gtttcattgt gttgtgggcc cttatgccaa catatgcagt gcacaaatcg 8820 gatatgcagt tgcctttata tgccagtttt aaagttatag ataacggtgt gctaagggat 8880 gtgtctgtta ctgacgcatg cttcgcaaac aaatttaatc aattcgacca atggtatgag 8940 tctacttttg gtcttgctta ttaccgcaac tctaaggctt gtcctgttgt ggttgctgta 9000 atagatcaag acattggcca taccttattt aatgttccta ccacagtttt aagatatgga 9060 tttcatgtgt tgcattttat aacccatgca tttgctactg atagcgtgca gtgttacacg 9120 ccacatatgc aaatccccta tgataatttc tatgctagtg gttgcgtgtt gtcatccctc 9180 tgtactatgc ttgcgcatgc agatggaacc ccgcatcctt attgttatac agggggtgtt 9240 atgcataatg cctctctgta tagttctttg gctcctcatg tccgttataa cctggctagt 9300 tcaaatggtt atatacgttt tcccgaagtg gttagtgaag gcattgtgcg tgttgtgcgc 9360 actcgctcta tgacctactg cagggttggt ttatgtgagg aggccgagga gggtatctgc 9420 tttaatttta atcgttcatg ggtattgaac aacccgtatt atagggccat gcctggaact 9480 ttttgtggta ggaatgcttt tgatttaata catcaagttt taggaggatt agtgcggcct 9540 attgatttct ttgccttaac ggcgagttca gtggctggtg ctatccttgc aattattgtc 9600 gttttggctt tctattattt aatcaagctt aagcgtgcct ttggtgacta cactagtgtt 9660 gtggttatca atgtaattgt gtggtgtata aattttctga tgctttttgt gtttcaggtt 9720 tatcccacat tgtcttgttt atatgcttgt ttctacttct acaccacgct ttatttccct 9780 tcggagataa gtgttgttat gcatttgcaa tggcttgtca tgtatggtgc tattatgccc 9840 ttgtggtttt gcattattta cgtggcagtc gttgtttcaa accatgcatt gtggttgttc 9900 tcttactgcc gcaaaattgg taccgaggtt cgtagtgacg gcacatttga ggaaatggcc 9960 cttactacct ttatgattac taaagaatct tattgtaagt tgaaaaactc tgtttctgat 10020 gttgctttta acaggtactt gagtctttac aacaagtacc gttacttcag tggcaaaatg 10080 gatactgccg cttatagaga ggctgcctgt tcacaactgg caaaggcaat ggaaacattt 10140 aaccataata atggtaatga tgttctctat cagcctccaa ccgcctctgt tactacatca 10200 tttttacagt ctggtatagt gaagatggtg tcgcccacct ctaaagtgga gccttgtatt 10260 gttagtgtta cttatggtaa catgacactt aatgggttgt ggttggatga taaagtttat 10320 tgcccaagac atgttatctg ttcttcagct gacatgacag accctgatta tcctaatttg 10380 ctttgtagag tgacatcaag tgatttttgt gttatgtctg gtcgtatgag ccttactgta 10440 atgtcttatc aaatgcaggg ctgccaactt gttttgactg ttacactgca aaatcctaac 10500 acgcctaagt attccttcgg tgttgttaag cctggtgaga catttactgt actggctgca 10560 tacaatggca gacctcaagg agccttccat gttacgcttc gtagtagcca taccataaag 10620 ggctcctttc tatgtggatc ctgcggttct gtaggatatg ttttaactgg cgatagtgta 10680 cgatttgttt atatgcatca gctagagttg agtactggtt gtcataccgg tactgacttt 10740 agtgggaact tttatggtcc ctatagagat gcgcaagttg tacaattgcc tgttcaggat 10800 tatacgcaga ctgttaatgt tgtagcttgg ctttatgctg ctatttttaa cagatgcaac 10860 tggtttgtgc aaagtgatag ttgttccctg gaggagttta atgtttgggc tatgaccaat 10920 ggttttagct caatcaaagc cgatcttgtc ttggatgcgc ttgcttctat gacaggcgtt 10980 acagttgaac aggtgttggc cgctattaag aggctgcatt ctggattcca gggcaaacaa 11040 attttaggta gttgtgtgct tgaagatgag ctgacaccaa gtgatgttta tcaacaacta 11100 gctggtgtca agctacagtc aaagcgcaca agagttataa aaggtacatg ttgctggata 11160 ttggcttcaa cgtttttgtt ctgtagcatt atctcagcat ttgtaaaatg gactatgttt 11220 atgtatgtta ctacccatat gttgggagtg acattgtgtg cactttgttt tgtaagcttt 11280 gctatgttgt tgatcaagca taagcatttg tatttaacta tgtacatcat gcctgtgtta 11340 tgcacactgt tttacaccaa ctatttggtt gtgtacaaac agagttttag aggtctagct 11400 tatgcttggc tttcacactt tgtccctgct gtagattata catatatgga tgaagtttta 11460 tatggtgttg tgttgctagt agctatggtg tttgttacca tgcgtagcat aaaccacgac 11520 gtcttttcta ttatgttctt ggttggtaga cttgtcagcc tggtatccat gtggtatttt 11580 ggagccaatt tagaggaaga ggtactattg ttcctcacat ccctatttgg cacgtacaca 11640 tggactacta tgttgtcatt ggctaccgct aaggttattg ctaaatggtt ggctgtgaat 11700 gtcttgtact tcacagacgt accgcaaatt aaattagttc tgttgagcta cttgtgtatt 11760 ggttatgtgt gttgttgtta ttggggaatc ttgtcactcc ttaatagcat ttttaggatg 11820 ccattgggcg tctacaatta taaaatctcc gttcaggagt tacgttatat gaatgctaat 11880 ggcttgcgcc cacctagaaa tagttttgag gccctgatgc ttaattttaa gctgttggga 11940 attggtggtg tgccagtcat tgaagtatct caaattcaat caagattgac ggatgttaaa 12000 tgtgctaatg ttgtgttgct taattgcctc cagcacttgc atattgcatc taattctaag 12060 ttgtggcagt attgtagtac tttgcacaat gaaatactgg ctacatctga tttgagcgtg 12120 gccttcgata agttggctca actcttagtt gttttatttg ctaatccagc agcagtggat 12180 agcaagtgcc ttgcaagtat tgaagaagtg agcgatgatt acgttcgcga caatactgtc 12240 ttgcaagcct tacagagtga atttgttaat atggctagct tcgttgagta tgaacttgct 12300 aagaagaatc tagatgaggc taaggctagc ggctctgcca atcaacagca gattaagcag 12360 ctagagaagg cgtgtaatat tgctaagtca gcatatgagc gcgacagagc tgttgctcgt 12420 aagctggaac gtatggctga tttagctctt acaaacatgt ataaagaagc tagaattaat 12480 gataagaaga gtaaggtagt gtctgcattg caaaccatgc tctttagtat ggtgcgtaag 12540 ctagataacc aagctcttaa ttctatttta gacaacgcag ttaagggttg tgtacctttg 12600 aatgcaatac catcattgac ttcgaacact ctgactataa tagtgccaga taagcaggtt 12660 tttgatcagg ttgtggataa tgtgtatgtc acctatgctg ggaatgtatg gcatatacag 12720 tttattcaag atgctgatgg tgctgttaaa caattgaatg agatagatgt taattcaacc 12780 tggcctctag tcattgctgc aaataggcat aatgaagtgt ctactgttgt tttgcagaac 12840 aatgagttga tgcctcagaa gttgagaact caggttgtca atagtggctc agatatgaat 12900 tgtaatactc ctacccagtg ttactataat actactggca cgggtaagat tgtgtatgct 12960 atacttagtg actgtgacgg cctgaagtac actaagatag taaaagaaga tggaaattgt 13020 gttgttttgg aattggatcc tccctgtaag ttttctgttc aggatgtgaa gggccttaaa 13080 attaagtacc tttactttgt gaaggggtgt aatacactgg ctagaggctg ggttgtaggc 13140 accttatcct cgacagtgag attgcaggcg ggtacggcaa ctgagtatgc ctccaactct 13200 gcaatactgt cgctgtgtgc gttttctgta gatcctaaga aaacgtactt ggattatata 13260 aaacagggtg gagttcccgt tactaattgt gttaagatgt tatgtgacca tgctggcact 13320 ggtatggcca ttactattaa gccggaggca accactaatc aggattctta tggtggtgct 13380 tccgtttgta tatattgccg ctcgcgtgtt gaacatccag atgttgatgg attgtgcaaa 13440 ttacgcggca agtttgtcca agtgccctta ggcataaaag atcctgtgtc atatgtgttg 13500 acgcatgatg tttgtcaggt ttgtggcttt tggcgagatg gtagctgttc ctgtgtaggc 13560 acaggctccc agtttcagtc aaaagacacg aactttttaa acggattcgg ggtacaagtg 13620 taaatgcccg tcttgtaccc tgtgccagtg gcttggacac tgatgttcaa ttaagggcat 13680 ttgacatttg taatgctaat cgagctggca ttggtttgta ttataaagtg aattgctgcc 13740 gcttccagcg tgtagatgag gacggcaaca agttggataa gttctttgtt gttaaaagaa 13800 ctaatttaga agtgtataac aaggagaaag aatgctatga gttgacaaaa gaatgcggtg 13860 ttgtggctga acacgagttc ttcacatttg atgtggaggg aagtcgggta ccacacatag 13920 tccgtaaaga tctttcaaag tttactatgt tagatctttg ctatgcattg cgtcattttg 13980 accgcaatga ttgttcaact cttaaggaaa ttctccttac atatgctgag tgtgaagagt 14040 cctacttcca aaagaaggac tggtatgatt ttgttgagaa tcctgatata attaatgtgt 14100 acaagaagct tggtcctata tttaatagag ccctgcttaa cactgccaag tttgcagacg 14160 cattagtgga ggcaggctta gtaggtgttt taacacttga taatcaagat ttatatggtc 14220 aatggtatga ctttggagat tttgtcaaga cagtacctgg ttgtggtgtt gccgtggcag 14280 actcttatta ttcatatatg atgccaatgc tgactatgtg tcatgcgttg gatagtgagt 14340 tgtttgttaa tggtacttat agggagtttg accttgttca gtatgatttt actgatttca 14400 agctagagct gttcactaag tattttaagc attggagtat gacctaccac ccgaacacct 14460 gtgagtgcga ggatgacagg tgcattattc attgcgccaa ttttaatata cttttcagca 14520 tggtcttacc taagacctgt tttgggcctc ttgttaggca gatatttgtg gatggtgttc 14580 ctttcgttgt gtcgatcggt taccattata aagaattagg tgttgttatg aatatggatg 14640 tggatacaca tcgttatcgc ttgtctctta aggacttgct tttgtatgct gcagaccctg 14700 cccttcatgt ggcgtctgct agtgcactgc ttgatttgcg cacatgttgt tttagcgttg 14760 cagctattac aagtggcgta aaatttcaaa cagttaaacc tggaaatttt aatcaggatt 14820 tctacgagtt tattttgagt aaaggcctgc ttaaagaggg gagctccgtt gatttgaagc 14880 acttcttctt tacgcaggat ggtaatgctg ctattactga ttacaattac tacaagtata 14940 atctacccac catggtggat attaagcagt tgttgtttgt tttagaagtt gttaataagt 15000 acttcgagat ctatgagggt gggtgtatac ccgcaacaca ggtcattgtt aataattatg 15060 acaagagtgc tggctatcca tttaataaat ttggaaaggc caggctctat tatgaggcat 15120 tatcatttga ggagcaggat gaaatttatg cgtataccaa acgcaatgtc ctgccgaccc 15180 taactcaaat gaatcttaaa tatgctatta gtgctaagaa tagggcccgc accgttgctg 15240 gtgtctctat tctcagtact atgactggca gaatgtttca tcaaaagtgt ctaaagagta 15300 tagcagctac tcgcggtgtt cctgtagtta taggcaccac gaagttctat ggcggttggg 15360 atgatatgtt acgccgcctt attaaagatg ttgatagtcc tgtactcatg ggttgggact 15420 atcctaaatg tgatcgtgct atgccaaaca tactgcgtat tgttagtagt ttggtgctag 15480 cccgtaaaca tgattcgtgc tgttcgcata cggatagatt ctatcgtctt gcgaacgagt 15540 gcgcccaagt tttgagtgaa attgttatgt gtggtggttg ttattatgtt aaaccaggtg 15600 gcactagtag tggggatgca accactgctt ttgctaattc tgtgtttaac atttgtcaag 15660 ctgtttccgc caatgtatgc tcgcttatgg catgcaatgg acacaaaatt gaagatttga 15720 gtatacgcga gttacaaaag cgcctatact ctaatgtcta tcgtgcggac catgttgacc 15780 ccgcatttgt tagtgagtat tatgagtttt taaacaagca ttttagtatg atgattttga 15840 gtgatgatgg tgttgtgtgt tataattcag agtttgcgtc caagggttat attgctaata 15900 taagtgcctt tcaacaggta ttatattatc aaaacaacgt gtttatgtct gaggccaaat 15960 gttgggtaga aacagacatc gaaaagggac cgcatgaatt ttgttctcaa catacaatgc 16020 tagtcaagat ggatggtgat gaagtctacc ttccataccc tgatccttcg agaatcttag 16080 gagcaggctg ttttgttgat gatttactca agactgatag cgttctcttg atagagcgtt 16140 tcgtaagtct tgcaattgat gcttatcctt tagtatacca tgagaaccca gagtatcaaa 16200 atgtgttccg ggtatattta gaatacatca agaagctgta caatgatctc ggtaatcaga 16260 tcctggacag ctacagtgtt attttaagta cttgtgatgg tcaaaagttt actgacgaga 16320 cgttttacaa gaacatgtat ttaagaagtg cagtgctgca aagcgttggt gcctgcgttg 16380 tctgtagttc tcaaacatca ttacgttgtg gcagttgcat acgcaagcct ttgctgtgtt 16440 gcaaatgcgc ctatgatcat gttatgtcca ctgatcataa atatgtcctg agtgtgtcac 16500 catatgtgtg taattcaccg ggatgtgatg taaatgatgt taccaaattg tatttaggtg 16560 gtatgtcata ttattgtgag gaccataaac cacagtattc attcaaattg gtgatgaatg 16620 gtatggtttt tggtttatat aagcagtctt gtactggttc gccctacata gaggatttta 16680 ataaaatcgc tagttgcaaa tggacagaag tcgatgatta tgtgctagct aatgaatgca 16740 ccgaacgcct taaattgttt gccgcagaaa cgcagaaggc cacagaagag gcctttaagc 16800 aatgttatgc gtcagcaacg atccgtgaga tcgtgagcga tcgggagtta attttatctt 16860 gggaaattgg taaagtccgc ccgccactta ataaaaatta cgtgttcacc ggctaccatt 16920 ttactaataa tggtaagaca gttttaggtg agtatgtttt tgataagagt gagttgacta 16980 atggtgtgta ttatcgcgcc acaaccactt ataagttatc tgtaggtgat gtgttcattt 17040 taacatcaca cgcagtgtct agtttaagtg ctcctacatt agtaccgcag gagaattata 17100 ctagcattcg ttttgctagt gtttatagtg tgcctgagac gtttcagaat aatgtgccta 17160 attatcagca cattggaatg aagcgctatt gtactgtaca gggaccgcct ggtactggta 17220 agtcccatct agccattggg ctagctgttt attattgtac agcgcgcgtg gtgtataccg 17280 ctgctagcca tgctgcagtt gacgcgctgt gtgaaaaggc acataaattt ctcaacatca 17340 acgactgcac gcgtattgtt cctgcaaagg tgcgtgtaga ttgttatgat aaattcaagg 17400 tcaatgacac cactcgcaag tatgtgttta ctacaataaa tgcattacct gagttggtga 17460 ctgacattat tgtcgttgat gaagttagta tgcttaccaa ctatgagctg tctgttatta 17520 acagtcgtgt tagggctaag cattatgtgt atattggcga cccggcgcag ttacctgcac 17580 cacgtgtgct actgaataag ggaactctag aacctagata ttttaattcc gttaccaagc 17640 taatgtgttg tttgggtcca gatattttct tgggcacctg ttatagatgc cctaaggaga 17700 ttgtggatac ggtgtcagcc ttggtttata ataataagct gaaggctaaa aatgataata 17760 gctccatgtg ctttaaggtt tattataagg gccagactac acatgagagt tctagtgctg 17820 ttaatatgca gcaaatacat ttaatttcca agtttctgaa ggcaaacccc agttggagta 17880 acgccgtatt tattagtcct tataactcgc agaactatgt tgctaagaga gtcttgggat 17940 tacaaaccca gacagtagac tcagcgcagg gttctgaata tgattttgtt atctactcac 18000 agactgcgga aacagcgcat tctgtcaatg taaatagatt caatgttgct attacacgtg 18060 ctaagaaggg tattctctgt gtcatgagta gtatgcaatt atttgagtct cttaatttta 18120 ctacactgac gttggataag attaacaatc cacgattaca gtgtactaca aatttgttta 18180 aggattgtag caggagctat gtaggatatc acccagccca tgcaccatcc tttttggcag 18240 ttgatgacaa atataaggta ggcggtgatt tagccgtttg ccttaatgtt gctgattctg 18300 ctgtcactta ttcgcggctt atatcactca tgggattcaa gcttgacttg acccttgatg 18360 gttattgtaa gctgtttata actagagatg aagctatcaa acgtgttaga gcctgggttg 18420 gcttcgatgc agaaggtgcc catgcgatac gtgatagcat tgggacaaat ttcccattac 18480 aattaggctt ttcgactgga attgattttg ttgtcgaagc cactggaatg tttgctgaga 18540 gagatggtta tgtctttaaa aaggcagccg cacgagctcc tcctggcgaa caatttaaac 18600 accttatccc acttatgtca agagggcaga aatgggatgt ggttcgcatt agaatagtac 18660 aaatgttgtc agaccaccta gtggatttgg cagacagtgt tgtacttgtg acgtgggctg 18720 ccagctttga gctcacatgt ttgcgatatt tcgctaaagt tggaagagaa gttgtgtgta 18780 gtgtctgcac caagcgtgcg acatgtttta attctagaac tggatactat ggatgctggc 18840 gacatagtta ttcctgtgat tacctgtaca acccactaat agttgacatt caacagtggg 18900 gatatacagg atctttaact agcaatcatg atcctatttg cagcgtgcat aagggtgctc 18960 atgttgcatc atctgatgct atcatgaccc ggtgtctagc tgttcatgat tgcttttgta 19020 agtctgttaa ttggaattta gaatacccca ttatttcaaa tgaggtcagt gttaatacct 19080 cctgcaggtt attgcagcgc gtaatgttta gggctgcgat gctatgcaat aggtatgatg 19140 tgtgttatga cattggcaac cctaaaggtc ttgcctgtgt caaaggatat gattttaagt 19200 tctatgacgc ctcccctgtt gttaagtctg ttaaacagtt tgtttacaaa tacgaggcac 19260 ataaagatca atttttagat ggtttgtgta tgttttggaa ctgcaatgtg gataagtatc 19320 cagcgaatgc agttgtgtgt aggtttgaca cgcgtgtgtt gaacaaatta aatctccctg 19380 gctgtaatgg tggcagtttg tatgttaaca aacatgcatt ccacaccagt ccctttaccc 19440 gggctgcctt cgagaatttg aagcctatgc ctttctttta ttattcagat acgccctgtg 19500 tgtatatgga aggcatggaa tctaagcagg tcgattatgt cccattgaga agcgctacat 19560 gcatcacaag atgcaattta ggtggcgctg tttgtttaaa acatgctgag gagtatcgtg 19620 agtaccttga gtcttacaat acggcaacca cagcgggttt tactttttgg gtctataaga 19680 cttttgattt ttacaacctt tggaatactt ttactaggct ccaaagttta gaaaatgtag 19740 tgtataacct ggtcaacgct ggacactttg atggccgggc gggtgaactg ccttgtgctg 19800 ttataggtga gaaagtcatt gccaagattc aaaatgagga tgtcgtggtc tttaaaaata 19860 acacgccatt ccccactaat gtggctgtcg aattatttgc taagcgcagt attcggcccc 19920 accccgagct taagctcttt agaaatttga atattgacgt gtgctggagt cacgtccttt 19980 gggattatgc taaggatagt gtgttttgca gttcgacgta taaggtctgc aaatacacag 20040 atttacagtg cattgaaagc ttgaatgtac tttttgatgg tcgtgataat ggtgctcttg 20100 aagcttttaa gaagtgccgg aatggcgtct acattaacac gacaaaaatt aaaagtctgt 20160 cgatgattaa aggcccacaa cgtgccgatt tgaatggcgt agttgtggag aaagttggag 20220 attctgatgt ggaattttgg tttgctgtgc gtaaagacgg tgacgatgtt atcttcagcc 20280 gtacagggag ccttgaaccg agccattacc ggagcccaca aggtaatccg ggtggtaatc 20340 gcgtgggtga tctcagcggt aatgaagctc tagcgcgtgg cactatcttt actcaaagca 20400 gattattatc ttctttcaca cctcgatcag agatggagaa agattttatg gatttagatg 20460 atgatgtgtt cattgcaaaa tatagtttac aggactacgc gtttgaacac gttgtttatg 20520 gtagttttaa ccagaagatt attggaggtt tgcatttgct tattggctta gcccgtaggc 20580 agcaaaaatc caatctggta attcaagagt tcgtgacata cgactctagc attcattcgt 20640 actttatcac tgacgagaac agtggtagta gtaagagtgt gtgcactgtt attgatttat 20700 tgttagatga ttttgtggac attgtaaagt ccctgaatct aaagtgtgtg agtaaggttg 20760 ttaatgttaa tgtggatttt aaggacttcc agtttatgtt gtggtgcaat gaggagaagg 20820 tcatgacttt ctatcctcgt ttgcaggctg ctgctgactg gaaacctggt tatgttatgc 20880 ctgtcttata taagtatttg gaatcgcctc tggaaagagt aaacctctgg aattatggca 20940 agccgattac tttacctaca ggatgtatga tgaatgttgc taagtatact caattatgtc 21000 aatatttgag cactacaaca ttagcagttc cggctaatat gcgtgtctta caccttggtg 21060 ccggttcgga taagggtgtt gcccctgggt ctgcagttct taggcagtgg ctaccagcgg 21120 gaagtattct tgtagataat gatgtgaatc catttgtgag tgacagtgtc gcctcatatt 21180 atggaaattg tataacctta ccctttgatt gtcagtggga tctgataatt tctgatatgt 21240 acgaccctct tactaagaac attggggagt acaacgtgag taaagatgga ttctttactt 21300 acctctgtca tttaattcgt gacaagttgg ctctgggtgg cagtgttgcc ataaaaataa 21360 cagagttttc ttggaacgct gagttatata gtttaatggg gaagtttgcg ttctggacaa 21420 tcttttgcac caacgtaaac gcctcttcaa gtgaaggatt tttgattggc ataaattggt 21480 tgaataagac ccgtaccgaa attgacggta aaaccatgca tgccaattat ctgttttgga 21540 gaaatagtac aatgtggaat ggaggggctt acagtctctt tgacatgagt aagttccctt 21600 tgaaagcggc tggtacggct gttgttagcc ttaaaccaga ccaaataaat gacttagtcc 21660 tctccttgat tgagaagggc aagttattag tgcgtgatac acgcaaagaa gtttttgttg 21720 gcgatagcct agtaaatgtc aaataaatct atacttgtcg tggctgtgaa aatggccttt 21780 gctgacaagc ctaatcattt cataaacttt cccctggccc aatttagtgg ctttatgggt 21840 aagtatttaa agctacagtc tcaacttgtg gaaatgggtt tagactgtaa attacagaag 21900 gcaccacatg ttagtattac cctgcttgat attaaagcag accaatacaa acaggtggaa 21960 tttgcaatac aagaaataat agatgatctg gcggcatatg agggagatat tgtctttgac 22020 aaccctcaca tgcttggcag atgccttgtt cttgatgtta gaggatttga agagttgcat 22080 gaagatattg ttgaaattct ccgcagaagg ggttgcacgg cagatcaatc cagacactgg 22140 attccgcact gcactgtggc ccaatttgac gaagaaagag aaacaaaagg aatgcaattc 22200 tatcataaag aacccttcta cctcaagcat aacaacctat taacggatgc tgggcttgag 22260 ctcgtgaaga taggttcttc caaaatagat gggttttatt gtagtgaact gagtgtttgg 22320 tgtggtgaga ggctttgtta taagcctcca acacccaaat tcagtgatat atttggctat 22380 tgctgcatag ataaaatacg tggtgattta gaaataggcg acctgccgca ggatgatgag 22440 gaagcgtggg ccgagctaag ttaccactat caaagaaaca cctacttctt cagacatgtg 22500 cacgataata gcatctattt tcgtaccgtg tgtagaatga agggttgtat gtgttgattt 22560 gtttttacac tattagtgta ataagcttat tattttgttg aaaagggcag gatgtgcata 22620 gctatggctc ctcgcacact gcttttgctg atttgatgtc agctggtgtt tgggttcaat 22680 gaacctctta acatcgtttc acatttaaat gatgactggt ttctatttgg tgacagtcgg 22740 tccgactgta cctatgtaga aaataacggt catcctaaat tagattggct tgacctcgac 22800 ccaaagttgt gtaattcagg aaagatttcc gcaaagagtg gtaactctct ctttaggagt 22860 tttcacttca ctgattttta caattatacg ggtgagggat accaaattgt attttatgaa 22920 ggagttaatt ttagtcccag ccatggcttt aaatgcctgg ctcatggaga taataaaaga 22980 tggatgggca ataaagctcg attttatgcc cgagtgtatg agaagatggc ccaatatagg 23040 agcctatcgt ttgttaatgt gtcttatgcc tatggaggta atgcaaagcc cgcctccatt 23100 tgcaaagaca atactttaac actcaataac cccaccttca tatcgaagga gtctaattat 23160 gttgattact actacgagag tgaggctaat ttcacactag aaggttgtga tgaatttata 23220 gtaccgctct gtggttttaa tggccattcc aagggctcgt cgtcggatgc tgccaataaa 23280 tattatactg actctcagag ttactataat atggatattg gtgtcttata tgggttcaat 23340 tcgaccttgg atgttggcaa cactgctaag gatccgggtc ttgatctcac ttgtaggtat 23400 cttgcattga ctcctggtaa ttataaggct gtgtccttag aatatttgtt aagcttaccc 23460 tcaaaggcta tttgcctcca taagacaaag cgctttatgc ctgtgcaggt agttgactca 23520 aggtggagta gcatccgcca gtcagacaat atgaccgctg cagcctgtca gctgccatat 23580 tgtttctttc gcaacacatc tgcgaattat agtggtggca cacatgatgc gcaccatggt 23640 gattttcatt tcaggcagtt attgtctggt ttgttatata atgtttcctg tattgcccag 23700 cagggtgcat ttctttataa taatgtgtcg tcctcttggc cagcctatgg gtacggtcat 23760 tgtccaacgg cagctaacat tggttatatg gcacctgttt gtatctatga ccctctcccg 23820 gtcatactgc taggtgtgtt attgggtata gctgtgttga ctattgtgtt tctgatgttt 23880 tattttatga cggatagcgg tgttagattg catgaggcat aatctaaaca tgtttgtttt 23940 tcttgtttta ttgccactag tctctagtca gtgtgttaat cttacaacca gaactcaatt 24000 accccctgca tacactaatt ctttcacacg tggtgtttat taccctgaca aagttttcag 24060 atcctcagtt ttacattcaa ctcaggactt gttcttacct ttcttttcca atgttacttg 24120 gttccatgct atacatgtct ctgggaccaa tggtactaag aggtttgata accctgtcct 24180 accatttaat gatggtgttt actttgcttc cactgagaag tctaacataa taagaggctg 24240 gatttttggt actactttag attcgaaaac ccagtcccta cttattgtta ataacgctac 24300 taatgttgtt atcaaagtct gtgaatttca attttgtaac gatccatttt tgggtgttta 24360 ttaccacaaa aacaacaaaa gttggatgga aagtgagttc agagtttatt ctagtgcgaa 24420 taattgcact tttgaatacg tctctcagcc ttttcttatg gaccttgaag gaaaacaggg 24480 taatttcaaa aatcttaggg aatttgtgtt caagaatatt gatggttact tcaagatata 24540 ctctaagcac acgcctatta atttagtgcg tgatctccct cagggttttt cggctttaga 24600 accattggta gatttgccaa taggtattaa catcactagg tttcaaactt tacttgcttt 24660 acatagaagt tatttaactc ctggtgattc ttcttcaggt tggacagctg gtgctgcagc 24720 ttattatgtg ggttatcttc aacctaggac ttttctactg aagtacaatg aaaatggaac 24780 cattacagat gctgtagact gtgcacttga ccctctctca gaaacaaagt gtacgttgaa 24840 atccttcact gtagaaaaag gaatctatca aacttctaac tttagagtcc aaccaacaga 24900 atctattgtt agatttccta acatcacaaa cttgtgccct tttggtgaag tttttaacgc 24960 caccagattt gcatctgttt atgcttggaa caggaagaga atcagcaact gtgttgctga 25020 ttattctgtc ctgtataatt ccgcatcatt ttccactttt aagtgttatg gagtgtctcc 25080 tactaaatta aatgatctct gctttactaa tgtctatgca gattcatttg taattagagg 25140 tgatgaagtc agacaaatcg ctccagggca aactggaaag attgctgatt ataactacaa 25200 attaccagat gattttacag gctgcgttat agcttggaat tctaacaatc ttgattctaa 25260 ggttggtggt aattataatt acctgtacag attgtttagg aagtctaatc tcaaaccttt 25320 tgagagagat atttcaactg aaatctatca ggccggtagc acaccttgta atggtgttga 25380 aggttttaat tgttactttc ctctgcaatc atatggtttc caacccacta atggtgttgg 25440 ttaccaacca tacagagtag tagtactttc ttttgaactt ctacatgcac cagcaactgt 25500 ttgtggacct aaaaagtcta ctaatttggt taagaacaag tgtgtcaatt tcaacttcaa 25560 tggtttaaca ggcacaggtg ttcttactga gtctaacaaa aagtttctgc ctttccaaca 25620 atttggcaga gacattgctg acactactga tgctgttcgt gatccacaaa cacttgagat 25680 tcttgacatt acaccatgtt cttttggtgg tgtcagtgtt ataacaccag gaacaaatac 25740 ttctaaccag gttgctgttc tttatcagga tgttaactgc acagaagtcc ctgttgctat 25800 tcatgcagat caacttactc ctacttggcg tgtttattct acaggttcta atgtttttca 25860 aacacgtgca ggctgtttaa taggggctga acatgtcaac aactcatatg agtgtgacat 25920 acccattggt gcaggtatat gcgctagtta tcagactcag actaattctc ctcggagagc 25980 aagaagtgta gctagtcaat ccatcattgc ctacactatg tcacttggtg cagaaaattc 26040 agttgcttac tctaataact ctattgccat acccacaaat tttactatta gcgttaccac 26100 agaaattcta ccagtgtcta tgaccaagac atcagtagat tgtacaatgt acatttgtgg 26160 tgattcaact gaatgcagca atcttttgtt gcaatatggc agtttttgta cacaattaaa 26220 ccgtgcttta actggaatag ctgttgaaca agacaaaaac acccaagaag tttttgcaca 26280 agtcaaacaa atttacaaga caccaccaat taaagatttt ggcggtttta attttagcca 26340 gatactgcca gatccatcaa aaccaagcaa gaggtcattt attgaagatc tactgttcaa 26400 caaagtgaca cttgcagatg ctggcttcat caaacaatat ggtgattgcc ttggtgatat 26460 tgctgctaga gacctcattt gtgcacaaaa gtttaacggc cttactgttt tgccaccttt 26520 gctcacagat gaaatgattg ctcaatacac ttctgcactg ttagcaggta caatcacttc 26580 tggttggact tttggtgcag gtgctgcatt acaaatacca tttgctatgc aaatggctta 26640 taggtttaat ggtattggag ttacacagaa tgttctctat gagaaccaaa aattgattgc 26700 caaccaattt aatagtgcta ttggcaaaat tcaagactca ctttcttcca cagcaagtgc 26760 acttggaaaa cttcaagatg tggtcaacca aaatgcacaa gctttaaaca cgcttgttaa 26820 acaacttagc tccaattttg gtgcaatttc aagtgtttta aacgacatcc tttcacgtct 26880 tgacaaagtt gaggctgaag tgcaaattga taggttgatc acaggcagac ttcaaagttt 26940 gcagacatat gtgactcaac aattaattag agctgcagaa atcagagctt ctgctaatct 27000 tgctgctact aaaatgtcag agtgtgtact tggacaatca aaaagagttg acttttgcgg 27060 aaagggctat catcttatgt catttcctca gtcagcacct catggtgtcg tctttttgca 27120 tgtgacttat gtccctgcac aagaaaagaa cttcacaact gctcctgcca tttgtcatga 27180 tggaaaagca cactttcctc gtgaaggtgt ctttgtttca aatggcacac actggtttgt 27240 aacacaaagg aatttttatg aaccacaaat cattactaca gacaacacat ttgtgtctgg 27300 taactgtgat gttgtaatag gaattgtcaa caacacagtt tatgatcctt tgcaacctga 27360 attagactca ttcaaggagg agcttgataa atacttcaag aaccatacct caccagatgt 27420 tgatttaggt gacatctctg gcattaatgc ttcagttgta aacattcaga aagaaatcga 27480 ccgcctcaat gaggttgcca agaatttaaa tgaatctctc atcgatctcc aagaacttgg 27540 aaagtatgag cagtatataa aatggccatg gtacatttgg ctaggtttta tagctggctt 27600 gattgccata gtaatggtga caattatgct ttgctgtatg accagttgct gtagttgtct 27660 caagggctgt tgttcttgtg gatcctgctg caaatttgac gaggacgact ctgagccagt 27720 gctcaaagga gtcaaattac attacacata actatcacag cctctcctgg aaagacagaa 27780 aatctaaaca atttatagca ttctcattgc tacctggccc cgtaagaggc agtcatagct 27840 atggccgtgt tggtcctaag gctacattgg ctgctgtctt tattggtcca tttattgtag 27900 catgtatgct aggcattggc ctagtttatt tattgcaatt gcaagttcaa atttttcatg 27960 ttaaggatac catacgtgtg actggcaagc cagccactgt gtcttatact acaagtacac 28020 cagtaacacc gagcgcgacg acgctcgatg gtactacgta tactttaatt agacccacta 28080 gctcttatac aagagtttat cttggtactc caagaggttt tgattatagt acatttgggc 28140 ctaagaccct agattatgtt actaatctaa acctcatctt aattctggtc gtccatatac 28200 ttttaaggca ttgtccaggc atatgaggcc aacagccaca tggatttggc atgtgagtga 28260 tgcatggtta cgccgcacgc gggactttgg tgtcattcgc ctagaagatt tttgttttca 28320 atttaattat agccaacccc gagttggtta ttgtagagtt cctttaaagg cttggtgtag 28380 caaccagggt aaatttgcag cgcagtttac cctaaaaagt tgcgaaaaac caggtcacga 28440 aaaatttatt actagcttca cggcctacgg cagaactgtc caacaggccg ttagcaagtt 28500 agtagaagaa gctgttgatt ttattctttt tagggccacg cagctcgaaa gaaatgttta 28560 atttattcct tacagacaca gtatggtatg tggggcagat tatttttata ttcgcagtgt 28620 gtttgatggt caccataatt gtggttgcct tccttgcgtc tatcaaactt tgtattcaac 28680 tttgcggttt atgtaatact ttggtgctgt ccccttctat ttatttgtat gataggagta 28740 agcagcttta taagtactat aatgaagaaa tgagactgcc cctattagag gtggatgata 28800 tctaatccaa acattatgag tagtactact caggccccag agcccgtcta tcaatggacc 28860 gccgacgagg cagttcaatt ccttaaggaa tggaacttct cgttgggcat tatactactc 28920 tttattacta tcatactaca gttcggttac acgagccgta gcatgtttat ttatgttgtg 28980 aaaatgataa tcttgtggtt aatgtggcca ctgactattg ttttgtgtat tttcaattgc 29040 gtgtatgcgc taaataatgt gtatcttgga ttttctatag tgtttactat agtgtccatt 29100 gtaatctgga tcatgtattt tgtgaacagc ataaggttgt ttatcaggac tggtagctgg 29160 tggagcttca accccgaaac aaacaacctt atgtgtatag atatgaaagg taccgtgtat 29220 gttagaccca ttattgagga ttaccataca ctaacagcca ctattattcg tggccacctc 29280 tacatgcaag gtgttaagct aggcaccggt ttctctttgt ctgacttgcc cgcttatgtt 29340 acagttgcta aggtgtcaca cctttgcact tataagcgcg cattcttaga caaggtagac 29400 ggtgttagcg gttttgctgt ttatgtgaag tccaaggtcg gaaattaccg actgccctca 29460 aacaaaccga gtggcgcgga caccgcattg ttgagaacct aatctaaact ttaaggagag 29520 aatgaatcct atgtcggcgc tcggtggtaa cccctcgcga gaaagtcggg ataggacact 29580 ctctatcaga atggatgtct tgctgtcata acagatagag aaggttgtgg cagaccctgt 29640 atcaattagt tgaaagagat tgcaaaatag agaatgtgtg agagaagtta gcaaggtcct 29700 acgtctaacc ataagaacgg cgataggcgc cccctgggaa cagctcacat cagggtacta 29760 ttcctgcaat gccctagtaa atgaatgaag ttgatcatgg ccaattggaa gaatcacaaa 29820 aaaaaaaaaa aaaacggccg gttt 29844 <210> 34 <211> 27671 <212> DNA <213> Artificial Sequence <220> <223> COVAX191_delta_HEN_RNA <400> 34 gtataagagt gattggcgtc cgtacgtacc ctctcaactc taaaactctt gtagtttaaa 60 tctaatctaa actttataaa cggcacttcc tgcgtgtcca tgcccgcggg cctggtcttg 120 tcatagtgct gacatttgta gttccttgac tttcgttctc tgccagtgac gtgtccattc 180 ggcgccagca gcccacccat aggttgcata atggcaaaga tgggcaaata cggcctgggc 240 ttcaaatggg ccccagaatt tccatggatg cttccgaacg catcggagaa gttgggtaac 300 cctgagaggt cagaggagga tgggttttgc ccctctgctg cgcaagaacc gaaagttaaa 360 ggaaaaactt tggttaatca cgtgagggtg aattgtagcc ggcttccagc tttggaatgc 420 tgtgttcagt ctgccataat ccgtgatatt tttgtagatg aggatcccca gaaggtggag 480 gcctcaacta tgatggcatt gcagttcggt agtgccgtct tggttaagcc atccaagcgc 540 ttgtctattc aggcatggac taatttgggt gtgcttccca aaacagctgc catggggttg 600 ttcaagcgcg tctgcctgtg taacaccagg gagtgctctt gtgacgccca cgtggccttt 660 caccttttta cggtccaacc cgatggtgta tgcctgggta atggccgttt tataggctgg 720 ttcgttccag tcacagccat accggagtat gcgaagcagt ggttgcaacc ctggtccatc 780 cttcttcgta agggtggtaa caaagggtct gtgacatccg gccacttccg ccgcgctgtt 840 accatgcctg tgtatgactt taatgtagag gatgcttgtg aggaggttca tcttaacccg 900 aagggtaagt actcctgcaa ggcgtatgcc ctgctgaagg gctatcgcgg tgttaagccc 960 atcctgtttg tggaccagta tggttgcgac tatactggat gtctcgccaa gggtcttgag 1020 gactatggcg atctcacctt gagtgagatg aaggagttgt tccctgtgtg gcgtgactcc 1080 ttggatagtg aagtccttgt ggcttggcac gttgatcgag atcctcgggc tgctatgcgt 1140 ctgcagactc ttgctactgt acgttgcatt gattatgtgg gccaaccgac cgaggatgtg 1200 gtggatggag atgtggtagt gcgtgagcct gctcatcttc tcgcagccaa tgccattgtt 1260 aaaagactcc cccgtttggt ggagactatg ctgtatacgg attcgtccgt tacagaattc 1320 tgttataaaa ccaagctgtg tgaatgcggt tttatcacgc agtttggcta tgtggattgt 1380 tgtggtgaca cctgtgattt tcgtgggtgg gttgccggca atatgatgga tggctttcca 1440 tgtccagggt gtaccaaaaa ttatatgccc tgggaattgg aggcccagtc atcaggtgtt 1500 ataccagaag gaggtgttct attcactcag agcactgata cagtgaatcg tgagtccttt 1560 aagctctacg gtcatgctgt tgtgcctttt ggttctgctg tgtattggag cccttgccca 1620 ggtatgtggc ttccagtaat ttggtcgtcg gttaagtcat actctggttt gacttataca 1680 ggagtagttg gttgtaaggc aattgttcaa gagacagacg ctatatgtcg ttctctgtat 1740 atggattatg tccagcacaa gtgtggcaat ctcgagcaga gagctatcct tggattggac 1800 gatgtctatc atagacagtt gcttgtgaat aggggtgact atagtctcct ccttgagaat 1860 gtggatttgt ttgttaagcg gcgcgctgaa tttgcttgca aattcgccac ctgtggagat 1920 ggtcttgtac ccctcctact agatggttta gtgccccgca gttattattt gattaagagt 1980 ggtcaagctt tcacctctat gatggttaat tttagccatg aggtgactga catgtgtatg 2040 gacatggctt tattgttcat gcatgatgtt aaagtggcca ctaagtatgt taagaaggtt 2100 actggcaaac tggccgtgcg ctttaaagcg ttgggtgtag ccgttgtcag aaaaattact 2160 gaatggtttg atttagccgt ggacattgct gctagtgccg ctggatggct ttgctaccag 2220 ctggtaaatg gcttatttgc agtggccaat ggtgttataa cctttgtaca ggaggtgcct 2280 gagcttgtca agaattttgt tgacaagttc aaggcatttt tcaaggtttt gatcgactct 2340 atgtcggttt ctatcttgtc tggacttact gttgtcaaga ctgcctcaaa tagggtgtgt 2400 cttgctggca gtaaggttta tgaagttgtg cagaaatctt tgtctgcata tgttatgcct 2460 gtgggttgca gcgaagccac ttgtttggtg ggtgagattg aacctgcagt ttttgaagat 2520 gatgttgttg atgtggttaa agccccatta acatatcaag gctgttgtaa gccacccact 2580 tctttcgaga agatttgtat tgtggataaa ttgtatatgg ccaagtgtgg tgatcaattt 2640 taccctgtgg ttgttgataa cgacactgtt ggcgtgttag atcagtgctg gaggtttccc 2700 tgtgcgggca agaaagtcga gtttaacgac aagcccaaag tcaggaagat accctccacc 2760 cgtaagatta agatcacctt cgcactggat gcgacctttg atagtgttct ttcgaaggcg 2820 tgttcagagt ttgaagttga taaagatgtt acattggatg agctgcttga tgttgtgctt 2880 gacgcagttg agagtacgct cagcccttgt aaggagcatg atgtgatagg cacaaaagtt 2940 tgtgctttac ttgataggtt ggcaggagat tatgtctatc tttttgatga gggaggcgat 3000 gaagtgatcg ccccgaggat gtattgttcc ttttctgctc ctgatgacga ggactgcgtt 3060 gcagcggatg ttgtagatgc agatgaaaac caagatgatg atgccgagga ctcagcagtc 3120 cttgtcgctg atacccaaga agaggacggc gttgccaagg ggcaggttga ggcggattcg 3180 gaaatttgcg ttgcgcatac tggtagtcaa gaagaattgg ctgagcctga tgctgtcgga 3240 tctcaaactc ccatcgcctc tgctgaggaa accgaagtcg gagaggcaag cgacagggaa 3300 gggattgctg aggcgaaggc aactgtgtgt gctgatgctg tagatgcctg ccccgatcaa 3360 gtggaggcat ttgaaattga aaaggtcgag gactctatct tggatgagct tcaaactgaa 3420 cttaatgcgc cagcggacaa gacctatgag gatgtcttgg cattcgatgc cgtatgctca 3480 gaggcgttgt ctgcattcta tgctgtgccg agtgatgaga cgcactttaa agtgtgtgga 3540 ttctattcgc ctgctataga gcgcactaat tgttggctgc gttctacttt gatagtaatg 3600 cagagtctac ctttggaatt taaagacttg gagatgcaaa agctctggtt gtcttacaag 3660 gccggctatg accaatgctt tgtggacaaa ctagttaaga gcgtgcccaa gtctattatc 3720 cttccacaag gtggttatgt ggcagatttt gcctatttct ttctaagcca gtgtagcttt 3780 aaagcttatg ctaactggcg ttgtttagag tgtgacatgg agttaaagct tcaaggcttg 3840 gacgccatgt ttttctatgg ggacgttgtg tctcatatgt gcaagtgtgg taatagcatg 3900 accttgttgt ctgcagatat accctacact ttgcattttg gagtgcgaga tgataagttt 3960 tgcgcttttt acacgccaag aaaggtcttt agggctgctt gtgcggtaga tgttaatgat 4020 tgtcactcta tggctgtagt agagggcaag caaattgatg gtaaagtggt taccaaattt 4080 attggtgaca aatttgattt tatggtgggt tacgggatga catttagtat gtctcctttt 4140 gaactcgccc agttatatgg ttcatgtata acaccaaatg tttgttttgt taaaggagat 4200 gttataaagg ttgttcgctt agttaatgct gaagtcattg ttaaccctgc taatgggcgt 4260 atggctcatg gtgccggcgt cgccggcgcc atagctgaaa aggcgggcag tgcttttatt 4320 aaagaaacct ccgatatggt gaaggctcag ggcgtttgcc aggttggtga atgctatgaa 4380 tctgccggtg gtaagttatg taaaaaggtg cttaacattg tagggccaga tgcgcgaggg 4440 catggcaagc aatgctattc acttttagag cgtgcttatc agcatattaa taagtgtgac 4500 aatgttgtca ctactttaat ttcggctggt atatttagtg tgcctactga tgtctcccta 4560 acttacttac ttggtgtagt gacaaagaat gtcattcttg tcagtaacaa ccaggatgat 4620 tttgatgtga tagagaagtg tcaggtgacc tccgttgctg gtaccaaagc gctatcactt 4680 caattggcca aaaatttgtg ccgtgatgta aagtttgtga cgaatgcatg tagttcgctt 4740 tttagtgaat cttgctttgt ctcaagctat gatgtgttgc aggaagttga agcgctgcga 4800 catgatatac aattggatga tgatgctcgt gtctttgtgc aggctaatat ggactgtctg 4860 cccacagact ggcgtctcgt taacaaattt gatagtgttg atggtgttag aaccattaag 4920 tattttgaat gcccgggcgg gatttttgta tccagccagg gcaaaaagtt tggttatgtt 4980 cagaatggtt catttaagga ggcgagtgtt agccaaataa gggctttact cgctaataag 5040 gttgatgtct tgtgtactgt tgatggtgtt aacttccgct cctgctgcgt agcagagggt 5100 gaagtttttg gcaagacatt aggttcagtc ttttgtgatg gcataaatgt caccaaagtt 5160 aggtgtagtg ccatttacaa gggtaaggtt ttctttcagt acagtgattt gtccgaggca 5220 gatcttgtgg ctgttaaaga tgcctttggt tttgatgaac cacaactgct gaagtactac 5280 actatgcttg gcatgtgtaa gtggccagta gttgtttgtg gcaattattt tgctttcaag 5340 cagtcaaata ataattgcta catcaacgtg gcatgtttaa tgctgcaaca cttgagttta 5400 aagtttccta agtggcaatg gcaagaggct tggaacgagt tccgctctgg taaaccacta 5460 aggtttgtgt ccttggtatt agcaaagggc agctttaaat ttaatgaacc ttctgattct 5520 atcgatttta tgcgtgtggt gctacgtgaa gcagatttga gtggtgccac gtgcaatttg 5580 gaatttgttt gtaaatgtgg tgtgaagcaa gagcagcgca aaggtgttga cgctgttatg 5640 cattttggta cgttggataa aggtgatctt gtcaggggtt ataatatcgc atgtacgtgc 5700 ggtagtaaac ttgtgcattg cacccaattt aacgtaccat ttttaatttg ctccaacaca 5760 ccagagggta ggaaactgcc cgacgatgtt gttgcagcta atatttttac tggtggtagt 5820 gtgggccatt acacgcatgt gaaatgtaaa cccaagtacc agctttatga tgcttgtaat 5880 gttaataagg tttcggaggc taagggtaat tttaccgatt gcctctacct taaaaattta 5940 aagcaaacct tctcgtctgt gctgacgact ttttatttag atgacgtaaa gtgtgtggag 6000 tataagccag atttatcgca gtattactgt gagtctggta aatattatac aaaacccatt 6060 attaaggccc aatttagaac atttgagaag gttgatggtg tctataccaa ctttaaattg 6120 gtgggacata gtattgctga aaaactcaat gctaagctgg gatttgattg taattctccc 6180 tttgtggagt acaaaattac agagtggcca acagctactg gagatgtggt gttggctagt 6240 gatgatttgt atgtaagtcg gtacttaagc gggtgcatta cttttggtaa accggttgtc 6300 tggcttggcc atgaggaagc atcgctgaaa tctctcacat attttaatag acctagtgtc 6360 gtttgtgaaa ataaatttaa cgtgttgccc gttgatgtca gtgaacccac ggacaagggg 6420 cctgtgcctg ctgcagtcct tgttaccggc gtccctggag ctgatgcgtc agctggtgcc 6480 ggtattgcca aggagcaaaa agcctgtgct tctgctagtg tggaggatca ggttgttacg 6540 gaggttcgtc aagagccatc tgtttcagct gctgatgtca aagaggttaa attgaatggt 6600 gttaaaaagc ctgttaaggt ggaaggtagt gtggttgtta atgatcccac tagcgaaacc 6660 aaagttgtta aaagtttgtc tattgttgat gtctatgata tgttcctgac agggtgtaag 6720 tatgtggttt ggactgctaa tgagttgtct cgactagtaa attcaccgac tgttagggag 6780 tatgtgaagt ggggtatggg aaagattgta acacccgcta agttgttgtt gttaagagat 6840 gagaagcaag agttcgtagc gccaaaagta gtcaaggcga aagctattgc ctgctattgt 6900 gctgtgaagt ggtttctcct ctattgtttt agttggataa agtttaatac tgacaataag 6960 gttatataca ccacagaagt agcttcaaag cttactttca agttgtgctg tttggccttt 7020 aagaatgcct tacagacgtt taattggagc gttgtgtcta ggggcttttt cctagttgca 7080 acggtctttt tactctggtt taactttttg tatgctaatg ttattttgag tgacttctat 7140 ttgcctaata ttgggcctct ccctacgttt gtgggacaga tagttgcgtg gtttaagact 7200 acatttggtg tgtcaaccat ctgtgatttc taccaggtga cggatttggg ctatagaagt 7260 tcgttttgta atggaagtat ggtatgtgaa ctatgcttct caggttttga tatgctggac 7320 aactatgatg ctataaatgt tgttcaacac gttgtagata ggcgtttgtc ctttgactat 7380 attagcctat ttaaactggt agttgagctt gtaatcggct actctcttta tactgtgtgc 7440 ttctacccac tgtttgtcct tattggaatg cagttattga ccacatggtt gcctgaattc 7500 tttatgctgg agactatgca ttggagtgct cgtttgtttg tgtttgttgc caatatgctt 7560 ccagctttta cgttactgcg attttacatc gtggtgacag ctatgtataa ggtctattgt 7620 ctttgtagac atgttatgta tggatgtagt aagcctggtt gcttgttttg ttataagaga 7680 aaccgtagtg tccgtgttaa gtgtagcacc gttgttggtg gttcactacg ctattacgat 7740 gtaatggcta acggcggcac aggtttctgt acaaagcacc agtggaactg tcttaattgc 7800 aattcctgga aaccaggcaa tacattcata actcatgaag cagcggcgga cctctctaag 7860 gagttgaaac gccctgtgaa tccaacagat tctgcttatt actcggtcac agaggttaag 7920 caggttggtt gttccatgcg tttgttctac gagagagatg gacagcgtgt ttatgatgat 7980 gttaatgcta gtttgtttgt ggacatgaat ggtctgctgc attctaaagt taaaggtgtg 8040 cctgaaacgc atgttgtggt tgttgagaat gaagctgata aagctggttt tctcggcgcc 8100 gcagtgtttt atgcacaatc gctctacaga cctatgttga tggtggaaaa gaaattaata 8160 actaccgcca acactggttt gtctgttagt cgaactatgt ttgaccttta tgtagattca 8220 ttgctgaacg tcctcgacgt ggatcgcaag agtctaacaa gttttgtaaa tgctgcgcac 8280 aactctctaa aggagggtgt tcagcttgaa caagttatgg atacctttat tggctgtgcc 8340 cgacgtaagt gtgctataga ttctgatgtt gaaaccaagt ctattaccaa gtccgtcatg 8400 tcggcagtaa atgctggcgt tgattttacg gatgagagtt gtaataactt ggtgcctacc 8460 tatgttaaaa gtgacactat cgttgcagcc gatttgggtg ttcttattca gaataatgct 8520 aagcatgtac aggctaatgt tgctaaagcc gctaatgtgg cttgcatttg gtctgtggat 8580 gcttttaacc agctatctgc tgacttacag cataggctgc gaaaagcatg ttcaaaaact 8640 ggcttgaaga ttaagcttac ttataataag caggaggcaa atgttcctat tttaactaca 8700 ccgttctctc ttaaaggggg cgctgttttt agtagaatgt tacaatggtt gtttgttgct 8760 aatttgattt gtttcattgt gttgtgggcc cttatgccaa catatgcagt gcacaaatcg 8820 gatatgcagt tgcctttata tgccagtttt aaagttatag ataacggtgt gctaagggat 8880 gtgtctgtta ctgacgcatg cttcgcaaac aaatttaatc aattcgacca atggtatgag 8940 tctacttttg gtcttgctta ttaccgcaac tctaaggctt gtcctgttgt ggttgctgta 9000 atagatcaag acattggcca taccttattt aatgttccta ccacagtttt aagatatgga 9060 tttcatgtgt tgcattttat aacccatgca tttgctactg atagcgtgca gtgttacacg 9120 ccacatatgc aaatccccta tgataatttc tatgctagtg gttgcgtgtt gtcatccctc 9180 tgtactatgc ttgcgcatgc agatggaacc ccgcatcctt attgttatac agggggtgtt 9240 atgcataatg cctctctgta tagttctttg gctcctcatg tccgttataa cctggctagt 9300 tcaaatggtt atatacgttt tcccgaagtg gttagtgaag gcattgtgcg tgttgtgcgc 9360 actcgctcta tgacctactg cagggttggt ttatgtgagg aggccgagga gggtatctgc 9420 tttaatttta atcgttcatg ggtattgaac aacccgtatt atagggccat gcctggaact 9480 ttttgtggta ggaatgcttt tgatttaata catcaagttt taggaggatt agtgcggcct 9540 attgatttct ttgccttaac ggcgagttca gtggctggtg ctatccttgc aattattgtc 9600 gttttggctt tctattattt aatcaagctt aagcgtgcct ttggtgacta cactagtgtt 9660 gtggttatca atgtaattgt gtggtgtata aattttctga tgctttttgt gtttcaggtt 9720 tatcccacat tgtcttgttt atatgcttgt ttctacttct acaccacgct ttatttccct 9780 tcggagataa gtgttgttat gcatttgcaa tggcttgtca tgtatggtgc tattatgccc 9840 ttgtggtttt gcattattta cgtggcagtc gttgtttcaa accatgcatt gtggttgttc 9900 tcttactgcc gcaaaattgg taccgaggtt cgtagtgacg gcacatttga ggaaatggcc 9960 cttactacct ttatgattac taaagaatct tattgtaagt tgaaaaactc tgtttctgat 10020 gttgctttta acaggtactt gagtctttac aacaagtacc gttacttcag tggcaaaatg 10080 gatactgccg cttatagaga ggctgcctgt tcacaactgg caaaggcaat ggaaacattt 10140 aaccataata atggtaatga tgttctctat cagcctccaa ccgcctctgt tactacatca 10200 tttttacagt ctggtatagt gaagatggtg tcgcccacct ctaaagtgga gccttgtatt 10260 gttagtgtta cttatggtaa catgacactt aatgggttgt ggttggatga taaagtttat 10320 tgcccaagac atgttatctg ttcttcagct gacatgacag accctgatta tcctaatttg 10380 ctttgtagag tgacatcaag tgatttttgt gttatgtctg gtcgtatgag ccttactgta 10440 atgtcttatc aaatgcaggg ctgccaactt gttttgactg ttacactgca aaatcctaac 10500 acgcctaagt attccttcgg tgttgttaag cctggtgaga catttactgt actggctgca 10560 tacaatggca gacctcaagg agccttccat gttacgcttc gtagtagcca taccataaag 10620 ggctcctttc tatgtggatc ctgcggttct gtaggatatg ttttaactgg cgatagtgta 10680 cgatttgttt atatgcatca gctagagttg agtactggtt gtcataccgg tactgacttt 10740 agtgggaact tttatggtcc ctatagagat gcgcaagttg tacaattgcc tgttcaggat 10800 tatacgcaga ctgttaatgt tgtagcttgg ctttatgctg ctatttttaa cagatgcaac 10860 tggtttgtgc aaagtgatag ttgttccctg gaggagttta atgtttgggc tatgaccaat 10920 ggttttagct caatcaaagc cgatcttgtc ttggatgcgc ttgcttctat gacaggcgtt 10980 acagttgaac aggtgttggc cgctattaag aggctgcatt ctggattcca gggcaaacaa 11040 attttaggta gttgtgtgct tgaagatgag ctgacaccaa gtgatgttta tcaacaacta 11100 gctggtgtca agctacagtc aaagcgcaca agagttataa aaggtacatg ttgctggata 11160 ttggcttcaa cgtttttgtt ctgtagcatt atctcagcat ttgtaaaatg gactatgttt 11220 atgtatgtta ctacccatat gttgggagtg acattgtgtg cactttgttt tgtaagcttt 11280 gctatgttgt tgatcaagca taagcatttg tatttaacta tgtacatcat gcctgtgtta 11340 tgcacactgt tttacaccaa ctatttggtt gtgtacaaac agagttttag aggtctagct 11400 tatgcttggc tttcacactt tgtccctgct gtagattata catatatgga tgaagtttta 11460 tatggtgttg tgttgctagt agctatggtg tttgttacca tgcgtagcat aaaccacgac 11520 gtcttttcta ttatgttctt ggttggtaga cttgtcagcc tggtatccat gtggtatttt 11580 ggagccaatt tagaggaaga ggtactattg ttcctcacat ccctatttgg cacgtacaca 11640 tggactacta tgttgtcatt ggctaccgct aaggttattg ctaaatggtt ggctgtgaat 11700 gtcttgtact tcacagacgt accgcaaatt aaattagttc tgttgagcta cttgtgtatt 11760 ggttatgtgt gttgttgtta ttggggaatc ttgtcactcc ttaatagcat ttttaggatg 11820 ccattgggcg tctacaatta taaaatctcc gttcaggagt tacgttatat gaatgctaat 11880 ggcttgcgcc cacctagaaa tagttttgag gccctgatgc ttaattttaa gctgttggga 11940 attggtggtg tgccagtcat tgaagtatct caaattcaat caagattgac ggatgttaaa 12000 tgtgctaatg ttgtgttgct taattgcctc cagcacttgc atattgcatc taattctaag 12060 ttgtggcagt attgtagtac tttgcacaat gaaatactgg ctacatctga tttgagcgtg 12120 gccttcgata agttggctca actcttagtt gttttatttg ctaatccagc agcagtggat 12180 agcaagtgcc ttgcaagtat tgaagaagtg agcgatgatt acgttcgcga caatactgtc 12240 ttgcaagcct tacagagtga atttgttaat atggctagct tcgttgagta tgaacttgct 12300 aagaagaatc tagatgaggc taaggctagc ggctctgcca atcaacagca gattaagcag 12360 ctagagaagg cgtgtaatat tgctaagtca gcatatgagc gcgacagagc tgttgctcgt 12420 aagctggaac gtatggctga tttagctctt acaaacatgt ataaagaagc tagaattaat 12480 gataagaaga gtaaggtagt gtctgcattg caaaccatgc tctttagtat ggtgcgtaag 12540 ctagataacc aagctcttaa ttctatttta gacaacgcag ttaagggttg tgtacctttg 12600 aatgcaatac catcattgac ttcgaacact ctgactataa tagtgccaga taagcaggtt 12660 tttgatcagg ttgtggataa tgtgtatgtc acctatgctg ggaatgtatg gcatatacag 12720 tttattcaag atgctgatgg tgctgttaaa caattgaatg agatagatgt taattcaacc 12780 tggcctctag tcattgctgc aaataggcat aatgaagtgt ctactgttgt tttgcagaac 12840 aatgagttga tgcctcagaa gttgagaact caggttgtca atagtggctc agatatgaat 12900 tgtaatactc ctacccagtg ttactataat actactggca cgggtaagat tgtgtatgct 12960 atacttagtg actgtgacgg cctgaagtac actaagatag taaaagaaga tggaaattgt 13020 gttgttttgg aattggatcc tccctgtaag ttttctgttc aggatgtgaa gggccttaaa 13080 attaagtacc tttactttgt gaaggggtgt aatacactgg ctagaggctg ggttgtaggc 13140 accttatcct cgacagtgag attgcaggcg ggtacggcaa ctgagtatgc ctccaactct 13200 gcaatactgt cgctgtgtgc gttttctgta gatcctaaga aaacgtactt ggattatata 13260 aaacagggtg gagttcccgt tactaattgt gttaagatgt tatgtgacca tgctggcact 13320 ggtatggcca ttactattaa gccggaggca accactaatc aggattctta tggtggtgct 13380 tccgtttgta tatattgccg ctcgcgtgtt gaacatccag atgttgatgg attgtgcaaa 13440 ttacgcggca agtttgtcca agtgccctta ggcataaaag atcctgtgtc atatgtgttg 13500 acgcatgatg tttgtcaggt ttgtggcttt tggcgagatg gtagctgttc ctgtgtaggc 13560 acaggctccc agtttcagtc aaaagacacg aactttttaa acggattcgg ggtacaagtg 13620 taaatgcccg tcttgtaccc tgtgccagtg gcttggacac tgatgttcaa ttaagggcat 13680 ttgacatttg taatgctaat cgagctggca ttggtttgta ttataaagtg aattgctgcc 13740 gcttccagcg tgtagatgag gacggcaaca agttggataa gttctttgtt gttaaaagaa 13800 ctaatttaga agtgtataac aaggagaaag aatgctatga gttgacaaaa gaatgcggtg 13860 ttgtggctga acacgagttc ttcacatttg atgtggaggg aagtcgggta ccacacatag 13920 tccgtaaaga tctttcaaag tttactatgt tagatctttg ctatgcattg cgtcattttg 13980 accgcaatga ttgttcaact cttaaggaaa ttctccttac atatgctgag tgtgaagagt 14040 cctacttcca aaagaaggac tggtatgatt ttgttgagaa tcctgatata attaatgtgt 14100 acaagaagct tggtcctata tttaatagag ccctgcttaa cactgccaag tttgcagacg 14160 cattagtgga ggcaggctta gtaggtgttt taacacttga taatcaagat ttatatggtc 14220 aatggtatga ctttggagat tttgtcaaga cagtacctgg ttgtggtgtt gccgtggcag 14280 actcttatta ttcatatatg atgccaatgc tgactatgtg tcatgcgttg gatagtgagt 14340 tgtttgttaa tggtacttat agggagtttg accttgttca gtatgatttt actgatttca 14400 agctagagct gttcactaag tattttaagc attggagtat gacctaccac ccgaacacct 14460 gtgagtgcga ggatgacagg tgcattattc attgcgccaa ttttaatata cttttcagca 14520 tggtcttacc taagacctgt tttgggcctc ttgttaggca gatatttgtg gatggtgttc 14580 ctttcgttgt gtcgatcggt taccattata aagaattagg tgttgttatg aatatggatg 14640 tggatacaca tcgttatcgc ttgtctctta aggacttgct tttgtatgct gcagaccctg 14700 cccttcatgt ggcgtctgct agtgcactgc ttgatttgcg cacatgttgt tttagcgttg 14760 cagctattac aagtggcgta aaatttcaaa cagttaaacc tggaaatttt aatcaggatt 14820 tctacgagtt tattttgagt aaaggcctgc ttaaagaggg gagctccgtt gatttgaagc 14880 acttcttctt tacgcaggat ggtaatgctg ctattactga ttacaattac tacaagtata 14940 atctacccac catggtggat attaagcagt tgttgtttgt tttagaagtt gttaataagt 15000 acttcgagat ctatgagggt gggtgtatac ccgcaacaca ggtcattgtt aataattatg 15060 acaagagtgc tggctatcca tttaataaat ttggaaaggc caggctctat tatgaggcat 15120 tatcatttga ggagcaggat gaaatttatg cgtataccaa acgcaatgtc ctgccgaccc 15180 taactcaaat gaatcttaaa tatgctatta gtgctaagaa tagggcccgc accgttgctg 15240 gtgtctctat tctcagtact atgactggca gaatgtttca tcaaaagtgt ctaaagagta 15300 tagcagctac tcgcggtgtt cctgtagtta taggcaccac gaagttctat ggcggttggg 15360 atgatatgtt acgccgcctt attaaagatg ttgatagtcc tgtactcatg ggttgggact 15420 atcctaaatg tgatcgtgct atgccaaaca tactgcgtat tgttagtagt ttggtgctag 15480 cccgtaaaca tgattcgtgc tgttcgcata cggatagatt ctatcgtctt gcgaacgagt 15540 gcgcccaagt tttgagtgaa attgttatgt gtggtggttg ttattatgtt aaaccaggtg 15600 gcactagtag tggggatgca accactgctt ttgctaattc tgtgtttaac atttgtcaag 15660 ctgtttccgc caatgtatgc tcgcttatgg catgcaatgg acacaaaatt gaagatttga 15720 gtatacgcga gttacaaaag cgcctatact ctaatgtcta tcgtgcggac catgttgacc 15780 ccgcatttgt tagtgagtat tatgagtttt taaacaagca ttttagtatg atgattttga 15840 gtgatgatgg tgttgtgtgt tataattcag agtttgcgtc caagggttat attgctaata 15900 taagtgcctt tcaacaggta ttatattatc aaaacaacgt gtttatgtct gaggccaaat 15960 gttgggtaga aacagacatc gaaaagggac cgcatgaatt ttgttctcaa catacaatgc 16020 tagtcaagat ggatggtgat gaagtctacc ttccataccc tgatccttcg agaatcttag 16080 gagcaggctg ttttgttgat gatttactca agactgatag cgttctcttg atagagcgtt 16140 tcgtaagtct tgcaattgat gcttatcctt tagtatacca tgagaaccca gagtatcaaa 16200 atgtgttccg ggtatattta gaatacatca agaagctgta caatgatctc ggtaatcaga 16260 tcctggacag ctacagtgtt attttaagta cttgtgatgg tcaaaagttt actgacgaga 16320 cgttttacaa gaacatgtat ttaagaagtg cagtgctgca aagcgttggt gcctgcgttg 16380 tctgtagttc tcaaacatca ttacgttgtg gcagttgcat acgcaagcct ttgctgtgtt 16440 gcaaatgcgc ctatgatcat gttatgtcca ctgatcataa atatgtcctg agtgtgtcac 16500 catatgtgtg taattcaccg ggatgtgatg taaatgatgt taccaaattg tatttaggtg 16560 gtatgtcata ttattgtgag gaccataaac cacagtattc attcaaattg gtgatgaatg 16620 gtatggtttt tggtttatat aagcagtctt gtactggttc gccctacata gaggatttta 16680 ataaaatcgc tagttgcaaa tggacagaag tcgatgatta tgtgctagct aatgaatgca 16740 ccgaacgcct taaattgttt gccgcagaaa cgcagaaggc cacagaagag gcctttaagc 16800 aatgttatgc gtcagcaacg atccgtgaga tcgtgagcga tcgggagtta attttatctt 16860 gggaaattgg taaagtccgc ccgccactta ataaaaatta cgtgttcacc ggctaccatt 16920 ttactaataa tggtaagaca gttttaggtg agtatgtttt tgataagagt gagttgacta 16980 atggtgtgta ttatcgcgcc acaaccactt ataagttatc tgtaggtgat gtgttcattt 17040 taacatcaca cgcagtgtct agtttaagtg ctcctacatt agtaccgcag gagaattata 17100 ctagcattcg ttttgctagt gtttatagtg tgcctgagac gtttcagaat aatgtgccta 17160 attatcagca cattggaatg aagcgctatt gtactgtaca gggaccgcct ggtactggta 17220 agtcccatct agccattggg ctagctgttt attattgtac agcgcgcgtg gtgtataccg 17280 ctgctagcca tgctgcagtt gacgcgctgt gtgaaaaggc acataaattt ctcaacatca 17340 acgactgcac gcgtattgtt cctgcaaagg tgcgtgtaga ttgttatgat aaattcaagg 17400 tcaatgacac cactcgcaag tatgtgttta ctacaataaa tgcattacct gagttggtga 17460 ctgacattat tgtcgttgat gaagttagta tgcttaccaa ctatgagctg tctgttatta 17520 acagtcgtgt tagggctaag cattatgtgt atattggcga cccggcgcag ttacctgcac 17580 cacgtgtgct actgaataag ggaactctag aacctagata ttttaattcc gttaccaagc 17640 taatgtgttg tttgggtcca gatattttct tgggcacctg ttatagatgc cctaaggaga 17700 ttgtggatac ggtgtcagcc ttggtttata ataataagct gaaggctaaa aatgataata 17760 gctccatgtg ctttaaggtt tattataagg gccagactac acatgagagt tctagtgctg 17820 ttaatatgca gcaaatacat ttaatttcca agtttctgaa ggcaaacccc agttggagta 17880 acgccgtatt tattagtcct tataactcgc agaactatgt tgctaagaga gtcttgggat 17940 tacaaaccca gacagtagac tcagcgcagg gttctgaata tgattttgtt atctactcac 18000 agactgcgga aacagcgcat tctgtcaatg taaatagatt caatgttgct attacacgtg 18060 ctaagaaggg tattctctgt gtcatgagta gtatgcaatt atttgagtct cttaatttta 18120 ctacactgac gttggataag attaacaatc cacgattaca gtgtactaca aatttgttta 18180 aggattgtag caggagctat gtaggatatc acccagccca tgcaccatcc tttttggcag 18240 ttgatgacaa atataaggta ggcggtgatt tagccgtttg ccttaatgtt gctgattctg 18300 ctgtcactta ttcgcggctt atatcactca tgggattcaa gcttgacttg acccttgatg 18360 gttattgtaa gctgtttata actagagatg aagctatcaa acgtgttaga gcctgggttg 18420 gcttcgatgc agaaggtgcc catgcgatac gtgatagcat tgggacaaat ttcccattac 18480 aattaggctt ttcgactgga attgattttg ttgtcgaagc cactggaatg tttgctgaga 18540 gagatggtta tgtctttaaa aaggcagccg cacgagctcc tcctggcgaa caatttaaac 18600 accttatccc acttatgtca agagggcaga aatgggatgt ggttcgcatt agaatagtac 18660 aaatgttgtc agaccaccta gtggatttgg cagacagtgt tgtacttgtg acgtgggctg 18720 ccagctttga gctcacatgt ttgcgatatt tcgctaaagt tggaagagaa gttgtgtgta 18780 gtgtctgcac caagcgtgcg acatgtttta attctagaac tggatactat ggatgctggc 18840 gacatagtta ttcctgtgat tacctgtaca acccactaat agttgacatt caacagtggg 18900 gatatacagg atctttaact agcaatcatg atcctatttg cagcgtgcat aagggtgctc 18960 atgttgcatc atctgatgct atcatgaccc ggtgtctagc tgttcatgat tgcttttgta 19020 agtctgttaa ttggaattta gaatacccca ttatttcaaa tgaggtcagt gttaatacct 19080 cctgcaggtt attgcagcgc gtaatgttta gggctgcgat gctatgcaat aggtatgatg 19140 tgtgttatga cattggcaac cctaaaggtc ttgcctgtgt caaaggatat gattttaagt 19200 tctatgacgc ctcccctgtt gttaagtcgg tcaaacagtt tgtttacaaa tacgaggcac 19260 ataaagatca atttttagat ggtttgtgta tgttttggaa ctgcaatgtg gataagtatc 19320 cagcgaatgc agttgtgtgt aggtttgaca cgcgtgtgtt gaacaaatta aatctccctg 19380 gctgtaatgg tggcagtttg tatgttaaca aacatgcatt ccacaccagt ccctttaccc 19440 gggctgcctt cgagaatttg aagcctatgc ctttctttta ttattcagat acgccctgtg 19500 tgtatatgga aggcatggaa tctaagcagg tcgattatgt cccattgaga agcgctacat 19560 gcatcacaag atgcaattta ggtggcgctg tttgtttaaa acatgctgag gagtatcgtg 19620 agtaccttga gtcttacaat acggcaacca cagcgggttt tactttttgg gtctataaga 19680 cttttgattt ttacaacctt tggaatactt ttactaggct ccaaagttta gaaaatgtag 19740 tgtataacct ggtcaacgct ggacactttg atggccgggc gggtgaactg ccttgtgctg 19800 ttataggtga gaaagtcatt gccaagattc aaaatgagga tgtcgtggtc tttaaaaata 19860 acacgccatt ccccactaat gtggctgtcg aattatttgc taagcgcagt attcggcccc 19920 accccgagct taagctcttt agaaatttga atattgacgt gtgctggagt cacgtccttt 19980 gggattatgc taaggatagt gtgttttgca gttcgacgta taaggtctgc aaatacacag 20040 atttacagtg cattgaaagc ttgaatgtac tttttgatgg tcgtgataat ggtgctcttg 20100 aagcttttaa gaagtgccgg aatggcgtct acattaacac gacaaaaatt aaaagtctgt 20160 cgatgattaa aggcccacaa cgtgccgatt tgaatggcgt agttgtggag aaagttggag 20220 attctgatgt ggaattttgg tttgctgtgc gtaaagacgg tgacgatgtt atcttcagcc 20280 gtacagggag ccttgaaccg agccattacc ggagcccaca aggtaatccg ggtggtaatc 20340 gcgtgggtga tctcagcggt aatgaagctc tagcgcgtgg cactatcttt actcaaagca 20400 gattattatc ttctttcaca cctcgatcag agatggagaa agattttatg gatttagatg 20460 atgatgtgtt cattgcaaaa tatagtttac aggactacgc gtttgaacac gttgtttatg 20520 gtagttttaa ccagaagatt attggaggtt tgcatttgct tattggctta gcccgtaggc 20580 agcaaaaatc caatctggta attcaagagt tcgtgacata cgactctagc attcattcgt 20640 actttatcac tgacgagaac agtggtagta gtaagagtgt gtgcactgtt attgatttat 20700 tgttagatga ttttgtggac attgtaaagt ccctgaatct aaagtgtgtg agtaaggttg 20760 ttaatgttaa tgtggatttt aaggacttcc agtttatgtt gtggtgcaat gaggagaagg 20820 tcatgacttt ctatcctcgt ttgcaggctg ctgctgactg gaaacctggt tatgttatgc 20880 ctgtcttata taagtatttg gaatcgcctc tggaaagagt aaacctctgg aattatggca 20940 agccgattac tttacctaca ggatgtatga tgaatgttgc taagtatact caattatgtc 21000 aatatttgag cactacaaca ttagcagttc cggctaatat gcgtgtctta caccttggtg 21060 ccggttcgga taagggtgtt gcccctgggt ctgcagttct taggcagtgg ctaccagcgg 21120 gaagtattct tgtagataat gatgtgaatc catttgtgag tgacagtgtc gcctcatatt 21180 atggaaattg tataacctta ccctttgatt gtcagtggga tctgataatt tctgatatgt 21240 acgaccctct tactaagaac attggggagt acaacgtgag taaagatgga ttctttactt 21300 acctctgtca tttaattcgt gacaagttgg ctctgggtgg cagtgttgcc ataaaaataa 21360 cagagttttc ttggaacgct gagttatata gtttaatggg gaagtttgcg ttctggacaa 21420 tcttttgcac caacgtaaac gcctcttcaa gtgaaggatt tttgattggc ataaattggt 21480 tgaataagac ccgtaccgaa attgacggta aaaccatgca tgccaattat ctgttttgga 21540 gaaatagtac aatgtggaat ggaggggctt acagtctctt tgacatgagt aagttccctt 21600 tgaaagcggc tggtacggct gttgttagcc ttaaaccaga ccaaataaat gacttagtcc 21660 tctccttgat tgagaagggc aagttattag tgcgtgatac acgcaaagaa gtttttgttg 21720 gcgatagcct agtaaatgtc aaataaacga acaatgtttg tttttcttgt tttattgcca 21780 ctagtctcta gtcagtgtgt taatcttaca accagaactc aattaccccc tgcatacact 21840 aattctttca cacgtggtgt ttattaccct gacaaagttt tcagatcctc agttttacat 21900 tcaactcagg acttgttctt acctttcttt tccaatgtta cttggttcca tgctatacat 21960 gtctctggga ccaatggtac taagaggttt gataaccctg tcctaccatt taatgatggt 22020 gtttactttg cttccactga gaagtctaac ataataagag gctggatttt tggtactact 22080 ttagattcga aaacccagtc cctacttatt gttaataacg ctactaatgt tgttatcaaa 22140 gtctgtgaat ttcaattttg taacgatcca tttttgggtg tttattacca caaaaacaac 22200 aaaagttgga tggaaagtga gttcagagtt tattctagtg cgaataattg cacttttgaa 22260 tacgtctctc agccttttct tatggacctt gaaggaaaac agggtaattt caaaaatctt 22320 agggaatttg tgttcaagaa tattgatggt tacttcaaga tatactctaa gcacacgcct 22380 attaatttag tgcgtgatct ccctcagggt ttttcggctt tagaaccatt ggtagatttg 22440 ccaataggta ttaacatcac taggtttcaa actttacttg ctttacatag aagttattta 22500 actcctggtg attcttcttc aggttggaca gctggtgctg cagcttatta tgtgggttat 22560 cttcaaccta ggacttttct actgaagtac aatgaaaatg gaaccattac agatgctgta 22620 gactgtgcac ttgaccctct ctcagaaaca aagtgtacgt tgaaatcctt cactgtagaa 22680 aaaggaatct atcaaacttc taactttaga gtccaaccaa cagaatctat tgttagattt 22740 cctaacatca caaacttgtg cccttttggt gaagttttta acgccaccag atttgcatct 22800 gtttatgctt ggaacaggaa gagaatcagc aactgtgttg ctgattattc tgtcctgtat 22860 aattccgcat cattttccac ttttaagtgt tatggagtgt ctcctactaa attaaatgat 22920 ctctgcttta ctaatgtcta tgcagattca tttgtaatta gaggtgatga agtcagacaa 22980 atcgctccag ggcaaactgg aaagattgct gattataact acaaattacc agatgatttt 23040 acaggctgcg ttatagcttg gaattctaac aatcttgatt ctaaggttgg tggtaattat 23100 aattacctgt acagattgtt taggaagtct aatctcaaac cttttgagag agatatttca 23160 actgaaatct atcaggccgg tagcacacct tgtaatggtg ttgaaggttt taattgttac 23220 tttcctctgc aatcatatgg tttccaaccc actaatggtg ttggttacca accatacaga 23280 gtagtagtac tttcttttga acttctacat gcaccagcaa ctgtttgtgg acctaaaaag 23340 tctactaatt tggttaagaa caagtgtgtc aatttcaact tcaatggttt aacaggcaca 23400 ggtgttctta ctgagtctaa caaaaagttt ctgcctttcc aacaatttgg cagagacatt 23460 gctgacacta ctgatgctgt tcgtgatcca caaacacttg agattcttga cattacacca 23520 tgttcttttg gtggtgtcag tgttataaca ccaggaacaa atacttctaa ccaggttgct 23580 gttctttatc aggatgttaa ctgcacagaa gtccctgttg ctattcatgc agatcaactt 23640 actcctactt ggcgtgttta ttctacaggt tctaatgttt ttcaaacacg tgcaggctgt 23700 ttaatagggg ctgaacatgt caacaactca tatgagtgtg acatacccat tggtgcaggt 23760 atatgcgcta gttatcagac tcagactaat tctcctcgga gagcaagaag tgtagctagt 23820 caatccatca ttgcctacac tatgtcactt ggtgcagaaa attcagttgc ttactctaat 23880 aactctattg ccatacccac aaattttact attagcgtta ccacagaaat tctaccagtg 23940 tctatgacca agacatcagt agattgtaca atgtacattt gtggtgattc aactgaatgc 24000 agcaatcttt tgttgcaata tggcagtttt tgtacacaat taaaccgtgc tttaactgga 24060 atagctgttg aacaagacaa aaacacccaa gaagtttttg cacaagtcaa acaaatttac 24120 aagacaccac caattaaaga ttttggcggt tttaatttta gccagatact gccagatcca 24180 tcaaaaccaa gcaagaggtc atttattgaa gatctactgt tcaacaaagt gacacttgca 24240 gatgctggct tcatcaaaca atatggtgat tgccttggtg atattgctgc tagagacctc 24300 atttgtgcac aaaagtttaa cggccttact gttttgccac ctttgctcac agatgaaatg 24360 attgctcaat acacttctgc actgttagca ggtacaatca cttctggttg gacttttggt 24420 gcaggtgctg cattacaaat accatttgct atgcaaatgg cttataggtt taatggtatt 24480 ggagttacac agaatgttct ctatgagaac caaaaattga ttgccaacca atttaatagt 24540 gctattggca aaattcaaga ctcactttct tccacagcaa gtgcacttgg aaaacttcaa 24600 gatgtggtca accaaaatgc acaagcttta aacacgcttg ttaaacaact tagctccaat 24660 tttggtgcaa tttcaagtgt tttaaacgac atcctttcac gtcttgacaa agttgaggct 24720 gaagtgcaaa ttgataggtt gatcacaggc agacttcaaa gtttgcagac atatgtgact 24780 caacaattaa ttagagctgc agaaatcaga gcttctgcta atcttgctgc tactaaaatg 24840 tcagagtgtg tacttggaca atcaaaaaga gttgactttt gcggaaaggg ctatcatctt 24900 atgtcatttc ctcagtcagc acctcatggt gtcgtctttt tgcatgtgac ttatgtccct 24960 gcacaagaaa agaacttcac aactgctcct gccatttgtc atgatggaaa agcacacttt 25020 cctcgtgaag gtgtctttgt ttcaaatggc acacactggt ttgtaacaca aaggaatttt 25080 tatgaaccac aaatcattac tacagacaac acatttgtgt ctggtaactg tgatgttgta 25140 ataggaattg tcaacaacac agtttatgat cctttgcaac ctgaattaga ctcattcaag 25200 gaggagcttg ataaatactt caagaaccat acctcaccag atgttgattt aggtgacatc 25260 tctggcatta atgcttcagt tgtaaacatt cagaaagaaa tcgaccgcct caatgaggtt 25320 gccaagaatt taaatgaatc tctcatcgat ctccaagaac ttggaaagta tgagcagtat 25380 ataaaatggc catggtacat ttggctaggt tttatagctg gcttgattgc catagtaatg 25440 gtgacaatta tgctttgctg tatgaccagt tgctgtagtt gtctcaaggg ctgttgttct 25500 tgtggatcct gctgcaaatt tgacgaggac gactctgagc cagtgctcaa aggagtcaaa 25560 ttacattaca cataactatc acagcctctc ctggaaagac agaaaatcta aacaatttat 25620 agcattctca ttgctacctg gccccgtaag aggcagtcat agctatggcc gtgttggtcc 25680 taaggctaca ttggctgctg tctttattgg tccatttatt gtagcatgta tgctaggcat 25740 tggcctagtt tatttattgc aattgcaagt tcaaattttt catgttaagg ataccatacg 25800 tgtgactggc aagccagcca ctgtgtctta tactacaagt acaccagtaa caccgagcgc 25860 gacgacgctc gatggtacta cgtatacttt aattagaccc actagctctt atacaagagt 25920 ttatcttggt actccaagag gttttgatta tagtacattt gggcctaaga ccctagatta 25980 tgttactaat ctaaacctca tcttaattct ggtcgtccat atacttttaa ggcattgtcc 26040 aggcatatga ggccaacagc cacatggatt tggcatgtga gtgatgcatg gttacgccgc 26100 acgcgggact ttggtgtcat tcgcctagaa gatttttgtt ttcaatttaa ttatagccaa 26160 ccccgagttg gttattgtag agttccttta aaggcttggt gtagcaacca gggtaaattt 26220 gcagcgcagt ttaccctaaa aagttgcgaa aaaccaggtc acgaaaaatt tattactagc 26280 ttcacggcct acggcagaac tgtccaacag gccgttagca agttagtaga agaagctgtt 26340 gattttattc tttttagggc cacgcagctc gaaagaaatg tttaatttat tccttacaga 26400 cacagtatgg tatgtggggc agattatttt tatattcgca gtgtgtttga tggtcaccat 26460 aattgtggtt gccttccttg cgtctatcaa actttgtatt caactttgcg gtttatgtaa 26520 tactttggtg ctgtcccctt ctatttattt gtatgatagg agtaagcagc tttataagta 26580 ctataatgaa gaaatgagac tgcccctatt agaggtggat gatatctaat ccaaacatta 26640 tgagtagtac tactcaggcc ccagagcccg tctatcaatg gaccgccgac gaggcagttc 26700 aattccttaa ggaatggaac ttctcgttgg gcattatact actctttatt actatcatac 26760 tacagttcgg ttacacgagc cgtagcatgt ttatttatgt tgtgaaaatg ataatcttgt 26820 ggttaatgtg gccactgact attgttttgt gtattttcaa ttgcgtgtat gcgctaaata 26880 atgtgtatct tggattttct atagtgttta ctatagtgtc cattgtaatc tggatcatgt 26940 attttgtgaa cagcataagg ttgtttatca ggactggtag ctggtggagc ttcaaccccg 27000 aaacaaacaa ccttatgtgt atagatatga aaggtaccgt gtatgttaga cccattattg 27060 aggattacca tacactaaca gccactatta ttcgtggcca cctctacatg caaggtgtta 27120 agctaggcac cggtttctct ttgtctgact tgcccgctta tgttacagtt gctaaggtgt 27180 cacacctttg cacttataag cgcgcattct tagacaaggt agacggtgtt agcggttttg 27240 ctgtttatgt gaagtccaag gtcggaaatt accgactgcc ctcaaacaaa ccgagtggcg 27300 cggacaccgc attgttgaga acctaatcta aactttaagg agagaatgaa tcctatgtcg 27360 gcgctcggtg gtaacccctc gcgagaaagt cgggatagga cactctctat cagaatggat 27420 gtcttgctgt cataacagat agagaaggtt gtggcagacc ctgtatcaat tagttgaaag 27480 agattgcaaa atagagaatg tgtgagagaa gttagcaagg tcctacgtct aaccataaga 27540 acggcgatag gcgccccctg ggaacagctc acatcagggt actattcctg caatgcccta 27600 gtaaatgaat gaagttgatc atggccaatt ggaagaatca caaaaaaaaa aaaaaaaaaa 27660 acggccggtt t 27671 <210> 35 <211> 7341 <212> DNA <213> Artificial Sequence <220> <223> pcDNA34_syn_N <400> 35 agtacttaat acgactcact ataggctagc cgccaccatg gtgtctgata atggacctca 60 aaatcagcga aatgcacctc gcattacgtt tggtggacca tcagattcaa ctggcagtaa 120 ccagaatgga gaacgaagtg gtgcgcgatc aaaacaacgc cgcccgcaag gtttacccaa 180 taatactgcg tcttggttca ccgctctcac tcaacatggc aaggaagatt taaaattccc 240 tcgaggacaa ggcgttccaa ttaacaccaa tagcagtcca gatgaccaaa ttggctacta 300 ccgccgcgcc acaagacgaa ttcgtggtgg tgatggtaaa atgaaagatc tcagtccaag 360 atggtatttc tactatctag gaactgggcc agaagctgga cttccttatg gtgctaacaa 420 agatggcatc atatgggttg caactgaggg agccttgaat acaccaaaag atcacattgg 480 caccagaaat cctgctaaca atgctgcaat cgtgctacaa cttcctcaag gaacaacatt 540 accaaaaggt ttttacgcag aagggtctag aggtggaagt caagcctctt ctagatcatc 600 atcacgtagt cgcaacagtt caagaaattc aactccaggt tcaagtagag gaacttctcc 660 tgctagaatg gctggaaatg gaggtgatgc tgctcttgct ttgttactac ttgacagatt 720 gaaccagctt gagagcaaaa tgtctggtaa aggccaacaa caacaaggcc aaactgtcac 780 taagaaatct gctgctgagg cttctaagaa gcctagacaa aaacgtactg ccactaaagc 840 atacaatgta acacaagctt tcggcagacg tggtccagaa caaactcaag gaaattttgg 900 ggatcaggaa ctaatcagac aaggaactga ttacaaacat tggccgcaaa ttgcacaatt 960 tgctccttct gcttcagcgt tctttggaat gtcgagaatt ggaatggaag tcacaccttc 1020 gggaacatgg ttgacctata caggtgccat caaattggat gacaaagatc caaatttcaa 1080 agatcaagtc attttgctga ataagcatat tgacgcatac aaaacattcc caccaacaga 1140 gcctaaaaag gacaaaaaga agaaggctga tgaaactcaa gccttaccgc agagacagaa 1200 gaaacagcaa actgtgactc ttcttcctgc tgcagatttg gatgatttct ccaaacaatt 1260 gcaacaatcc atgagcagtg ctgactcaac tcaggcctaa gcggccgctt cgagcagaca 1320 tgataagata aagggttcga tccctaccgg ttagtaatga gtttgatatc tcgacaatca 1380 acctctggat tacaaaattt gtgaaagatt gactggtatt cttaactatg ttgctccttt 1440 tacgctatgt ggatacgctg ctttaatgcc tttgtatcat gctattgctt cccgtatggc 1500 tttcattttc tcctccttgt ataaatcctg gttgctgtct ctttatgagg agttgtggcc 1560 cgttgtcagg caacgtggcg tggtgtgcac tgtgtttgct gacgcaaccc ccactggttg 1620 gggcattgcc accacctgtc agctcctttc cgggactttc gctttccccc tccctattgc 1680 cacggcggaa ctcatcgccg cctgccttgc ccgctgctgg acaggggctc ggctgttggg 1740 cactgacaat tccgtggtgt tgtcggggaa gctgacgtcc tttccatggc tgctcgcctg 1800 tgttgccacc tggattctgc gcgggacgtc cttctgctac gtcccttcgg ccctcaatcc 1860 agcggacctt ccttcccgcg gcctgctgcc ggctctgcgg cctcttccgc gtcttcgcct 1920 tcgccctcag acgagtcgga tctccctttg ggccgcctcc ccgcctggaa acgggggagg 1980 ctaactgaaa cacggaagga gacaataccg gaaggaaccc gcgctatgac ggcaataaaa 2040 agacagaata aaacgcacgg gtgttgggtc gtttgttcat aaacgcgggg ttcggtccca 2100 gggctggcac tctgtcgata ccccaccgag accccattgg ggccaatacg cccgcgtttc 2160 ttccttttcc ccaccccacc ccccaagttc gggtgaaggc ccagggctcg cagccaacgt 2220 cggggcggca ggccctgcca tagcagatct gcgcagctgg ggctctaggg ggtatcccca 2280 cgcgccctgt agcggcgcat taagcgcggc gggtgtggtg gttacgcgca gcgtgaccgc 2340 tacacttgcc agcgccctag cgcccgctcc tttcgctttc ttcccttcct ttctcgccac 2400 gttcgccggc tttccccgtc aagctctaaa tcggggcatc cctttagggt tccgatttag 2460 tgctttacgg cacctcgacc ccaaaaaact tgattagggt gatggttcac gtagtgggcc 2520 atcgccctga tagacggttt ttcgcccttt gacgttggag tccacgttct ttaatagtgg 2580 actcttgttc caaactggaa caacactcaa ccctatctcg gtctattctt ttgatttata 2640 agggattttg gggatttcgg cctattggtt aaaaaatgag ctgatttaac aaaaatttaa 2700 cgcgaattaa ttctgtggaa tgtgtgtcag ttagggtgtg gaaagtcccc aggctcccca 2760 gcaggcagaa gtatgcaaag catgcatctc aattagtcag caaccaggtg tggaaagtcc 2820 ccaggctccc cagcaggcag aagtatgcaa agcatgcatc tcaattagtc agcaaccata 2880 gtcccgcccc taactccgcc catcccgccc ctaactccgc ccagttccgc ccattctccg 2940 ccccatggct gactaatttt ttttatttat gcagaggccg aggccgcctc tgcctctgag 3000 ctattccaga agtagtgagg aggctttttt ggaggcctag gcttttgcaa aaagctcccg 3060 ggagcttgta tatccatttt cggatctgat caagagacag gatgaggatc gtttcgcatg 3120 attgaacaag atggattgca cgcaggttct ccggccgctt gggtggagag gctattcggc 3180 tatgactggg cacaacagac aatcggctgc tctgatgccg ccgtgttccg gctgtcagcg 3240 caggggcgcc cggttctttt tgtcaagacc gacctgtccg gtgccctgaa tgaactgcag 3300 gacgaggcag cgcggctatc gtggctggcc acgacgggcg ttccttgcgc agctgtgctc 3360 gacgttgtca ctgaagcggg aagggactgg ctgctattgg gcgaagtgcc ggggcaggat 3420 ctcctgtcat ctcaccttgc tcctgccgag aaagtatcca tcatggctga tgcaatgcgg 3480 cggctgcata cgcttgatcc ggctacctgc ccattcgacc accaagcgaa acatcgcatc 3540 gagcgagcac gtactcggat ggaagccggt cttgtcgatc aggatgatct ggacgaagag 3600 catcaggggc tcgcgccagc cgaactgttc gccaggctca aggcgcgcat gcccgacggc 3660 gaggatctcg tcgtgaccca tggcgatgcc tgcttgccga atatcatggt ggaaaatggc 3720 cgcttttctg gattcatcga ctgtggccgg ctgggtgtgg cggaccgcta tcaggacata 3780 gcgttggcta cccgtgatat tgctgaagag cttggcggcg aatgggctga ccgcttcctc 3840 gtgctttacg gtatcgccgc tcccgattcg cagcgcatcg ccttctatcg ccttcttgac 3900 gagttcttct gagcgggact ctggggttcg cgaaatgacc gaccaagcga cgcccaacct 3960 gccatcacga gatttcgatt ccaccgccgc cttctatgaa aggttgggct tcggaatcgt 4020 tttccgggac gccggctgga tgatcctcca gcgcggggat ctcatgctgg agttcttcgc 4080 ccaccccaac ttgtttattg cagcttataa tggttacaaa taaagcaata gcatcacaaa 4140 tttcacaaat aaagcatttt tttcactgca ttctagttgt ggtttgtcca aactcatcaa 4200 tgtatcttat catgtctgta taccgtcgac ctctagctag agcttggcgt aatcatggtc 4260 atagctgttt cctgtgtgaa attgttatcc gctcacaatt ccacacaaca tacgagccgg 4320 aagcataaag tgtaaagcct ggggtgccta atgagtgagc taactcacat taattgcgtt 4380 gcgctcactg cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt aatgaatcgg 4440 ccaacgcgcg gggagaggcg gtttgcgtat tgggcgctct tccgcttcct cgctcactga 4500 ctcgctgcgc tcggtcgttc ggctgcggcg agcggtatca gctcactcaa aggcggtaat 4560 acggttatcc acagaatcag gggataacgc aggaaagaac atgtgagcaa aaggccagca 4620 aaaggccagg aaccgtaaaa aggccgcgtt gctggcgttt ttccataggc tccgcccccc 4680 tgacgagcat cacaaaaatc gacgctcaag tcagaggtgg cgaaacccga caggactata 4740 aagataccag gcgtttcccc ctggaagctc cctcgtgcgc tctcctgttc cgaccctgcc 4800 gcttaccgga tacctgtccg cctttctccc ttcgggaagc gtggcgcttt ctcaatgctc 4860 acgctgtagg tatctcagtt cggtgtaggt cgttcgctcc aagctgggct gtgtgcacga 4920 accccccgtt cagcccgacc gctgcgcctt atccggtaac tatcgtcttg agtccaaccc 4980 ggtaagacac gacttatcgc cactggcagc agccactggt aacaggatta gcagagcgag 5040 gtatgtaggc ggtgctacag agttcttgaa gtggtggcct aactacggct acactagaag 5100 gacagtattt ggtatctgcg ctctgctgaa gccagttacc ttcggaaaaa gagttggtag 5160 ctcttgatcc ggcaaacaaa ccaccgctgg tagcggtggt ttttttgttt gcaagcagca 5220 gattacgcgc agaaaaaaag gatctcaaga agatcctttg atcttttcta cggggtctga 5280 cgctcagtgg aacgaaaact cacgttaagg gattttggtc atgagattat caaaaaggat 5340 cttcacctag atccttttaa attaaaaatg aagttttaaa tcaatctaaa gtatatatga 5400 gtaaacttgg tctgacagtt accaatgctt aatcagtgag gcacctatct cagcgatctg 5460 tctatttcgt tcatccatag ttgcctgact ccccgtcgtg tagataacta cgatacggga 5520 gggcttacca tctggcccca gtgctgcaat gataccgcga gacccacgct caccggctcc 5580 agatttatca gcaataaacc agccagccgg aagggccgag cgcagaagtg gtcctgcaac 5640 tttatccgcc tccatccagt ctattaattg ttgccgggaa gctagagtaa gtagttcgcc 5700 agttaatagt ttgcgcaacg ttgttgccat tgctacaggc atcgtggtgt cacgctcgtc 5760 gtttggtatg gcttcattca gctccggttc ccaacgatca aggcgagtta catgatcccc 5820 catgttgtgc aaaaaagcgg ttagctcctt cggtcctccg atcgttgtca gaagtaagtt 5880 ggccgcagtg ttatcactca tggttatggc agcactgcat aattctctta ctgtcatgcc 5940 atccgtaaga tgcttttctg tgactggtga gtactcaacc aagtcattct gagaatagtg 6000 tatgcggcga ccgagttgct cttgcccggc gtcaatacgg gataataccg cgccacatag 6060 cagaacttta aaagtgctca tcattggaaa acgttcttcg gggcgaaaac tctcaaggat 6120 cttaccgctg ttgagatcca gttcgatgta acccactcgt gcacccaact gatcttcagc 6180 atcttttact ttcaccagcg tttctgggtg agcaaaaaca ggaaggcaaa atgccgcaaa 6240 aaagggaata agggcgacac ggaaatgttg aatactcata ctcttccttt ttcaatatta 6300 ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 6360 aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtcgacgg 6420 atcgggagat ctcccgatcc cctatggtcg actctcagta caatctgctc tgatgccgca 6480 tagttaagcc agtatctgct ccctgcttgt gtgttggagg tcgctgagta gtgcgcgagc 6540 aaaatttaag ctacaacaag gcaaggcttg accgacaatt gcatgaagaa tctgcttagg 6600 gttaggcgtt ttgcgctgct tcgcgatgta cgggccagat atacgcgttg acattgatta 6660 ttgactagtt attaatagta atcaattacg gggtcattag ttcatagccc atatatggag 6720 ttccgcgtta cataacttac ggtaaatggc ccgcctggct gaccgcccaa cgacccccgc 6780 ccattgacgt caataatgac gtatgttccc atagtaacgc caatagggac tttccattga 6840 cgtcaatggg tggagtattt acggtaaact gcccacttgg cagtacatca agtgtatcat 6900 atgccaagta cgccccctat tgacgtcaat gacggtaaat ggcccgcctg gcattatgcc 6960 cagtacatga ccttatggga ctttcctact tggcagtaca tctacgtatt agtcatcgct 7020 attaccatgg tgatgcggtt ttggcagtac atcaatgggc gtggatagcg gtttgactca 7080 cggggatttc caagtctcca ccccattgac gtcaatggga gtttgttttg gcaccaaaat 7140 caacgggact ttccaaaatg tcgtaacaac tccgccccat tgacgcaaat gggcggtagg 7200 cgtgtacggt gggaggtcta tataagcaga gctcgtttag tgaaccgtca gatcgcctgg 7260 agacgccatc cacgctgttt tgacctccat agaagacacc gggaccgatc cagcctccgg 7320 actctagagg atcgaaccct t 7341 <210> 36 <211> 6309 <212> DNA <213> Artificial Sequence <220> <223> pcDNA34_syn_E <400> 36 agtacttaat acgactcact ataggctagc cgccaccatg gtgtactcat tcgtttcgga 60 agagacaggt acgttaatag ttaatagcgt acttcttttt cttgctttcg tggtattctt 120 gctagttaca ctagccattc ttactgcgct tcgattgtgt gcgtactgtt gcaatattgt 180 taacgtgagt cttgtaaaac cttcttttta cgtttactct cgtgttaaaa atctgaattc 240 ttctcgggtt cctgatcttc tggtctaagc ggccgcttcg agcagacatg ataagataaa 300 gggttcgatc cctaccggtt agtaatgagt ttgatatctc gacaatcaac ctctggatta 360 caaaatttgt gaaagattga ctggtattct taactatgtt gctcctttta cgctatgtgg 420 atacgctgct ttaatgcctt tgtatcatgc tattgcttcc cgtatggctt tcattttctc 480 ctccttgtat aaatcctggt tgctgtctct ttatgaggag ttgtggcccg ttgtcaggca 540 acgtggcgtg gtgtgcactg tgtttgctga cgcaaccccc actggttggg gcattgccac 600 cacctgtcag ctcctttccg ggactttcgc tttccccctc cctattgcca cggcggaact 660 catcgccgcc tgccttgccc gctgctggac aggggctcgg ctgttgggca ctgacaattc 720 cgtggtgttg tcggggaagc tgacgtcctt tccatggctg ctcgcctgtg ttgccacctg 780 gattctgcgc gggacgtcct tctgctacgt cccttcggcc ctcaatccag cggaccttcc 840 ttcccgcggc ctgctgccgg ctctgcggcc tcttccgcgt cttcgccttc gccctcagac 900 gagtcggatc tccctttggg ccgcctcccc gcctggaaac gggggaggct aactgaaaca 960 cggaaggaga caataccgga aggaacccgc gctatgacgg caataaaaag acagaataaa 1020 acgcacgggt gttgggtcgt ttgttcataa acgcggggtt cggtcccagg gctggcactc 1080 tgtcgatacc ccaccgagac cccattgggg ccaatacgcc cgcgtttctt ccttttcccc 1140 accccacccc ccaagttcgg gtgaaggccc agggctcgca gccaacgtcg gggcggcagg 1200 ccctgccata gcagatctgc gcagctgggg ctctaggggg tatccccacg cgccctgtag 1260 cggcgcatta agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag 1320 cgccctagcg cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt 1380 tccccgtcaa gctctaaatc ggggcatccc tttagggttc cgatttagtg ctttacggca 1440 cctcgacccc aaaaaacttg attagggtga tggttcacgt agtgggccat cgccctgata 1500 gacggttttt cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca 1560 aactggaaca acactcaacc ctatctcggt ctattctttt gatttataag ggattttggg 1620 gatttcggcc tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattaatt 1680 ctgtggaatg tgtgtcagtt agggtgtgga aagtccccag gctccccagc aggcagaagt 1740 atgcaaagca tgcatctcaa ttagtcagca accaggtgtg gaaagtcccc aggctcccca 1800 gcaggcagaa gtatgcaaag catgcatctc aattagtcag caaccatagt cccgccccta 1860 actccgccca tcccgcccct aactccgccc agttccgccc attctccgcc ccatggctga 1920 ctaatttttt ttatttatgc agaggccgag gccgcctctg cctctgagct attccagaag 1980 tagtgaggag gcttttttgg aggcctaggc ttttgcaaaa agctcccggg agcttgtata 2040 tccattttcg gatctgatca agagacagga tgaggatcgt ttcgcatgat tgaacaagat 2100 ggattgcacg caggttctcc ggccgcttgg gtggagaggc tattcggcta tgactgggca 2160 caacagacaa tcggctgctc tgatgccgcc gtgttccggc tgtcagcgca ggggcgcccg 2220 gttctttttg tcaagaccga cctgtccggt gccctgaatg aactgcagga cgaggcagcg 2280 cggctatcgt ggctggccac gacgggcgtt ccttgcgcag ctgtgctcga cgttgtcact 2340 gaagcgggaa gggactggct gctattgggc gaagtgccgg ggcaggatct cctgtcatct 2400 caccttgctc ctgccgagaa agtatccatc atggctgatg caatgcggcg gctgcatacg 2460 cttgatccgg ctacctgccc attcgaccac caagcgaaac atcgcatcga gcgagcacgt 2520 actcggatgg aagccggtct tgtcgatcag gatgatctgg acgaagagca tcaggggctc 2580 gcgccagccg aactgttcgc caggctcaag gcgcgcatgc ccgacggcga ggatctcgtc 2640 gtgacccatg gcgatgcctg cttgccgaat atcatggtgg aaaatggccg cttttctgga 2700 ttcatcgact gtggccggct gggtgtggcg gaccgctatc aggacatagc gttggctacc 2760 cgtgatattg ctgaagagct tggcggcgaa tgggctgacc gcttcctcgt gctttacggt 2820 atcgccgctc ccgattcgca gcgcatcgcc ttctatcgcc ttcttgacga gttcttctga 2880 gcgggactct ggggttcgcg aaatgaccga ccaagcgacg cccaacctgc catcacgaga 2940 tttcgattcc accgccgcct tctatgaaag gttgggcttc ggaatcgttt tccgggacgc 3000 cggctggatg atcctccagc gcggggatct catgctggag ttcttcgccc accccaactt 3060 gtttattgca gcttataatg gttacaaata aagcaatagc atcacaaatt tcacaaataa 3120 agcatttttt tcactgcatt ctagttgtgg tttgtccaaa ctcatcaatg tatcttatca 3180 tgtctgtata ccgtcgacct ctagctagag cttggcgtaa tcatggtcat agctgtttcc 3240 tgtgtgaaat tgttatccgc tcacaattcc acacaacata cgagccggaa gcataaagtg 3300 taaagcctgg ggtgcctaat gagtgagcta actcacatta attgcgttgc gctcactgcc 3360 cgctttccag tcgggaaacc tgtcgtgcca gctgcattaa tgaatcggcc aacgcgcggg 3420 gagaggcggt ttgcgtattg ggcgctcttc cgcttcctcg ctcactgact cgctgcgctc 3480 ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag gcggtaatac ggttatccac 3540 agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa aggccaggaa 3600 ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg acgagcatca 3660 caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa gataccaggc 3720 gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc ttaccggata 3780 cctgtccgcc tttctccctt cgggaagcgt ggcgctttct caatgctcac gctgtaggta 3840 tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac cccccgttca 3900 gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg taagacacga 3960 cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt atgtaggcgg 4020 tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagga cagtatttgg 4080 tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct cttgatccgg 4140 caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag 4200 aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg ctcagtggaa 4260 cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct tcacctagat 4320 ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt aaacttggtc 4380 tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc tatttcgttc 4440 atccatagtt gcctgactcc ccgtcgtgta gataactacg atacgggagg gcttaccatc 4500 tggccccagt gctgcaatga taccgcgaga cccacgctca ccggctccag atttatcagc 4560 aataaaccag ccagccggaa gggccgagcg cagaagtggt cctgcaactt tatccgcctc 4620 catccagtct attaattgtt gccgggaagc tagagtaagt agttcgccag ttaatagttt 4680 gcgcaacgtt gttgccattg ctacaggcat cgtggtgtca cgctcgtcgt ttggtatggc 4740 ttcattcagc tccggttccc aacgatcaag gcgagttaca tgatccccca tgttgtgcaa 4800 aaaagcggtt agctccttcg gtcctccgat cgttgtcaga agtaagttgg ccgcagtgtt 4860 atcactcatg gttatggcag cactgcataa ttctcttact gtcatgccat ccgtaagatg 4920 cttttctgtg actggtgagt actcaaccaa gtcattctga gaatagtgta tgcggcgacc 4980 gagttgctct tgcccggcgt caatacggga taataccgcg ccacatagca gaactttaaa 5040 agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct taccgctgtt 5100 gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat cttttacttt 5160 caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa agggaataag 5220 ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt gaagcattta 5280 tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa ataaacaaat 5340 aggggttccg cgcacatttc cccgaaaagt gccacctgac gtcgacggat cgggagatct 5400 cccgatcccc tatggtcgac tctcagtaca atctgctctg atgccgcata gttaagccag 5460 tatctgctcc ctgcttgtgt gttggaggtc gctgagtagt gcgcgagcaa aatttaagct 5520 acaacaaggc aaggcttgac cgacaattgc atgaagaatc tgcttagggt taggcgtttt 5580 gcgctgcttc gcgatgtacg ggccagatat acgcgttgac attgattatt gactagttat 5640 taatagtaat caattacggg gtcattagtt catagcccat atatggagtt ccgcgttaca 5700 taacttacgg taaatggccc gcctggctga ccgcccaacg acccccgccc attgacgtca 5760 ataatgacgt atgttcccat agtaacgcca atagggactt tccattgacg tcaatgggtg 5820 gagtatttac ggtaaactgc ccacttggca gtacatcaag tgtatcatat gccaagtacg 5880 ccccctattg acgtcaatga cggtaaatgg cccgcctggc attatgccca gtacatgacc 5940 ttatgggact ttcctacttg gcagtacatc tacgtattag tcatcgctat taccatggtg 6000 atgcggtttt ggcagtacat caatgggcgt ggatagcggt ttgactcacg gggatttcca 6060 agtctccacc ccattgacgt caatgggagt ttgttttggc accaaaatca acgggacttt 6120 ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg gcggtaggcg tgtacggtgg 6180 gaggtctata taagcagagc tcgtttagtg aaccgtcaga tcgcctggag acgccatcca 6240 cgctgttttg acctccatag aagacaccgg gaccgatcca gcctccggac tctagaggat 6300 cgaaccctt 6309 <210> 37 <211> 6750 <212> DNA <213> Artificial Sequence <220> <223> pcDNA34_syn_M <400> 37 agtacttaat acgactcact ataggctagc cgccaccatg gtggcagatt ccaacggtac 60 tattaccgtt gaggagctga aaaagctcct tgaacaatgg aacctagtaa taggtttcct 120 attccttaca tggatttgcc tgctgcaatt tgcctatgcc aacaggaata ggtttttgta 180 catcattaag ttgattttcc tctggctgtt atggccagta actttagctt gttttgtgct 240 tgctgctgtt tacagaataa attggatcac cggtggaatt gctattgcaa tggcttgtct 300 tgtaggattg atgtggctaa gctacttcat tgcttctttc agactgtttg cgcgtacgcg 360 ttccatgtgg tcattcaatc cagaaactaa cattcttctc aacgtgccac tccatggaac 420 tattctgact agaccgcttc tagaaagtga actcgtaatc ggagctgtta tccttcgtgg 480 acatcttcgt attgctggac atcatctagg acgctgtgac atcaaggatc tacctaaaga 540 aatcactgtt gctacatcac gaacgctttc ttattacaaa ttgggagctt cacagcgtgt 600 agcaggtgat tcaggttttg ctgcatatag tcgctacagg attggcaact ataaattaaa 660 cacagaccat tccagtagca gtgacaatat tgctttgctt gtacagtaag cggccgcttc 720 gagcagacat gataagataa agggttcgat ccctaccggt tagtaatgag tttgatatct 780 cgacaatcaa cctctggatt acaaaatttg tgaaagattg actggtattc ttaactatgt 840 tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg ctattgcttc 900 ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc tttatgagga 960 gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg acgcaacccc 1020 cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg ctttccccct 1080 ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga caggggctcg 1140 gctgttgggc actgacaatt ccgtggtgtt gtcggggaag ctgacgtcct ttccatggct 1200 gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg tcccttcggc 1260 cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc ctcttccgcg 1320 tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc cgcctggaaa 1380 cgggggaggc taactgaaac acggaaggag acaataccgg aaggaacccg cgctatgacg 1440 gcaataaaaa gacagaataa aacgcacggg tgttgggtcg tttgttcata aacgcggggt 1500 tcggtcccag ggctggcact ctgtcgatac cccaccgaga ccccattggg gccaatacgc 1560 ccgcgtttct tccttttccc caccccaccc cccaagttcg ggtgaaggcc cagggctcgc 1620 agccaacgtc ggggcggcag gccctgccat agcagatctg cgcagctggg gctctagggg 1680 gtatccccac gcgccctgta gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag 1740 cgtgaccgct acacttgcca gcgccctagc gcccgctcct ttcgctttct tcccttcctt 1800 tctcgccacg ttcgccggct ttccccgtca agctctaaat cggggcatcc ctttagggtt 1860 ccgatttagt gctttacggc acctcgaccc caaaaaactt gattagggtg atggttcacg 1920 tagtgggcca tcgccctgat agacggtttt tcgccctttg acgttggagt ccacgttctt 1980 taatagtgga ctcttgttcc aaactggaac aacactcaac cctatctcgg tctattcttt 2040 tgatttataa gggattttgg ggatttcggc ctattggtta aaaaatgagc tgatttaaca 2100 aaaatttaac gcgaattaat tctgtggaat gtgtgtcagt tagggtgtgg aaagtcccca 2160 ggctccccag caggcagaag tatgcaaagc atgcatctca attagtcagc aaccaggtgt 2220 ggaaagtccc caggctcccc agcaggcaga agtatgcaaa gcatgcatct caattagtca 2280 gcaaccatag tcccgcccct aactccgccc atcccgcccc taactccgcc cagttccgcc 2340 cattctccgc cccatggctg actaattttt tttatttatg cagaggccga ggccgcctct 2400 gcctctgagc tattccagaa gtagtgagga ggcttttttg gaggcctagg cttttgcaaa 2460 aagctcccgg gagcttgtat atccattttc ggatctgatc aagagacagg atgaggatcg 2520 tttcgcatga ttgaacaaga tggattgcac gcaggttctc cggccgcttg ggtggagagg 2580 ctattcggct atgactgggc acaacagaca atcggctgct ctgatgccgc cgtgttccgg 2640 ctgtcagcgc aggggcgccc ggttcttttt gtcaagaccg acctgtccgg tgccctgaat 2700 gaactgcagg acgaggcagc gcggctatcg tggctggcca cgacgggcgt tccttgcgca 2760 gctgtgctcg acgttgtcac tgaagcggga agggactggc tgctattggg cgaagtgccg 2820 gggcaggatc tcctgtcatc tcaccttgct cctgccgaga aagtatccat catggctgat 2880 gcaatgcggc ggctgcatac gcttgatccg gctacctgcc cattcgacca ccaagcgaaa 2940 catcgcatcg agcgagcacg tactcggatg gaagccggtc ttgtcgatca ggatgatctg 3000 gacgaagagc atcaggggct cgcgccagcc gaactgttcg ccaggctcaa ggcgcgcatg 3060 cccgacggcg aggatctcgt cgtgacccat ggcgatgcct gcttgccgaa tatcatggtg 3120 gaaaatggcc gcttttctgg attcatcgac tgtggccggc tgggtgtggc ggaccgctat 3180 caggacatag cgttggctac ccgtgatatt gctgaagagc ttggcggcga atgggctgac 3240 cgcttcctcg tgctttacgg tatcgccgct cccgattcgc agcgcatcgc cttctatcgc 3300 cttcttgacg agttcttctg agcgggactc tggggttcgc gaaatgaccg accaagcgac 3360 gcccaacctg ccatcacgag atttcgattc caccgccgcc ttctatgaaa ggttgggctt 3420 cggaatcgtt ttccgggacg ccggctggat gatcctccag cgcggggatc tcatgctgga 3480 gttcttcgcc caccccaact tgtttattgc agcttataat ggttacaaat aaagcaatag 3540 catcacaaat ttcacaaata aagcattttt ttcactgcat tctagttgtg gtttgtccaa 3600 actcatcaat gtatcttatc atgtctgtat accgtcgacc tctagctaga gcttggcgta 3660 atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc cacacaacat 3720 acgagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgagct aactcacatt 3780 aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta 3840 atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt ccgcttcctc 3900 gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa 3960 ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa 4020 aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt tccataggct 4080 ccgcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc gaaacccgac 4140 aggactataa agataccagg cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc 4200 gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg tggcgctttc 4260 tcaatgctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca agctgggctg 4320 tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact atcgtcttga 4380 gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta acaggattag 4440 cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta actacggcta 4500 cactagaagg acagtatttg gtatctgcgc tctgctgaag ccagttacct tcggaaaaag 4560 agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt tttttgtttg 4620 caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga tcttttctac 4680 ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc 4740 aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag 4800 tatatatgag taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc 4860 agcgatctgt ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac 4920 gatacgggag ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc 4980 accggctcca gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg 5040 tcctgcaact ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag 5100 tagttcgcca gttaatagtt tgcgcaacgt tgttgccatt gctacaggca tcgtggtgtc 5160 acgctcgtcg tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac 5220 atgatccccc atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag 5280 aagtaagttg gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac 5340 tgtcatgcca tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg 5400 agaatagtgt atgcggcgac cgagttgctc ttgcccggcg tcaatacggg ataataccgc 5460 gccacatagc agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact 5520 ctcaaggatc ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg 5580 atcttcagca tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa 5640 tgccgcaaaa aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt 5700 tcaatattat tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg 5760 tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga 5820 cgtcgacgga tcgggagatc tcccgatccc ctatggtcga ctctcagtac aatctgctct 5880 gatgccgcat agttaagcca gtatctgctc cctgcttgtg tgttggaggt cgctgagtag 5940 tgcgcgagca aaatttaagc tacaacaagg caaggcttga ccgacaattg catgaagaat 6000 ctgcttaggg ttaggcgttt tgcgctgctt cgcgatgtac gggccagata tacgcgttga 6060 cattgattat tgactagtta ttaatagtaa tcaattacgg ggtcattagt tcatagccca 6120 tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg accgcccaac 6180 gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc aatagggact 6240 ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc agtacatcaa 6300 gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg gcccgcctgg 6360 cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat ctacgtatta 6420 gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg tggatagcgg 6480 tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag tttgttttgg 6540 caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt gacgcaaatg 6600 ggcggtaggc gtgtacggtg ggaggtctat ataagcagag ctcgtttagt gaaccgtcag 6660 atcgcctgga gacgccatcc acgctgtttt gacctccata gaagacaccg ggaccgatcc 6720 agcctccgga ctctagagga tcgaaccctt 6750 <210> 38 <211> 9905 <212> DNA <213> Artificial Sequence <220> <223> pcDNA34_syn_S <400> 38 agtacttaat acgactcact ataggctagc gccgccacca tggtgtttgt ttttcttgtt 60 ttattgccac tagtctctag tcagtgtgtt aatcttacaa ccagaactca attaccccct 120 gcatacacta attctttcac acgtggtgtt tattaccctg acaaagtttt cagatcctca 180 gttttacatt caactcagga cttgttctta cctttctttt ccaatgttac ttggttccat 240 gctatacatg tctctgggac caatggtact aagaggtttg ataaccctgt cctaccattt 300 aatgatggtg tttactttgc ttccactgag aagtctaaca taataagagg ctggattttt 360 ggtactactt tagattcgaa aacccagtcc ctacttattg ttaataacgc tactaatgtt 420 gttatcaaag tctgtgaatt tcaattttgt aacgatccat ttttgggtgt ttattaccac 480 aaaaacaaca aaagttggat ggaaagtgag ttcagagttt attctagtgc gaataattgc 540 acttttgaat acgtctctca gccttttctt atggaccttg aaggaaaaca gggtaatttc 600 aaaaatctta gggaatttgt gttcaagaat attgatggtt acttcaagat atactctaag 660 cacacgccta ttaatttagt gcgtgatctc cctcagggtt tttcggcttt agaaccattg 720 gtagatttgc caataggtat taacatcact aggtttcaaa ctttacttgc tttacataga 780 agttatttaa ctcctggtga ttcttcttca ggttggacag ctggtgctgc agcttattat 840 gtgggttatc ttcaacctag gacttttcta ctgaagtaca atgaaaatgg aaccattaca 900 gatgctgtag actgtgcact tgaccctctc tcagaaacaa agtgtacgtt gaaatccttc 960 actgtagaaa aaggaatcta tcaaacttct aactttagag tccaaccaac agaatctatt 1020 gttagatttc ctaacatcac aaacttgtgc ccttttggtg aagtttttaa cgccaccaga 1080 tttgcatctg tttatgcttg gaacaggaag agaatcagca actgtgttgc tgattattct 1140 gtcctgtata attccgcatc attttccact tttaagtgtt atggagtgtc tcctactaaa 1200 ttaaatgatc tctgctttac taatgtctat gcagattcat ttgtaattag aggtgatgaa 1260 gtcagacaaa tcgctccagg gcaaactgga aagattgctg attataacta caaattacca 1320 gatgatttta caggctgcgt tatagcttgg aattctaaca atcttgattc taaggttggt 1380 ggtaattata attacctgta cagattgttt aggaagtcta atctcaaacc ttttgagaga 1440 gatatttcaa ctgaaatcta tcaggccggt agcacacctt gtaatggtgt tgaaggtttt 1500 aattgttact ttcctctgca atcatatggt ttccaaccca ctaatggtgt tggttaccaa 1560 ccatacagag tagtagtact ttcttttgaa cttctacatg caccagcaac tgtttgtgga 1620 cctaaaaagt ctactaattt ggttaagaac aagtgtgtca atttcaactt caatggttta 1680 acaggcacag gtgttcttac tgagtctaac aaaaagtttc tgcctttcca acaatttggc 1740 agagacattg ctgacactac tgatgctgtt cgtgatccac aaacacttga gattcttgac 1800 attacaccat gttcttttgg tggtgtcagt gttataacac caggaacaaa tacttctaac 1860 caggttgctg ttctttatca ggatgttaac tgcacagaag tccctgttgc tattcatgca 1920 gatcaactta ctcctacttg gcgtgtttat tctacaggtt ctaatgtttt tcaaacacgt 1980 gcaggctgtt taataggggc tgaacatgtc aacaactcat atgagtgtga catacccatt 2040 ggtgcaggta tatgcgctag ttatcagact cagactaatt ctcctcggag agcaagaagt 2100 gtagctagtc aatccatcat tgcctacact atgtcacttg gtgcagaaaa ttcagttgct 2160 tactctaata actctattgc catacccaca aattttacta ttagcgttac cacagaaatt 2220 ctaccagtgt ctatgaccaa gacatcagta gattgtacaa tgtacatttg tggtgattca 2280 actgaatgca gcaatctttt gttgcaatat ggcagttttt gtacacaatt aaaccgtgct 2340 ttaactggaa tagctgttga acaagacaaa aacacccaag aagtttttgc acaagtcaaa 2400 caaatttaca agacaccacc aattaaagat tttggcggtt ttaattttag ccagatactg 2460 ccagatccat caaaaccaag caagaggtca tttattgaag atctactgtt caacaaagtg 2520 acacttgcag atgctggctt catcaaacaa tatggtgatt gccttggtga tattgctgct 2580 agagacctca tttgtgcaca aaagtttaac ggccttactg ttttgccacc tttgctcaca 2640 gatgaaatga ttgctcaata cacttctgca ctgttagcag gtacaatcac ttctggttgg 2700 acttttggtg caggtgctgc attacaaata ccatttgcta tgcaaatggc ttataggttt 2760 aatggtattg gagttacaca gaatgttctc tatgagaacc aaaaattgat tgccaaccaa 2820 tttaatagtg ctattggcaa aattcaagac tcactttctt ccacagcaag tgcacttgga 2880 aaacttcaag atgtggtcaa ccaaaatgca caagctttaa acacgcttgt taaacaactt 2940 agctccaatt ttggtgcaat ttcaagtgtt ttaaacgaca tcctttcacg tcttgacaaa 3000 gttgaggctg aagtgcaaat tgataggttg atcacaggca gacttcaaag tttgcagaca 3060 tatgtgactc aacaattaat tagagctgca gaaatcagag cttctgctaa tcttgctgct 3120 actaaaatgt cagagtgtgt acttggacaa tcaaaaagag ttgacttttg cggaaagggc 3180 tatcatctta tgtcatttcc tcagtcagca cctcatggtg tcgtcttttt gcatgtgact 3240 tatgtccctg cacaagaaaa gaacttcaca actgctcctg ccatttgtca tgatggaaaa 3300 gcacactttc ctcgtgaagg tgtctttgtt tcaaatggca cacactggtt tgtaacacaa 3360 aggaattttt atgaaccaca aatcattact acagacaaca catttgtgtc tggtaactgt 3420 gatgttgtaa taggaattgt caacaacaca gtttatgatc ctttgcaacc tgaattagac 3480 tcattcaagg aggagcttga taaatacttc aagaaccata cctcaccaga tgttgattta 3540 ggtgacatct ctggcattaa tgcttcagtt gtaaacattc agaaagaaat cgaccgcctc 3600 aatgaggttg ccaagaattt aaatgaatct ctcatcgatc tccaagaact tggaaagtat 3660 gagcagtata taaaatggcc atggtacatt tggctaggtt ttatagctgg cttgattgcc 3720 atagtaatgg tgacaattat gctttgctgt atgaccagtt gctgtagttg tctcaagggc 3780 tgttgttctt gtggatcctg ctgcaaattt gacgaggacg actctgagcc agtgctcaaa 3840 ggagtcaaat tacattacac ataagcggcc gcttcgagca gacatgataa gataaagggt 3900 tcgatcccta ccggttagta atgagtttga tatctcgaca atcaacctct ggattacaaa 3960 atttgtgaaa gattgactgg tattcttaac tatgttgctc cttttacgct atgtggatac 4020 gctgctttaa tgcctttgta tcatgctatt gcttcccgta tggctttcat tttctcctcc 4080 ttgtataaat cctggttgct gtctctttat gaggagttgt ggcccgttgt caggcaacgt 4140 ggcgtggtgt gcactgtgtt tgctgacgca acccccactg gttggggcat tgccaccacc 4200 tgtcagctcc tttccgggac tttcgctttc cccctcccta ttgccacggc ggaactcatc 4260 gccgcctgcc ttgcccgctg ctggacaggg gctcggctgt tgggcactga caattccgtg 4320 gtgttgtcgg ggaagctgac gtcctttcca tggctgctcg cctgtgttgc cacctggatt 4380 ctgcgcggga cgtccttctg ctacgtccct tcggccctca atccagcgga ccttccttcc 4440 cgcggcctgc tgccggctct gcggcctctt ccgcgtcttc gccttcgccc tcagacgagt 4500 cggatctccc tttgggccgc ctccccgcct ggaaacgggg gaggctaact gaaacacgga 4560 aggagacaat accggaagga acccgcgcta tgacggcaat aaaaagacag aataaaacgc 4620 acgggtgttg ggtcgtttgt tcataaacgc ggggttcggt cccagggctg gcactctgtc 4680 gataccccac cgagacccca ttggggccaa tacgcccgcg tttcttcctt ttccccaccc 4740 caccccccaa gttcgggtga aggcccaggg ctcgcagcca acgtcggggc ggcaggccct 4800 gccatagcag atctgcgcag ctggggctct agggggtatc cccacgcgcc ctgtagcggc 4860 gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc 4920 ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc 4980 cgtcaagctc taaatcgggg catcccttta gggttccgat ttagtgcttt acggcacctc 5040 gaccccaaaa aacttgatta gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg 5100 gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact 5160 ggaacaacac tcaaccctat ctcggtctat tcttttgatt tataagggat tttggggatt 5220 tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttaattctgt 5280 ggaatgtgtg tcagttaggg tgtggaaagt ccccaggctc cccagcaggc agaagtatgc 5340 aaagcatgca tctcaattag tcagcaacca ggtgtggaaa gtccccaggc tccccagcag 5400 gcagaagtat gcaaagcatg catctcaatt agtcagcaac catagtcccg cccctaactc 5460 cgcccatccc gcccctaact ccgcccagtt ccgcccattc tccgccccat ggctgactaa 5520 ttttttttat ttatgcagag gccgaggccg cctctgcctc tgagctattc cagaagtagt 5580 gaggaggctt ttttggaggc ctaggctttt gcaaaaagct cccgggagct tgtatatcca 5640 ttttcggatc tgatcaagag acaggatgag gatcgtttcg catgattgaa caagatggat 5700 tgcacgcagg ttctccggcc gcttgggtgg agaggctatt cggctatgac tgggcacaac 5760 agacaatcgg ctgctctgat gccgccgtgt tccggctgtc agcgcagggg cgcccggttc 5820 tttttgtcaa gaccgacctg tccggtgccc tgaatgaact gcaggacgag gcagcgcggc 5880 tatcgtggct ggccacgacg ggcgttcctt gcgcagctgt gctcgacgtt gtcactgaag 5940 cgggaaggga ctggctgcta ttgggcgaag tgccggggca ggatctcctg tcatctcacc 6000 ttgctcctgc cgagaaagta tccatcatgg ctgatgcaat gcggcggctg catacgcttg 6060 atccggctac ctgcccattc gaccaccaag cgaaacatcg catcgagcga gcacgtactc 6120 ggatggaagc cggtcttgtc gatcaggatg atctggacga agagcatcag gggctcgcgc 6180 cagccgaact gttcgccagg ctcaaggcgc gcatgcccga cggcgaggat ctcgtcgtga 6240 cccatggcga tgcctgcttg ccgaatatca tggtggaaaa tggccgcttt tctggattca 6300 tcgactgtgg ccggctgggt gtggcggacc gctatcagga catagcgttg gctacccgtg 6360 atattgctga agagcttggc ggcgaatggg ctgaccgctt cctcgtgctt tacggtatcg 6420 ccgctcccga ttcgcagcgc atcgccttct atcgccttct tgacgagttc ttctgagcgg 6480 gactctgggg ttcgcgaaat gaccgaccaa gcgacgccca acctgccatc acgagatttc 6540 gattccaccg ccgccttcta tgaaaggttg ggcttcggaa tcgttttccg ggacgccggc 6600 tggatgatcc tccagcgcgg ggatctcatg ctggagttct tcgcccaccc caacttgttt 6660 attgcagctt ataatggtta caaataaagc aatagcatca caaatttcac aaataaagca 6720 tttttttcac tgcattctag ttgtggtttg tccaaactca tcaatgtatc ttatcatgtc 6780 tgtataccgt cgacctctag ctagagcttg gcgtaatcat ggtcatagct gtttcctgtg 6840 tgaaattgtt atccgctcac aattccacac aacatacgag ccggaagcat aaagtgtaaa 6900 gcctggggtg cctaatgagt gagctaactc acattaattg cgttgcgctc actgcccgct 6960 ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg cgcggggaga 7020 ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct gcgctcggtc 7080 gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt atccacagaa 7140 tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc caggaaccgt 7200 aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga gcatcacaaa 7260 aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata ccaggcgttt 7320 ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac cggatacctg 7380 tccgcctttc tcccttcggg aagcgtggcg ctttctcaat gctcacgctg taggtatctc 7440 agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc cgttcagccc 7500 gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag acacgactta 7560 tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt aggcggtgct 7620 acagagttct tgaagtggtg gcctaactac ggctacacta gaaggacagt atttggtatc 7680 tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg atccggcaaa 7740 caaaccaccg ctggtagcgg tggttttttt gtttgcaagc agcagattac gcgcagaaaa 7800 aaaggatctc aagaagatcc tttgatcttt tctacggggt ctgacgctca gtggaacgaa 7860 aactcacgtt aagggatttt ggtcatgaga ttatcaaaaa ggatcttcac ctagatcctt 7920 ttaaattaaa aatgaagttt taaatcaatc taaagtatat atgagtaaac ttggtctgac 7980 agttaccaat gcttaatcag tgaggcacct atctcagcga tctgtctatt tcgttcatcc 8040 atagttgcct gactccccgt cgtgtagata actacgatac gggagggctt accatctggc 8100 cccagtgctg caatgatacc gcgagaccca cgctcaccgg ctccagattt atcagcaata 8160 aaccagccag ccggaagggc cgagcgcaga agtggtcctg caactttatc cgcctccatc 8220 cagtctatta attgttgccg ggaagctaga gtaagtagtt cgccagttaa tagtttgcgc 8280 aacgttgttg ccattgctac aggcatcgtg gtgtcacgct cgtcgtttgg tatggcttca 8340 ttcagctccg gttcccaacg atcaaggcga gttacatgat cccccatgtt gtgcaaaaaa 8400 gcggttagct ccttcggtcc tccgatcgtt gtcagaagta agttggccgc agtgttatca 8460 ctcatggtta tggcagcact gcataattct cttactgtca tgccatccgt aagatgcttt 8520 tctgtgactg gtgagtactc aaccaagtca ttctgagaat agtgtatgcg gcgaccgagt 8580 tgctcttgcc cggcgtcaat acgggataat accgcgccac atagcagaac tttaaaagtg 8640 ctcatcattg gaaaacgttc ttcggggcga aaactctcaa ggatcttacc gctgttgaga 8700 tccagttcga tgtaacccac tcgtgcaccc aactgatctt cagcatcttt tactttcacc 8760 agcgtttctg ggtgagcaaa aacaggaagg caaaatgccg caaaaaaggg aataagggcg 8820 acacggaaat gttgaatact catactcttc ctttttcaat attattgaag catttatcag 8880 ggttattgtc tcatgagcgg atacatattt gaatgtattt agaaaaataa acaaataggg 8940 gttccgcgca catttccccg aaaagtgcca cctgacgtcg acggatcggg agatctcccg 9000 atcccctatg gtcgactctc agtacaatct gctctgatgc cgcatagtta agccagtatc 9060 tgctccctgc ttgtgtgttg gaggtcgctg agtagtgcgc gagcaaaatt taagctacaa 9120 caaggcaagg cttgaccgac aattgcatga agaatctgct tagggttagg cgttttgcgc 9180 tgcttcgcga tgtacgggcc agatatacgc gttgacattg attattgact agttattaat 9240 agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc gttacataac 9300 ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa 9360 tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt 9420 atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc 9480 ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat 9540 gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc atggtgatgc 9600 ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc 9660 tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa 9720 aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg 9780 tctatataag cagagctcgt ttagtgaacc gtcagatcgc ctggagacgc catccacgct 9840 gttttgacct ccatagaaga caccgggacc gatccagcct ccggactcta gaggatcgaa 9900 ccctt 9905 <210> 39 <211> 40556 <212> DNA <213> Artificial Sequence <220> <223> pMR10Y_COVAX191_delN <400> 39 atgaatcgga cgtttgaccg gaaggcatac aggcaagaac tgatcgacgc ggggttttcc 60 gccgaggatg ccgaaaccat cgcaagccgc accgtcatgc gtgcgccccg cgaaaccttc 120 cagtccgtcg gctcgatggt ccagcaagct acggccaaga tcgagcgcga cagcgtgcaa 180 ctggctcccc ctgccctgcc cgcgccatcg gccgccgtgg agcgttcgcg tcgtctcgaa 240 caggaggcgg caggtttggc gaagtcgatg accatcgaca cgcgaggaac tatgacgacc 300 aagaagcgaa aaaccgccgg cgaggacctg gcaaaacagg tcagcgaggc caagcaggcc 360 gcgttgctga aacacacgaa gcagcagatc aaggaaatgc agctttcctt gttcgatatt 420 gcgccgtggc cggacacgat gcgagcgatg ccaaacgaca cggcccgctc tgccctgttc 480 accacgcgca acaagaaaat cccgcgcgag gcgctgcaaa acaaggtcat tttccacgtc 540 aacaaggacg tgaagatcac ctacaccggc gtcgagctgc gggccgacga tgacgaactg 600 gtgtggcagc aggtgttgga gtacgcgaag cgcaccccta tcggcgagcc gatcaccttc 660 acgttctacg agctttgcca ggacctgggc tggtcgatca atggccggta ttacacgaag 720 gccgaggaat gcctgtcgcg cctacaggcg acggcgatgg gcttcacgtc cgaccgcgtt 780 gggcacctgg aatcggtgtc gctgctgcac cgcttccgcg tcctggaccg tggcaagaaa 840 acgtcccgtt gccaggtcct gatcgacgag gaaatcgtcg tgctgtttgc tggcgaccac 900 tacacgaaat tcatatggga gaagtaccgc aagctgtcgc cgacggcccg acggatgttc 960 gactatttca gctcgcaccg ggagccgtac ccgctcaagc tggaaacctt ccgcctcatg 1020 tgcggatcgg attccacccg cgtgaagaag tggcgcgagc aggtcggcga agcctgcgaa 1080 gagttgcgag gcagcggcct ggtggaacac gcctgggtca atgatgacct ggtgcattgc 1140 aaacgctagg gccttgtggg gtcagttccg gctgggggtt cagcagccac tcgatcgagg 1200 tcccaatacg caaaccgcct ctccccgcgc gttggccgat tcattaatgc agctggcacg 1260 acaggtttcc cgactggaaa gcgggcagtg agcgcaacgc aattaatgtg agttagctca 1320 ctcattaggc accccaggct ttacacttta tgcttccggc tcgtatgttg tgtggaattg 1380 tgagcggata acaatttcac acaggaaaca gctatgacca tgattacgcc aagcttccat 1440 gggatatcga gatctcctgc agagctctag agtcgagact agtctcgacg ggcccggtac 1500 cccctcgagg gggccgcact taagttacgc gtggatcgtg gagctttcgg gttttaacta 1560 taacggtcct aaggtagcga actcgggtct tgccttaatc ccaacaaccg gattatctac 1620 acggatttca atagctgata tagcgaatca ccgagattaa ttaataatac gactcactat 1680 agtataagag tgattggcgt ccgtacgtac cctctcaact ctaaaactct tgtagtttaa 1740 atctaatcta aactttataa acggcacttc ctgcgtgtcc atgcccgcgg gcctggtctt 1800 gtcatagtgc tgacatttgt agttccttga ctttcgttct ctgccagtga cgtgtccatt 1860 cggcgccagc agcccaccca taggttgcat aatggcaaag atgggcaaat acggcctggg 1920 cttcaaatgg gccccagaat ttccatggat gcttccgaac gcatcggaga agttgggtaa 1980 ccctgagagg tcagaggagg atgggttttg cccctctgct gcgcaagaac cgaaagttaa 2040 aggaaaaact ttggttaatc acgtgagggt gaattgtagc cggcttccag ctttggaatg 2100 ctgtgttcag tctgccataa tccgtgatat ttttgtagat gaggatcccc agaaggtgga 2160 ggcctcaact atgatggcat tgcagttcgg tagtgccgtc ttggttaagc catccaagcg 2220 cttgtctatt caggcatgga ctaatttggg tgtgcttccc aaaacagctg ccatggggtt 2280 gttcaagcgc gtctgcctgt gtaacaccag ggagtgctct tgtgacgccc acgtggcctt 2340 tcaccttttt acggtccaac ccgatggtgt atgcctgggt aatggccgtt ttataggctg 2400 gttcgttcca gtcacagcca taccggagta tgcgaagcag tggttgcaac cctggtccat 2460 ccttcttcgt aagggtggta acaaagggtc tgtgacatcc ggccacttcc gccgcgctgt 2520 taccatgcct gtgtatgact ttaatgtaga ggatgcttgt gaggaggttc atcttaaccc 2580 gaagggtaag tactcctgca aggcgtatgc cctgctgaag ggctatcgcg gtgttaagcc 2640 catcctgttt gtggaccagt atggttgcga ctatactgga tgtctcgcca agggtcttga 2700 ggactatggc gatctcacct tgagtgagat gaaggagttg ttccctgtgt ggcgtgactc 2760 cttggatagt gaagtccttg tggcttggca cgttgatcga gatcctcggg ctgctatgcg 2820 tctgcagact cttgctactg tacgttgcat tgattatgtg ggccaaccga ccgaggatgt 2880 ggtggatgga gatgtggtag tgcgtgagcc tgctcatctt ctcgcagcca atgccattgt 2940 taaaagactc ccccgtttgg tggagactat gctgtatacg gattcgtccg ttacagaatt 3000 ctgttataaa accaagctgt gtgaatgcgg ttttatcacg cagtttggct atgtggattg 3060 ttgtggtgac acctgtgatt ttcgtgggtg ggttgccggc aatatgatgg atggctttcc 3120 atgtccaggg tgtaccaaaa attatatgcc ctgggaattg gaggcccagt catcaggtgt 3180 tataccagaa ggaggtgttc tattcactca gagcactgat acagtgaatc gtgagtcctt 3240 taagctctac ggtcatgctg ttgtgccttt tggttctgct gtgtattgga gcccttgccc 3300 aggtatgtgg cttccagtaa tttggtcgtc ggttaagtca tactctggtt tgacttatac 3360 aggagtagtt ggttgtaagg caattgttca agagacagac gctatatgtc gttctctgta 3420 tatggattat gtccagcaca agtgtggcaa tctcgagcag agagctatcc ttggattgga 3480 cgatgtctat catagacagt tgcttgtgaa taggggtgac tatagtctcc tccttgagaa 3540 tgtggatttg tttgttaagc ggcgcgctga atttgcttgc aaattcgcca cctgtggaga 3600 tggtcttgta cccctcctac tagatggttt agtgccccgc agttattatt tgattaagag 3660 tggtcaagct ttcacctcta tgatggttaa ttttagccat gaggtgactg acatgtgtat 3720 ggacatggct ttattgttca tgcatgatgt taaagtggcc actaagtatg ttaagaaggt 3780 tactggcaaa ctggccgtgc gctttaaagc gttgggtgta gccgttgtca gaaaaattac 3840 tgaatggttt gatttagccg tggacattgc tgctagtgcc gctggatggc tttgctacca 3900 gctggtaaat ggcttatttg cagtggccaa tggtgttata acctttgtac aggaggtgcc 3960 tgagcttgtc aagaattttg ttgacaagtt caaggcattt ttcaaggttt tgatcgactc 4020 tatgtcggtt tctatcttgt ctggacttac tgttgtcaag actgcctcaa atagggtgtg 4080 tcttgctggc agtaaggttt atgaagttgt gcagaaatct ttgtctgcat atgttatgcc 4140 tgtgggttgc agcgaagcca cttgtttggt gggtgagatt gaacctgcag tttttgaaga 4200 tgatgttgtt gatgtggtta aagccccatt aacatatcaa ggctgttgta agccacccac 4260 ttctttcgag aagatttgta ttgtggataa attgtatatg gccaagtgtg gtgatcaatt 4320 ttaccctgtg gttgttgata acgacactgt tggcgtgtta gatcagtgct ggaggtttcc 4380 ctgtgcgggc aagaaagtcg agtttaacga caagcccaaa gtcaggaaga taccctccac 4440 ccgtaagatt aagatcacct tcgcactgga tgcgaccttt gatagtgttc tttcgaaggc 4500 gtgttcagag tttgaagttg ataaagatgt tacattggat gagctgcttg atgttgtgct 4560 tgacgcagtt gagagtacgc tcagcccttg taaggagcat gatgtgatag gcacaaaagt 4620 ttgtgcttta cttgataggt tggcaggaga ttatgtctat ctttttgatg agggaggcga 4680 tgaagtgatc gccccgagga tgtattgttc cttttctgct cctgatgacg aggactgcgt 4740 tgcagcggat gttgtagatg cagatgaaaa ccaagatgat gatgccgagg actcagcagt 4800 ccttgtcgct gatacccaag aagaggacgg cgttgccaag gggcaggttg aggcggattc 4860 ggaaatttgc gttgcgcata ctggtagtca agaagaattg gctgagcctg atgctgtcgg 4920 atctcaaact cccatcgcct ctgctgagga aaccgaagtc ggagaggcaa gcgacaggga 4980 agggattgct gaggcgaagg caactgtgtg tgctgatgct gtagatgcct gccccgatca 5040 agtggaggca tttgaaattg aaaaggtcga ggactctatc ttggatgagc ttcaaactga 5100 acttaatgcg ccagcggaca agacctatga ggatgtcttg gcattcgatg ccgtatgctc 5160 agaggcgttg tctgcattct atgctgtgcc gagtgatgag acgcacttta aagtgtgtgg 5220 attctattcg cctgctatag agcgcactaa ttgttggctg cgttctactt tgatagtaat 5280 gcagagtcta cctttggaat ttaaagactt ggagatgcaa aagctctggt tgtcttacaa 5340 ggccggctat gaccaatgct ttgtggacaa actagttaag agcgtgccca agtctattat 5400 ccttccacaa ggtggttatg tggcagattt tgcctatttc tttctaagcc agtgtagctt 5460 taaagcttat gctaactggc gttgtttaga gtgtgacatg gagttaaagc ttcaaggctt 5520 ggacgccatg tttttctatg gggacgttgt gtctcatatg tgcaagtgtg gtaatagcat 5580 gaccttgttg tctgcagata taccctacac tttgcatttt ggagtgcgag atgataagtt 5640 ttgcgctttt tacacgccaa gaaaggtctt tagggctgct tgtgcggtag atgttaatga 5700 ttgtcactct atggctgtag tagagggcaa gcaaattgat ggtaaagtgg ttaccaaatt 5760 tattggtgac aaatttgatt ttatggtggg ttacgggatg acatttagta tgtctccttt 5820 tgaactcgcc cagttatatg gttcatgtat aacaccaaat gtttgttttg ttaaaggaga 5880 tgttataaag gttgttcgct tagttaatgc tgaagtcatt gttaaccctg ctaatgggcg 5940 tatggctcat ggtgccggcg tcgccggcgc catagctgaa aaggcgggca gtgcttttat 6000 taaagaaacc tccgatatgg tgaaggctca gggcgtttgc caggttggtg aatgctatga 6060 atctgccggt ggtaagttat gtaaaaaggt gcttaacatt gtagggccag atgcgcgagg 6120 gcatggcaag caatgctatt cacttttaga gcgtgcttat cagcatatta ataagtgtga 6180 caatgttgtc actactttaa tttcggctgg tatatttagt gtgcctactg atgtctccct 6240 aacttactta cttggtgtag tgacaaagaa tgtcattctt gtcagtaaca accaggatga 6300 ttttgatgtg atagagaagt gtcaggtgac ctccgttgct ggtaccaaag cgctatcact 6360 tcaattggcc aaaaatttgt gccgtgatgt aaagtttgtg acgaatgcat gtagttcgct 6420 ttttagtgaa tcttgctttg tctcaagcta tgatgtgttg caggaagttg aagcgctgcg 6480 acatgatata caattggatg atgatgctcg tgtctttgtg caggctaata tggactgtct 6540 gcccacagac tggcgtctcg ttaacaaatt tgatagtgtt gatggtgtta gaaccattaa 6600 gtattttgaa tgcccgggcg ggatttttgt atccagccag ggcaaaaagt ttggttatgt 6660 tcagaatggt tcatttaagg aggcgagtgt tagccaaata agggctttac tcgctaataa 6720 ggttgatgtc ttgtgtactg ttgatggtgt taacttccgc tcctgctgcg tagcagaggg 6780 tgaagttttt ggcaagacat taggttcagt cttttgtgat ggcataaatg tcaccaaagt 6840 taggtgtagt gccatttaca agggtaaggt tttctttcag tacagtgatt tgtccgaggc 6900 agatcttgtg gctgttaaag atgcctttgg ttttgatgaa ccacaactgc tgaagtacta 6960 cactatgctt ggcatgtgta agtggccagt agttgtttgt ggcaattatt ttgctttcaa 7020 gcagtcaaat aataattgct acatcaacgt ggcatgttta atgctgcaac acttgagttt 7080 aaagtttcct aagtggcaat ggcaagaggc ttggaacgag ttccgctctg gtaaaccact 7140 aaggtttgtg tccttggtat tagcaaaggg cagctttaaa tttaatgaac cttctgattc 7200 tatcgatttt atgcgtgtgg tgctacgtga agcagatttg agtggtgcca cgtgcaattt 7260 ggaatttgtt tgtaaatgtg gtgtgaagca agagcagcgc aaaggtgttg acgctgttat 7320 gcattttggt acgttggata aaggtgatct tgtcaggggt tataatatcg catgtacgtg 7380 cggtagtaaa cttgtgcatt gcacccaatt taacgtacca tttttaattt gctccaacac 7440 accagagggt aggaaactgc ccgacgatgt tgttgcagct aatattttta ctggtggtag 7500 tgtgggccat tacacgcatg tgaaatgtaa acccaagtac cagctttatg atgcttgtaa 7560 tgttaataag gtttcggagg ctaagggtaa ttttaccgat tgcctctacc ttaaaaattt 7620 aaagcaaacc ttctcgtctg tgctgacgac tttttattta gatgacgtaa agtgtgtgga 7680 gtataagcca gatttatcgc agtattactg tgagtctggt aaatattata caaaacccat 7740 tattaaggcc caatttagaa catttgagaa ggttgatggt gtctatacca actttaaatt 7800 ggtgggacat agtattgctg aaaaactcaa tgctaagctg ggatttgatt gtaattctcc 7860 ctttgtggag tataaaatta cagagtggcc aacagctact ggagatgtgg tgttggctag 7920 tgatgatttg tatgtaagtc ggtacttaag cgggtgcatt acttttggta aaccggttgt 7980 ctggcttggc catgaggaag catcgctgaa atctctcaca tattttaata gacctagtgt 8040 cgtttgtgaa aataaattta acgtgttgcc cgttgatgtc agtgaaccca cggacaaggg 8100 gcctgtgcct gctgcagtcc ttgttaccgg cgtccctgga gctgatgcgt cagctggtgc 8160 cggtattgcc aaggagcaaa aagcctgtgc ttctgctagt gtggaggatc aggttgttac 8220 ggaggttcgt caagagccat ctgtttcagc tgctgatgtc aaagaggtta aattgaatgg 8280 tgttaaaaag cctgttaagg tggaaggtag tgtggttgtt aatgatccca ctagcgaaac 8340 caaagttgtt aaaagtttgt ctattgttga tgtctatgat atgttcctga cagggtgtaa 8400 gtatgtggtt tggactgcta atgagttgtc tcgactagta aattcaccga ctgttaggga 8460 gtatgtgaag tggggtatgg gaaagattgt aacacccgct aagttgttgt tgttaagaga 8520 tgagaagcaa gagttcgtag cgccaaaagt agtcaaggcg aaagctattg cctgctattg 8580 tgctgtgaag tggtttctcc tctattgttt tagttggata aagtttaata ctgacaataa 8640 ggttatatac accacagaag tagcttcaaa gcttactttc aagttgtgct gtttggcctt 8700 taagaatgcc ttacagacgt ttaattggag cgttgtgtct aggggctttt tcctagttgc 8760 aacggtcttt ttactctggt ttaacttttt gtatgctaat gttattttga gtgacttcta 8820 tttgcctaat attgggcctc tccctacgtt tgtgggacag atagttgcgt ggtttaagac 8880 tacatttggt gtgtcaacca tctgtgattt ctaccaggtg acggatttgg gctatagaag 8940 ttcgttttgt aatggaagta tggtatgtga actatgcttc tcaggttttg atatgctgga 9000 caactatgat gctataaatg ttgttcaaca cgttgtagat aggcgtttgt cctttgacta 9060 tattagccta tttaaactgg tagttgagct tgtaatcggc tactctcttt atactgtgtg 9120 cttctaccca ctgtttgtcc ttattggaat gcagttattg accacatggt tgcctgaatt 9180 ctttatgctg gagactatgc attggagtgc tcgtttgttt gtgtttgttg ccaatatgct 9240 tccagctttt acgttactgc gattttacat cgtggtgaca gctatgtata aggtctattg 9300 tctttgtaga catgttatgt atggatgtag taagcctggt tgcttgtttt gttataagag 9360 aaaccgtagt gtccgtgtta agtgtagcac cgttgttggt ggttcactac gctattacga 9420 tgtaatggct aacggcggca caggtttctg tacaaagcac cagtggaact gtcttaattg 9480 caattcctgg aaaccaggca atacattcat aactcatgaa gcagcggcgg acctctctaa 9540 ggagttgaaa cgccctgtga atccaacaga ttctgcttat tactcggtca cagaggttaa 9600 gcaggttggt tgttccatgc gtttgttcta cgagagagat ggacagcgtg tttatgatga 9660 tgttaatgct agtttgtttg tggacatgaa tggtctgctg cattctaaag ttaaaggtgt 9720 gcctgaaacg catgttgtgg ttgttgagaa tgaagctgat aaagctggtt ttctcggcgc 9780 cgcagtgttt tatgcacaat cgctctacag acctatgttg atggtggaaa agaaattaat 9840 aactaccgcc aacactggtt tgtctgttag tcgaactatg tttgaccttt atgtagattc 9900 attgctgaac gtcctcgacg tggatcgcaa gagtctaaca agttttgtaa atgctgcgca 9960 caactctcta aaggagggtg ttcagcttga acaagttatg gataccttta ttggctgtgc 10020 ccgacgtaag tgtgctatag attctgatgt tgaaaccaag tctattacca agtccgtcat 10080 gtcggcagta aatgctggcg ttgattttac ggatgagagt tgtaataact tggtgcctac 10140 ctatgttaaa agtgacacta tcgttgcagc cgatttgggt gttcttattc agaataatgc 10200 taagcatgta caggctaatg ttgctaaagc cgctaatgtg gcttgcattt ggtctgtgga 10260 tgcttttaac cagctatctg ctgacttaca gcataggctg cgaaaagcat gttcaaaaac 10320 tggcttgaag attaagctta cttataataa gcaggaggca aatgttccta ttttaactac 10380 accgttctct cttaaagggg gcgctgtttt tagtagaatg ttacaatggt tgtttgttgc 10440 taatttgatt tgtttcattg tgttgtgggc ccttatgcca acatatgcag tgcacaaatc 10500 ggatatgcag ttgcctttat atgccagttt taaagttata gataacggtg tgctaaggga 10560 tgtgtctgtt actgacgcat gcttcgcaaa caaatttaat caattcgacc aatggtatga 10620 gtctactttt ggtcttgctt attaccgcaa ctctaaggct tgtcctgttg tggttgctgt 10680 aatagatcaa gacattggcc ataccttatt taatgttcct accacagttt taagatatgg 10740 atttcatgtg ttgcatttta taacccatgc atttgctact gatagcgtgc agtgttacac 10800 gccacatatg caaatcccct atgataattt ctatgctagt ggttgcgtgt tgtcatccct 10860 ctgtactatg cttgcgcatg cagatggaac cccgcatcct tattgttata cagggggtgt 10920 tatgcataat gcctctctgt atagttcttt ggctcctcat gtccgttata acctggctag 10980 ttcaaatggt tatatacgtt ttcccgaagt ggttagtgaa ggcattgtgc gtgttgtgcg 11040 cactcgctct atgacctact gcagggttgg tttatgtgag gaggccgagg agggtatctg 11100 ctttaatttt aatcgttcat gggtattgaa caacccgtat tatagggcca tgcctggaac 11160 tttttgtggt aggaatgctt ttgatttaat acatcaagtt ttaggaggat tagtgcggcc 11220 tattgatttc tttgccttaa cggcgagttc agtggctggt gctatccttg caattattgt 11280 cgttttggct ttctattatt taatcaagct taagcgtgcc tttggtgact acactagtgt 11340 tgtggttatc aatgtaattg tgtggtgtat aaattttctg atgctttttg tgtttcaggt 11400 ttatcccaca ttgtcttgtt tatatgcttg tttctacttc tacaccacgc tttatttccc 11460 ttcggagata agtgttgtta tgcatttgca atggcttgtc atgtatggtg ctattatgcc 11520 cttgtggttt tgcattattt acgtggcagt cgttgtttca aaccatgcat tgtggttgtt 11580 ctcttactgc cgcaaaattg gtaccgaggt tcgtagtgac ggcacatttg aggaaatggc 11640 ccttactacc tttatgatta ctaaagaatc ttattgtaag ttgaaaaact ctgtttctga 11700 tgttgctttt aacaggtact tgagtcttta caacaagtac cgttacttca gtggcaaaat 11760 ggatactgcc gcttatagag aggctgcctg ttcacaactg gcaaaggcaa tggaaacatt 11820 taaccataat aatggtaatg atgttctcta tcagcctcca accgcctctg ttactacatc 11880 atttttacag tctggtatag tgaagatggt gtcgcccacc tctaaagtgg agccttgtat 11940 tgttagtgtt acttatggta acatgacact taatgggttg tggttggatg ataaagttta 12000 ttgcccaaga catgttatct gttcttcagc tgacatgaca gaccctgatt atcctaattt 12060 gctttgtaga gtgacatcaa gtgatttttg tgttatgtct ggtcgtatga gccttactgt 12120 aatgtcttat caaatgcagg gctgccaact tgttttgact gttacactgc aaaatcctaa 12180 cacgcctaag tattccttcg gtgttgttaa gcctggtgag acatttactg tactggctgc 12240 atacaatggc agacctcaag gagccttcca tgttacgctt cgtagtagcc ataccataaa 12300 gggctccttt ctatgtggat cctgcggttc tgtaggatat gttttaactg gcgatagtgt 12360 acgatttgtt tatatgcatc agctagagtt gagtactggt tgtcataccg gtactgactt 12420 tagtgggaac ttttatggtc cctatagaga tgcgcaagtt gtacaattgc ctgttcagga 12480 ttatacgcag actgttaatg ttgtagcttg gctttatgct gctattttta acagatgcaa 12540 ctggtttgtg caaagtgata gttgttccct ggaggagttt aatgtttggg ctatgaccaa 12600 tggttttagc tcaatcaaag ccgatcttgt cttggatgcg cttgcttcta tgacaggcgt 12660 tacagttgaa caggtgttgg ccgctattaa gaggctgcat tctggattcc agggcaaaca 12720 aattttaggt agttgtgtgc ttgaagatga gctgacacca agtgatgttt atcaacaact 12780 agctggtgtc aagctacagt caaagcgcac aagagttata aaaggtacat gttgctggat 12840 attggcttca acgtttttgt tctgtagcat tatctcagca tttgtaaaat ggactatgtt 12900 tatgtatgtt actacccata tgttgggagt gacattgtgt gcactttgtt ttgtaagctt 12960 tgctatgttg ttgatcaagc ataagcattt gtatttaact atgtacatca tgcctgtgtt 13020 atgcacactg ttttacacca actatttggt tgtgtacaaa cagagtttta gaggtctagc 13080 ttatgcttgg ctttcacact ttgtccctgc tgtagattat acatatatgg atgaagtttt 13140 atatggtgtt gtgttgctag tagctatggt gtttgttacc atgcgtagca taaaccacga 13200 cgtcttttct attatgttct tggttggtag acttgtcagc ctggtatcca tgtggtattt 13260 tggagccaat ttagaggaag aggtactatt gttcctcaca tccctatttg gcacgtacac 13320 atggactact atgttgtcat tggctaccgc taaggttatt gctaaatggt tggctgtgaa 13380 tgtcttgtac ttcacagacg taccgcaaat taaattagtt ctgttgagct acttgtgtat 13440 tggttatgtg tgttgttgtt attggggaat cttgtcactc cttaatagca tttttaggat 13500 gccattgggc gtctacaatt ataaaatctc cgttcaggag ttacgttata tgaatgctaa 13560 tggcttgcgc ccacctagaa atagttttga ggccctgatg cttaatttta agctgttggg 13620 aattggtggt gtgccagtca ttgaagtatc tcaaattcaa tcaagattga cggatgttaa 13680 atgtgctaat gttgtgttgc ttaattgcct ccagcacttg catattgcat ctaattctaa 13740 gttgtggcag tattgtagta ctttgcacaa tgaaatactg gctacatctg atttgagcgt 13800 ggccttcgat aagttggctc aactcttagt tgttttattt gctaatccag cagcagtgga 13860 tagcaagtgc cttgcaagta ttgaagaagt gagcgatgat tacgttcgcg acaatactgt 13920 cttgcaagcc ttacagagtg aatttgttaa tatggctagc ttcgttgagt atgaacttgc 13980 taagaagaat ctagatgagg ctaaggctag cggctctgcc aatcaacagc agattaagca 14040 gctagagaag gcgtgtaata ttgctaagtc agcatatgag cgcgacagag ctgttgctcg 14100 taagctggaa cgtatggctg atttagctct tacaaacatg tataaagaag ctagaattaa 14160 tgataagaag agtaaggtag tgtctgcatt gcaaaccatg ctctttagta tggtgcgtaa 14220 gctagataac caagctctta attctatttt agacaacgca gttaagggtt gtgtaccttt 14280 gaatgcaata ccatcattga cttcgaacac tctgactata atagtgccag ataagcaggt 14340 ttttgatcag gttgtggata atgtgtatgt cacctatgct gggaatgtat ggcatataca 14400 gtttattcaa gatgctgatg gtgctgttaa acaattgaat gagatagatg ttaattcaac 14460 ctggcctcta gtcattgctg caaataggca taatgaagtg tctactgttg ttttgcagaa 14520 caatgagttg atgcctcaga agttgagaac tcaggttgtc aatagtggct cagatatgaa 14580 ttgtaatact cctacccagt gttactataa tactactggc acgggtaaga ttgtgtatgc 14640 tatacttagt gactgtgacg gcctgaagta cactaagata gtaaaagaag atggaaattg 14700 tgttgttttg gaattggatc ctccctgtaa gttttctgtt caggatgtga agggccttaa 14760 aattaagtac ctttactttg tgaaggggtg taatacactg gctagaggct gggttgtagg 14820 caccttatcc tcgacagtga gattgcaggc gggtacggca actgagtatg cctccaactc 14880 tgcaatactg tcgctgtgtg cgttttctgt agatcctaag aaaacgtact tggattatat 14940 aaaacagggt ggagttcccg ttactaattg tgttaagatg ttatgtgacc atgctggcac 15000 tggtatggcc attactatta agccggaggc aaccactaat caggattctt atggtggtgc 15060 ttccgtttgt atatattgcc gctcgcgtgt tgaacatcca gatgttgatg gattgtgcaa 15120 attacgcggc aagtttgtcc aagtgccctt aggcataaaa gatcctgtgt catatgtgtt 15180 gacgcatgat gtttgtcagg tttgtggctt ttggcgagat ggtagctgtt cctgtgtagg 15240 cacaggctcc cagtttcagt caaaagacac gaacttttta aacggattcg gggtacaagt 15300 gtaaatgccc gtcttgtacc ctgtgccagt ggcttggaca ctgatgttca attaagggca 15360 tttgacattt gtaatgctaa tcgagctggc attggtttgt attataaagt gaattgctgc 15420 cgcttccagc gtgtagatga ggacggcaac aagttggata agttctttgt tgttaaaaga 15480 actaatttag aagtgtataa caaggagaaa gaatgctatg agttgacaaa agaatgcggt 15540 gttgtggctg aacacgagtt cttcacattt gatgtggagg gaagtcgggt accacacata 15600 gtccgtaaag atctttcaaa gtttactatg ttagatcttt gctatgcatt gcgtcatttt 15660 gaccgcaatg attgttcaac tcttaaggaa attctcctta catatgctga gtgtgaagag 15720 tcctacttcc aaaagaagga ctggtatgat tttgttgaga atcctgatat aattaatgtg 15780 tacaagaagc ttggtcctat atttaataga gccctgctta acactgccaa gtttgcagac 15840 gcattagtgg aggcaggctt agtaggtgtt ttaacacttg ataatcaaga tttatatggt 15900 caatggtatg actttggaga ttttgtcaag acagtacctg gttgtggtgt tgccgtggca 15960 gactcttatt attcatatat gatgccaatg ctgactatgt gtcatgcgtt ggatagtgag 16020 ttgtttgtta atggtactta tagggagttt gaccttgttc agtatgattt tactgatttc 16080 aagctagagc tgttcactaa gtattttaag cattggagta tgacctacca cccgaacacc 16140 tgtgagtgcg aggatgacag gtgcattatt cattgcgcca attttaatat acttttcagc 16200 atggtcttac ctaagacctg ttttgggcct cttgttaggc agatatttgt ggatggtgtt 16260 cctttcgttg tgtcgatcgg ttaccattat aaagaattag gtgttgttat gaatatggat 16320 gtggatacac atcgttatcg cttgtctctt aaggacttgc ttttgtatgc tgcagaccct 16380 gcccttcatg tggcgtctgc tagtgcactg cttgatttgc gcacatgttg ttttagcgtt 16440 gcagctatta caagtggcgt aaaatttcaa acagttaaac ctggaaattt taatcaggat 16500 ttctacgagt ttattttgag taaaggcctg cttaaagagg ggagctccgt tgatttgaag 16560 cacttcttct ttacgcagga tggtaatgct gctattactg attacaatta ctacaagtat 16620 aatctaccca ccatggtgga tattaagcag ttgttgtttg ttttagaagt tgttaataag 16680 tacttcgaga tctatgaggg tgggtgtata cccgcaacac aggtcattgt taataattat 16740 gacaagagtg ctggctatcc atttaataaa tttggaaagg ccaggctcta ttatgaggca 16800 ttatcatttg aggagcagga tgaaatttat gcgtatacca aacgcaatgt cctgccgacc 16860 ctaactcaaa tgaatcttaa atatgctatt agtgctaaga atagggcccg caccgttgct 16920 ggtgtctcta ttctcagtac tatgactggc agaatgtttc atcaaaagtg tctaaagagt 16980 atagcagcta ctcgcggtgt tcctgtagtt ataggcacca cgaagttcta tggcggttgg 17040 gatgatatgt tacgccgcct tattaaagat gttgatagtc ctgtactcat gggttgggac 17100 tatcctaaat gtgatcgtgc tatgccaaac atactgcgta ttgttagtag tttggtgcta 17160 gcccgtaaac atgattcgtg ctgttcgcat acggatagat tctatcgtct tgcgaacgag 17220 tgcgcccaag ttttgagtga aattgttatg tgtggtggtt gttattatgt taaaccaggt 17280 ggcactagta gtggggatgc aaccactgct tttgctaatt ctgtgtttaa catttgtcaa 17340 gctgtttccg ccaatgtatg ctcgcttatg gcatgcaatg gacacaaaat tgaagatttg 17400 agtatacgcg agttacaaaa gcgcctatac tctaatgtct atcgtgcgga ccatgttgac 17460 cccgcatttg ttagtgagta ttatgagttt ttaaacaagc attttagtat gatgattttg 17520 agtgatgatg gtgttgtgtg ttataattca gagtttgcgt ccaagggtta tattgctaat 17580 ataagtgcct ttcaacaggt attatattat caaaacaacg tgtttatgtc tgaggccaaa 17640 tgttgggtag aaacagacat cgaaaaggga ccgcatgaat tttgttctca acatacaatg 17700 ctagtcaaga tggatggtga tgaagtctac cttccatacc ctgatccttc gagaatctta 17760 ggagcaggct gttttgttga tgatttactc aagactgata gcgttctctt gatagagcgt 17820 ttcgtaagtc ttgcaattga tgcttatcct ttagtatacc atgagaaccc agagtatcaa 17880 aatgtgttcc gggtatattt agaatacatc aagaagctgt acaatgatct cggtaatcag 17940 atcctggaca gctacagtgt tattttaagt acttgtgatg gtcaaaagtt tactgacgag 18000 acgttttaca agaacatgta tttaagaagt gcagtgctgc aaagcgttgg tgcctgcgtt 18060 gtctgtagtt ctcaaacatc attacgttgt ggcagttgca tacgcaagcc tttgctgtgt 18120 tgcaaatgcg cctatgatca tgttatgtcc actgatcata aatatgtcct gagtgtgtca 18180 ccatatgtgt gtaattcacc gggatgtgat gtaaatgatg ttaccaaatt gtatttaggt 18240 ggtatgtcat attattgtga ggaccataaa ccacagtatt cattcaaatt ggtgatgaat 18300 ggtatggttt ttggtttata taagcagtct tgtactggtt cgccctacat agaggatttt 18360 aataaaatcg ctagttgcaa atggacagaa gtcgatgatt atgtgctagc taatgaatgc 18420 accgaacgcc ttaaattgtt tgccgcagaa acgcagaagg ccacagaaga ggcctttaag 18480 caatgttatg cgtcagcaac gatccgtgag atcgtgagcg atcgggagtt aattttatct 18540 tgggaaattg gtaaagtccg cccgccactt aataaaaatt acgtgttcac cggctaccat 18600 tttactaata atggtaagac agttttaggt gagtatgttt ttgataagag tgagttgact 18660 aatggtgtgt attatcgcgc cacaaccact tataagttat ctgtaggtga tgtgttcatt 18720 ttaacatcac acgcagtgtc tagtttaagt gctcctacat tagtaccgca ggagaattat 18780 actagcattc gttttgctag tgtttatagt gtgcctgaga cgtttcagaa taatgtgcct 18840 aattatcagc acattggaat gaagcgctat tgtactgtac agggaccgcc tggtactggt 18900 aagtcccatc tagccattgg gctagctgtt tattattgta cagcgcgcgt ggtgtatacc 18960 gctgctagcc atgctgcagt tgacgcgctg tgtgaaaagg cacataaatt tctcaacatc 19020 aacgactgca cgcgtattgt tcctgcaaag gtgcgtgtag attgttatga taaattcaag 19080 gtcaatgaca ccactcgcaa gtatgtgttt actacaataa atgcattacc tgagttggtg 19140 actgacatta ttgtcgttga tgaagttagt atgcttacca actatgagct gtctgttatt 19200 aacagtcgtg ttagggctaa gcattatgtg tatattggcg acccggcgca gttacctgca 19260 ccacgtgtgc tactgaataa gggaactcta gaacctagat attttaattc cgttaccaag 19320 ctaatgtgtt gtttgggtcc agatattttc ttgggcacct gttatagatg ccctaaggag 19380 attgtggata cggtgtcagc cttggtttat aataataagc tgaaggctaa aaatgataat 19440 agctccatgt gctttaaggt ttattataag ggccagacta cacatgagag ttctagtgct 19500 gttaatatgc agcaaataca tttaatttcc aagtttctga aggcaaaccc cagttggagt 19560 aacgccgtat ttattagtcc ttataactcg cagaactatg ttgctaagag agtcttggga 19620 ttacaaaccc agacagtaga ctcagcgcag ggttctgaat atgattttgt tatctactca 19680 cagactgcgg aaacagcgca ttctgtcaat gtaaatagat tcaatgttgc tattacacgt 19740 gctaagaagg gtattctctg tgtcatgagt agtatgcaat tatttgagtc tcttaatttt 19800 actacactga cgttggataa gattaacaat ccacgattac agtgtactac aaatttgttt 19860 aaggattgta gcaggagcta tgtaggatat cacccagccc atgcaccatc ctttttggca 19920 gttgatgaca aatataaggt aggcggtgat ttagccgttt gccttaatgt tgctgattct 19980 gctgtcactt attcgcggct tatatcactc atgggattca agcttgactt gacccttgat 20040 ggttattgta agctgtttat aactagagat gaagctatca aacgtgttag agcctgggtt 20100 ggcttcgatg cagaaggtgc ccatgcgata cgtgatagca ttgggacaaa tttcccatta 20160 caattaggct tttcgactgg aattgatttt gttgtcgaag ccactggaat gtttgctgag 20220 agagatggtt atgtctttaa aaaggcagcc gcacgagctc ctcctggcga acaatttaaa 20280 caccttatcc cacttatgtc aagagggcag aaatgggatg tggttcgcat tagaatagta 20340 caaatgttgt cagaccacct agtggatttg gcagacagtg ttgtacttgt gacgtgggct 20400 gccagctttg agctcacatg tttgcgatat ttcgctaaag ttggaagaga agttgtgtgt 20460 agtgtctgca ccaagcgtgc gacatgtttt aattctagaa ctggatacta tggatgctgg 20520 cgacatagtt attcctgtga ttacctgtac aacccactaa tagttgacat tcaacagtgg 20580 ggatatacag gatctttaac tagcaatcat gatcctattt gcagcgtgca taagggtgct 20640 catgttgcat catctgatgc tatcatgacc cggtgtctag ctgttcatga ttgcttttgt 20700 aagtctgtta attggaattt agaatacccc attatttcaa atgaggtcag tgttaatacc 20760 tcctgcaggt tattgcagcg cgtaatgttt agggctgcga tgctatgcaa taggtatgat 20820 gtgtgttatg acattggcaa ccctaaaggt cttgcctgtg tcaaaggata tgattttaag 20880 ttctatgacg cctcccctgt tgttaagtct gttaaacagt ttgtttacaa atacgaggca 20940 cataaagatc aatttttaga tggtttgtgt atgttttgga actgcaatgt ggataagtat 21000 ccagcgaatg cagttgtgtg taggtttgac acgcgtgtgt tgaacaaatt aaatctccct 21060 ggctgtaatg gtggcagttt gtatgttaac aaacatgcat tccacaccag tccctttacc 21120 cgggctgcct tcgagaattt gaagcctatg cctttctttt attattcaga tacgccctgt 21180 gtgtatatgg aaggcatgga atctaagcag gtcgattatg tcccattgag aagcgctaca 21240 tgcatcacaa gatgcaattt aggtggcgct gtttgtttaa aacatgctga ggagtatcgt 21300 gagtaccttg agtcttacaa tacggcaacc acagcgggtt ttactttttg ggtctataag 21360 acttttgatt tttacaacct ttggaatact tttactaggc tccaaagttt agaaaatgta 21420 gtgtataacc tggtcaacgc tggacacttt gatggccggg cgggtgaact gccttgtgct 21480 gttataggtg agaaagtcat tgccaagatt caaaatgagg atgtcgtggt ctttaaaaat 21540 aacacgccat tccccactaa tgtggctgtc gaattatttg ctaagcgcag tattcggccc 21600 caccccgagc ttaagctctt tagaaatttg aatattgacg tgtgctggag tcacgtcctt 21660 tgggattatg ctaaggatag tgtgttttgc agttcgacgt ataaggtctg caaatacaca 21720 gatttacagt gcattgaaag cttgaatgta ctttttgatg gtcgtgataa tggtgctctt 21780 gaagctttta agaagtgccg gaatggcgtc tacattaaca cgacaaaaat taaaagtctg 21840 tcgatgatta aaggcccaca acgtgccgat ttgaatggcg tagttgtgga gaaagttgga 21900 gattctgatg tggaattttg gtttgctgtg cgtaaagacg gtgacgatgt tatcttcagc 21960 cgtacaggga gccttgaacc gagccattac cggagcccac aaggtaatcc gggtggtaat 22020 cgcgtgggtg atctcagcgg taatgaagct ctagcgcgtg gcactatctt tactcaaagc 22080 agattattat cttctttcac acctcgatca gagatggaga aagattttat ggatttagat 22140 gatgatgtgt tcattgcaaa atatagttta caggactacg cgtttgaaca cgttgtttat 22200 ggtagtttta accagaagat tattggaggt ttgcatttgc ttattggctt agcccgtagg 22260 cagcaaaaat ccaatctggt aattcaagag ttcgtgacat acgactctag cattcattcg 22320 tactttatca ctgacgagaa cagtggtagt agtaagagtg tgtgcactgt tattgattta 22380 ttgttagatg attttgtgga cattgtaaag tccctgaatc taaagtgtgt gagtaaggtt 22440 gttaatgtta atgtggattt taaggacttc cagtttatgt tgtggtgcaa tgaggagaag 22500 gtcatgactt tctatcctcg tttgcaggct gctgctgact ggaaacctgg ttatgttatg 22560 cctgtcttat ataagtattt ggaatcgcct ctggaaagag taaacctctg gaattatggc 22620 aagccgatta ctttacctac aggatgtatg atgaatgttg ctaagtatac tcaattatgt 22680 caatatttga gcactacaac attagcagtt ccggctaata tgcgtgtctt acaccttggt 22740 gccggttcgg ataagggtgt tgcccctggg tctgcagttc ttaggcagtg gctaccagcg 22800 ggaagtattc ttgtagataa tgatgtgaat ccatttgtga gtgacagtgt cgcctcatat 22860 tatggaaatt gtataacctt accctttgat tgtcagtggg atctgataat ttctgatatg 22920 tacgaccctc ttactaagaa cattggggag tacaacgtga gtaaagatgg attctttact 22980 tacctctgtc atttaattcg tgacaagttg gctctgggtg gcagtgttgc cataaaaata 23040 acagagtttt cttggaacgc tgagttatat agtttaatgg ggaagtttgc gttctggaca 23100 atcttttgca ccaacgtaaa cgcctcttca agtgaaggat ttttgattgg cataaattgg 23160 ttgaataaga cccgtaccga aattgacggt aaaaccatgc atgccaatta tctgttttgg 23220 agaaatagta caatgtggaa tggaggggct tacagtctct ttgacatgag taagttccct 23280 ttgaaagcgg ctggtacggc tgttgttagc cttaaaccag accaaataaa tgacttagtc 23340 ctctccttga ttgagaaggg caagttatta gtgcgtgata cacgcaaaga agtttttgtt 23400 ggcgatagcc tagtaaatgt caaataaatc tatacttgtc gtggctgtga aaatggcctt 23460 tgctgacaag cctaatcatt tcataaactt tcccctggcc caatttagtg gctttatggg 23520 taagtattta aagctacagt ctcaacttgt ggaaatgggt ttagactgta aattacagaa 23580 ggcaccacat gttagtatta ccctgcttga tattaaagca gaccaataca aacaggtgga 23640 atttgcaata caagaaataa tagatgatct ggcggcatat gagggagata ttgtctttga 23700 caaccctcac atgcttggca gatgccttgt tcttgatgtt agaggatttg aagagttgca 23760 tgaagatatt gttgaaattc tccgcagaag gggttgcacg gcagatcaat ccagacactg 23820 gattccgcac tgcactgtgg cccaatttga cgaagaaaga gaaacaaaag gaatgcaatt 23880 ctatcataaa gaacccttct acctcaagca taacaaccta ttaacggatg ctgggcttga 23940 gctcgtgaag ataggttctt ccaaaataga tgggttttat tgtagtgaac tgagtgtttg 24000 gtgtggtgag aggctttgtt ataagcctcc aacacccaaa ttcagtgata tatttggcta 24060 ttgctgcata gataaaatac gtggtgattt agaaataggc gacctgccgc aggatgatga 24120 ggaagcgtgg gccgagctaa gttaccacta tcaaagaaac acctacttct tcagacatgt 24180 gcacgataat agcatctatt ttcgtaccgt gtgtagaatg aagggttgta tgtgttgatt 24240 tgtttttaca ctattagtgt aataagctta ttattttgtt gaaaagggca ggatgtgcat 24300 agctatggct cctcgcacac tgcttttgct gatttgatgt cagctggtgt ttgggttcaa 24360 tgaacctctt aacatcgttt cacatttaaa tgatgactgg tttctatttg gtgacagtcg 24420 gtccgactgt acctatgtag aaaataacgg tcatcctaaa ttagattggc ttgacctcga 24480 cccaaagttg tgtaattcag gaaagatttc cgcaaagagt ggtaactctc tctttaggag 24540 ttttcacttc actgattttt acaattatac gggtgaggga taccaaattg tattttatga 24600 aggagttaat tttagtccca gccatggctt taaatgcctg gctcatggag ataataaaag 24660 atggatgggc aataaagctc gattttatgc ccgagtgtat gagaagatgg cccaatatag 24720 gagcctatcg tttgttaatg tgtcttatgc ctatggaggt aatgcaaagc ccgcctccat 24780 ttgcaaagac aatactttaa cactcaataa ccccaccttc atatcgaagg agtctaatta 24840 tgttgattac tactacgaga gtgaggctaa tttcacacta gaaggttgtg atgaatttat 24900 agtaccgctc tgtggtttta atggccattc caagggctcg tcgtcggatg ctgccaataa 24960 atattatact gactctcaga gttactataa tatggatatt ggtgtcttat atgggttcaa 25020 ttcgaccttg gatgttggca acactgctaa ggatccgggt cttgatctca cttgtaggta 25080 tcttgcattg actcctggta attataaggc tgtgtcctta gaatatttgt taagcttacc 25140 ctcaaaggct atttgcctcc ataagacaaa gcgctttatg cctgtgcagg tagttgactc 25200 aaggtggagt agcatccgcc agtcagacaa tatgaccgct gcagcctgtc agctgccata 25260 ttgtttcttt cgcaacacat ctgcgaatta tagtggtggc acacatgatg cgcaccatgg 25320 tgattttcat ttcaggcagt tattgtctgg tttgttatat aatgtttcct gtattgccca 25380 gcagggtgca tttctttata ataatgtgtc gtcctcttgg ccagcctatg ggtacggtca 25440 ttgtccaacg gcagctaaca ttggttatat ggcacctgtt tgtatctatg accctctccc 25500 ggtcatactg ctaggtgtgt tattgggtat agctgtgttg actattgtgt ttctgatgtt 25560 ttattttatg acggatagcg gtgttagatt gcatgaggca taatctaaac atgtttgttt 25620 ttcttgtttt attgccacta gtctctagtc agtgtgttaa tcttacaacc agaactcaat 25680 taccccctgc atacactaat tctttcacac gtggtgttta ttaccctgac aaagttttca 25740 gatcctcagt tttacattca actcaggact tgttcttacc tttcttttcc aatgttactt 25800 ggttccatgc tatacatgtc tctgggacca atggtactaa gaggtttgat aaccctgtcc 25860 taccatttaa tgatggtgtt tactttgctt ccactgagaa gtctaacata ataagaggct 25920 ggatttttgg tactacttta gattcgaaaa cccagtccct acttattgtt aataacgcta 25980 ctaatgttgt tatcaaagtc tgtgaatttc aattttgtaa cgatccattt ttgggtgttt 26040 attaccacaa aaacaacaaa agttggatgg aaagtgagtt cagagtttat tctagtgcga 26100 ataattgcac ttttgaatac gtctctcagc cttttcttat ggaccttgaa ggaaaacagg 26160 gtaatttcaa aaatcttagg gaatttgtgt tcaagaatat tgatggttac ttcaagatat 26220 actctaagca cacgcctatt aatttagtgc gtgatctccc tcagggtttt tcggctttag 26280 aaccattggt agatttgcca ataggtatta acatcactag gtttcaaact ttacttgctt 26340 tacatagaag ttatttaact cctggtgatt cttcttcagg ttggacagct ggtgctgcag 26400 cttattatgt gggttatctt caacctagga cttttctact gaagtacaat gaaaatggaa 26460 ccattacaga tgctgtagac tgtgcacttg accctctctc agaaacaaag tgtacgttga 26520 aatccttcac tgtagaaaaa ggaatctatc aaacttctaa ctttagagtc caaccaacag 26580 aatctattgt tagatttcct aacatcacaa acttgtgccc ttttggtgaa gtttttaacg 26640 ccaccagatt tgcatctgtt tatgcttgga acaggaagag aatcagcaac tgtgttgctg 26700 attattctgt cctgtataat tccgcatcat tttccacttt taagtgttat ggagtgtctc 26760 ctactaaatt aaatgatctc tgctttacta atgtctatgc agattcattt gtaattagag 26820 gtgatgaagt cagacaaatc gctccagggc aaactggaaa gattgctgat tataactaca 26880 aattaccaga tgattttaca ggctgcgtta tagcttggaa ttctaacaat cttgattcta 26940 aggttggtgg taattataat tacctgtaca gattgtttag gaagtctaat ctcaaacctt 27000 ttgagagaga tatttcaact gaaatctatc aggccggtag cacaccttgt aatggtgttg 27060 aaggttttaa ttgttacttt cctctgcaat catatggttt ccaacccact aatggtgttg 27120 gttaccaacc atacagagta gtagtacttt cttttgaact tctacatgca ccagcaactg 27180 tttgtggacc taaaaagtct actaatttgg ttaagaacaa gtgtgtcaat ttcaacttca 27240 atggtttaac aggcacaggt gttcttactg agtctaacaa aaagtttctg cctttccaac 27300 aatttggcag agacattgct gacactactg atgctgttcg tgatccacaa acacttgaga 27360 ttcttgacat tacaccatgt tcttttggtg gtgtcagtgt tataacacca ggaacaaata 27420 cttctaacca ggttgctgtt ctttatcagg atgttaactg cacagaagtc cctgttgcta 27480 ttcatgcaga tcaacttact cctacttggc gtgtttattc tacaggttct aatgtttttc 27540 aaacacgtgc aggctgttta ataggggctg aacatgtcaa caactcatat gagtgtgaca 27600 tacccattgg tgcaggtata tgcgctagtt atcagactca gactaattct cctcggagag 27660 caagaagtgt agctagtcaa tccatcattg cctacactat gtcacttggt gcagaaaatt 27720 cagttgctta ctctaataac tctattgcca tacccacaaa ttttactatt agcgttacca 27780 cagaaattct accagtgtct atgaccaaga catcagtaga ttgtacaatg tacatttgtg 27840 gtgattcaac tgaatgcagc aatcttttgt tgcaatatgg cagtttttgt acacaattaa 27900 accgtgcttt aactggaata gctgttgaac aagacaaaaa cacccaagaa gtttttgcac 27960 aagtcaaaca aatttacaag acaccaccaa ttaaagattt tggcggtttt aattttagcc 28020 agatactgcc agatccatca aaaccaagca agaggtcatt tattgaagat ctactgttca 28080 acaaagtgac acttgcagat gctggcttca tcaaacaata tggtgattgc cttggtgata 28140 ttgctgctag agacctcatt tgtgcacaaa agtttaacgg ccttactgtt ttgccacctt 28200 tgctcacaga tgaaatgatt gctcaataca cttctgcact gttagcaggt acaatcactt 28260 ctggttggac ttttggtgca ggtgctgcat tacaaatacc atttgctatg caaatggctt 28320 ataggtttaa tggtattgga gttacacaga atgttctcta tgagaaccaa aaattgattg 28380 ccaaccaatt taatagtgct attggcaaaa ttcaagactc actttcttcc acagcaagtg 28440 cacttggaaa acttcaagat gtggtcaacc aaaatgcaca agctttaaac acgcttgtta 28500 aacaacttag ctccaatttt ggtgcaattt caagtgtttt aaacgacatc ctttcacgtc 28560 ttgacaaagt tgaggctgaa gtgcaaattg ataggttgat cacaggcaga cttcaaagtt 28620 tgcagacata tgtgactcaa caattaatta gagctgcaga aatcagagct tctgctaatc 28680 ttgctgctac taaaatgtca gagtgtgtac ttggacaatc aaaaagagtt gacttttgcg 28740 gaaagggcta tcatcttatg tcatttcctc agtcagcacc tcatggtgtc gtctttttgc 28800 atgtgactta tgtccctgca caagaaaaga acttcacaac tgctcctgcc atttgtcatg 28860 atggaaaagc acactttcct cgtgaaggtg tctttgtttc aaatggcaca cactggtttg 28920 taacacaaag gaatttttat gaaccacaaa tcattactac agacaacaca tttgtgtctg 28980 gtaactgtga tgttgtaata ggaattgtca acaacacagt ttatgatcct ttgcaacctg 29040 aattagactc attcaaggag gagcttgata aatacttcaa gaaccatacc tcaccagatg 29100 ttgatttagg tgacatctct ggcattaatg cttcagttgt aaacattcag aaagaaatcg 29160 accgcctcaa tgaggttgcc aagaatttaa atgaatctct catcgatctc caagaacttg 29220 gaaagtatga gcagtatata aaatggccat ggtacatttg gctaggtttt atagctggct 29280 tgattgccat agtaatggtg acaattatgc tttgctgtat gaccagttgc tgtagttgtc 29340 tcaagggctg ttgttcttgt ggatcctgct gcaaatttga cgaggacgac tctgagccag 29400 tgctcaaagg agtcaaatta cattacacat aactatcaca gcctctcctg gaaagacaga 29460 aaatctaaac aatttatagc attctcattg ctacctggcc ccgtaagagg cagtcatagc 29520 tatggccgtg ttggtcctaa ggctacattg gctgctgtct ttattggtcc atttattgta 29580 gcatgtatgc taggcattgg cctagtttat ttattgcaat tgcaagttca aatttttcat 29640 gttaaggata ccatacgtgt gactggcaag ccagccactg tgtcttatac tacaagtaca 29700 ccagtaacac cgagcgcgac gacgctcgat ggtactacgt atactttaat tagacccact 29760 agctcttata caagagttta tcttggtact ccaagaggtt ttgattatag tacatttggg 29820 cctaagaccc tagattatgt tactaatcta aacctcatct taattctggt cgtccatata 29880 cttttaaggc attgtccagg catatgaggc caacagccac atggatttgg catgtgagtg 29940 atgcatggtt acgccgcacg cgggactttg gtgtcattcg cctagaagat ttttgttttc 30000 aatttaatta tagccaaccc cgagttggtt attgtagagt tcctttaaag gcttggtgta 30060 gcaaccaggg taaatttgca gcgcagttta ccctaaaaag ttgcgaaaaa ccaggtcacg 30120 aaaaatttat tactagcttc acggcctacg gcagaactgt ccaacaggcc gttagcaagt 30180 tagtagaaga agctgttgat tttattcttt ttagggccac gcagctcgaa agaaatgttt 30240 aatttattcc ttacagacac agtatggtat gtggggcaga ttatttttat attcgcagtg 30300 tgtttgatgg tcaccataat tgtggttgcc ttccttgcgt ctatcaaact ttgtattcaa 30360 ctttgcggtt tatgtaatac tttggtgctg tccccttcta tttatttgta tgataggagt 30420 aagcagcttt ataagtacta taatgaagaa atgagactgc ccctattaga ggtggatgat 30480 atctaatcca aacattatga gtagtactac tcaggcccca gagcccgtct atcaatggac 30540 cgccgacgag gcagttcaat tccttaagga atggaacttc tcgttgggca ttatactact 30600 ctttattact atcatactac agttcggtta cacgagccgt agcatgttta tttatgttgt 30660 gaaaatgata atcttgtggt taatgtggcc actgactatt gttttgtgta ttttcaattg 30720 cgtgtatgcg ctaaataatg tgtatcttgg attttctata gtgtttacta tagtgtccat 30780 tgtaatctgg atcatgtatt ttgtgaacag cataaggttg tttatcagga ctggtagctg 30840 gtggagcttc aaccccgaaa caaacaacct tatgtgtata gatatgaaag gtaccgtgta 30900 tgttagaccc attattgagg attaccatac actaacagcc actattattc gtggccacct 30960 ctacatgcaa ggtgttaagc taggcaccgg tttctctttg tctgacttgc ccgcttatgt 31020 tacagttgct aaggtgtcac acctttgcac ttataagcgc gcattcttag acaaggtaga 31080 cggtgttagc ggttttgctg tttatgtgaa gtccaaggtc ggaaattacc gactgccctc 31140 aaacaaaccg agtggcgcgg acaccgcatt gttgagaacc taatctaaac tttaaggaga 31200 gaatgaatcc tatgtcggcg ctcggtggta acccctcgcg agaaagtcgg gataggacac 31260 tctctatcag aatggatgtc ttgctgtcat aacagataga gaaggttgtg gcagaccctg 31320 tatcaattag ttgaaagaga ttgcaaaata gagaatgtgt gagagaagtt agcaaggtcc 31380 tacgtctaac cataagaacg gcgataggcg ccccctggga acagctcaca tcagggtact 31440 attcctgcaa tgccctagta aatgaatgaa gttgatcatg gccaattgga agaatcacaa 31500 aaaaaaaaaa aaaaacggcc ggtttaaacg ctacagtcca agttccaagc gggatactag 31560 atgtataatg tccgccatgc agacgaaacc agtcggagat taccgagcat tctatcacgt 31620 cggcgaccaa tagtgagctt agggataaca gggtaataaa cgatccccgg gaattcactg 31680 gccgtcgttt tacaacgtcg tgactgggaa aaccctggcg ttacccaact taatcgcctt 31740 gcagcacatc cccctttcgc cagctggcgt aatagcgaag aggcccgcac cgatcgccct 31800 tcccaacagt tgcgcagcct gaatggcgaa tggcgataga tccggtggat gaccttttga 31860 atgaccttta atagattata ttactaatta attggggacc ctagaggtcc ccttttttat 31920 tttaaaaatt ttttcacaaa acggtttaca agcataaagc tcggacggat cttttccgct 31980 gcataaccct gcttcggggt cattatagcg attttttcgg tatatccatc ctttttcgca 32040 cgatatacag gattttgcca aagggttcgt gtagactttc cttggtgtat ccaacggcgt 32100 cagccgggca ggataggtga agtaggccca cccgcgagcg ggtgttcctt cttcactgtc 32160 ccttattcgc acctggcggt gctcaacggg aatcctgctc tgcgaggctg gccggctacc 32220 gccggcgtaa cagatgaggg caagcggatg gctgatgaaa ccaagccaac caggaagggc 32280 agcccaccta tcaaggtgtc gatgcagggg ggggggaaag ccacgttgtg tctcaaaatc 32340 tctgatgtta cattgcacaa gataaaaata tatcatcatg aacaataaaa ctgtctgctt 32400 acataaacag taatacaagg ggtgttatga gccatattca acgggaaacg tcttgctcaa 32460 ggccgcgatt aaattccaac atggatgctg atttatatgg gtataaatgg gctcgcgata 32520 atgtcgggca atcaggtgcg acaatctatc gattgtatgg gaagcccgat gcgccagagt 32580 tgtttctgaa acatggcaaa ggtagcgttg ccaatgatgt tacagatgag atggtcagac 32640 taaactggct gacggaattt atgcctcttc cgaccatcaa gcattttatc cgtactcctg 32700 atgatgcatg gttactcacc actgcgatcc ccggaaaaac agcattccag gtattagaag 32760 aatatcctga ttcaggtgaa aatattgttg atgcgctggc agtgttcctg cgccggttgc 32820 attcgattcc tgtttgtaat tgtcctttta acagcgatcg cgtatttcgt ctcgctcagg 32880 cgcaatcacg aatgaataac ggtttggttg atgcgagtga ttttgatgac gagcgtaatg 32940 gctggcctgt tgaacaagtc tggaaagaaa tgcataagtt tttgccattc tcaccggatt 33000 cagtcgtcac tcatggtgat ttctcacttg ataaccttat ttttgacgag gggaaattaa 33060 taggttgtat tgatgttgga cgagtcggaa tcgcagaccg ataccaggat cttgccatcc 33120 tatggaactg cctcggtgag ttttctcctt cattacagaa acggcttttt caaaaatatg 33180 gtattgataa tcctgatatg aataaattgc agtttcattt gatgctcgat gagtttttct 33240 aatcagaatt ggttaattgg ttgtaacact ggcagagcat tacgctgact tgacgggacg 33300 gcggctttgt tgaataaatc gaacttttgc tgagttgaag gatcagatca cgcatcttcc 33360 cgacaacgca gaccgttccg tggcaaagca aaagttcaaa atcaccaact ggtccaccta 33420 caacaaagct ctcatcaacc gtggctccct cactttctgg ctggatgatg gggcgattca 33480 ggcctggtat gagtcagcaa caccttcttc acgaggcaga cctcagacgg tatcggatcg 33540 atcccccgat gtgtagcagt ggcggaccat ataggcagat cagaaggcgc ggttctccta 33600 catgagcttt tcaattcaat tcatcatttt ttttttattc ttttttttga tttcggtttc 33660 cttgaaattt ttttgattcg gtaatctccg aacagaagga agaacgaagg aaggagcaca 33720 gacttagatt ggtatatata cgcatatgta gtgttgaaga aacatgaaat tgcccagtat 33780 tcttaaccca actgcacaga acaaaaacct gcaggaaacg aagataaatc atgtcgaaag 33840 ctacatataa ggaacgtgct gctactcatc ctagtcctgt tgctgccaag ctatttaata 33900 tcatgcacga aaagcaaaca aacttgtgtg cttcattgga tgttcgtacc accaaggaat 33960 tactggagtt agttgaagca ttaggtccca aaatttgttt actaaaaaca catgtggata 34020 tcttgactga tttttccatg gagggcacag ttaagccgct aaaggcatta tccgccaagt 34080 acaatttttt actcttcgaa gacagaaaat ttgctgacat tggtaataca gtcaaattgc 34140 agtactctgc gggtgtatac agaatagcag aatgggcaga cattacgaat gcacacggtg 34200 tggtgggccc aggtattgtt agcggtttga agcaggcggc agaagaagta acaaaggaac 34260 ctagaggcct tttgatgtta gcagaattgt catgcaaggg ctccctatct actggagaat 34320 atactaaggg tactgttgac attgcgaaga gcgacaaaga ttttgttatc ggctttattg 34380 ctcaaagaga catgggtgga agagatgaag gttacgattg gttgattatg acacccggtg 34440 tgggtttaga tgacaaggga gacgcattgg gtcaacagta tagaaccgtg gatgatgtgg 34500 tctctacagg atctgacatt attattgttg gaagaggact atttgcaaag ggaagggatg 34560 ctaaggtaga gggtgaacgt tacagaaaag caggctggga agcatatttg agaagatgcg 34620 gccagcaaaa ctaaaaaact gtattataag taaatgcatg tatactaaac tcacaaatta 34680 gagcttcaat ttaattatat cagttattac ccgggaatct cggtcgtaat gatttttata 34740 atgacgaaaa aaaaaaaatt ggaaagaaaa agctgggcgc gccggccggc ccttttcatc 34800 acgtgctata aaaataatta taatttaaat tttttaatat aaatatataa attaaaaata 34860 gaaagtaaaa aaagaaatta aagaaaaaat agtttttgtt ttccgaagat gtaaaagact 34920 ctagggggat cgccaacaaa tactaccttt tatcttgctc ttcctgctct caggtattaa 34980 tgccgaattg tttcatcttg tctgtgtaga agaccacaca cgaaaatcct gtgattttac 35040 attttactta tcgttaatcg aatgtatatc tatttaatct gcttttcttg tctaataaat 35100 atatatgtaa agtacgcttt ttgttgaaat tttttaaacc tttgtttatt tttttttttc 35160 ttcattccgt aactcttcta ccttctttat ttactttcta aaatccaaat acaaaacata 35220 aaaataaata aacacagagt aaattcccaa attattccat cattaaaaga tacgaggcgc 35280 gtgtaagtta caggcaagcg atcggccggc ccgggcattt aaatgcaggc cgcgtacgcg 35340 tcgacggtac cgaattcgct taaacgagct catgttcgcc ggtgaacgcg ttgaggaagc 35400 cgggcagtgc ctcggcaaaa tccttgcgtg tagacaagac atctgcgtag cagttgtcct 35460 caacaacgat gtcgaaatcc aaatcggagt gctcatcgag tcctccgtga acgtaagagc 35520 cgccgatcag aagagcgcgg aagcgaacat cggaagcgac cgcatcgcgg atgcggttca 35580 agaaagttgc atgagcttgt ggaagtgtgc tgagcataaa tgattctcct agctgttctt 35640 tgggtaagta cgccatcagg acgttgtgag tggcgcgatt tttagcggct gaaatcagcc 35700 cttgagcctg tcggcaagtc gcgtcatgag gtccatgcgc tcatgcagga tcgccacgac 35760 caacgcgggt tcgcccgcac gcggcaggca aaaaacgtag tggtgttcgc agcgggccat 35820 ccgcagcgcg ggaaagagtt cgctcatgtc cttaaacggg ccttcgccgg cggcaagcct 35880 ggctatgccc tgttccagct tagcgatata gcggcgcacc tgcgccgcgc cccactcccg 35940 gcgcgtgtag cggatgatgc cgcgtagatc ggcttcggcc tcagccgtga ggatgtaggc 36000 cgtcaagcgc gatccccgct gagttcttca tcaagaattt cgccgacgct cttggtggac 36060 accttgccgg caagcccatc gttgatgcgg ttccccagca tggttttcag ttcctgccat 36120 gcctgatcgg catcagcgtc accggggaac agacgttcga gggcgtattg cttaatggtc 36180 ttgccctgca aggcggccag ggctttcagg ctctggtgct gctggtccgt catgtcgatt 36240 gtcaggcggc tcattggata acctccataa aatacacgta accacattag cacatatgtg 36300 ggcgtgaggc tacagcgcga ggcgcattaa ggtcgggaaa atgcgctagg cgcatttaaa 36360 ttgcgtattg ctgtaatgcg ccatgccggc tagactaggc ccaaatgggt atacccaatt 36420 tgaccaaggg ggacgcgatg agggcggcca agcactaccg acaacttcta tccatcgact 36480 tcaacatcga ggcgctggcc ttcgtgcctg gacccgacgg cacacgcggc cggcgcatcc 36540 acgtcctggg gcgcgaggtc cgcgaccggc ccggcctggt cgagtacctt tcgccggcgt 36600 tcggctcgcg ggtggcgctg gacggctact gcaaggccaa tttcgatgca gtgctgcacc 36660 tggcgtaccc cgatcatcag caatggggcc acgcatgaag cgccgaagct acgccatgct 36720 gcgcgccgct gccgcgctgg ccgtcctggt cgttgcctcg ccggcatggg ccgagctgcg 36780 cggcgaggtc gtgcgcatca tcgacggcga caccatcgac gtgctggtag acaagcagcc 36840 ggtgcgcgtg cgcctggtgg acattgacgc gccggaaaag cggcaagcct tcggcgaacg 36900 tgcgcgccag gcgctggccg gcatggtgtt ccgccggcac gtcctggtcg acgagaagga 36960 caccgaccgt tacggccgca cgctgggcac cgtgtgggtc aacatggagc tggccagccg 37020 gccgccgcag ccgcgcaacg tcaacgccgc gatggttcac cagggcatgg cgtgggccta 37080 tcgcttccac ggccgcgcgg ccgaccctga aatgctgcgg ctcgaacagg aggcgcgagg 37140 caagcgcgtc ggcctctggt ccgatccgca cgccgtcgag ccgtggaaat ggcgacgcga 37200 gagcaacaac cggagggacg aaggttgaag gtcgcccgca tctacctgcg cgccagtacg 37260 gacgagcaga atcttgaacg ccaggagagc cttgtagcgg ccacgcgggc cgccgggtac 37320 tacgtcgccg gcatctaccg cgagaaggcg tccggcgcac gcgccgaccg gcccgagctg 37380 ctgcgcatga tcgcggacct gcaacctggt gaagtcgtcg ttgcggagaa gatcgaccgc 37440 atcagccgct tgccgttggc cgaggccgag cgcctggttg cgtcgatccg ggccaaaggg 37500 gccaagctgg ccgtgcctgg cgtggtggac ctgtcggagc tggccgccga ggcgaacgga 37560 gtggcgaaaa tcgttctgga atccgtccag gacatgcttt tgaagctcgc cttgcagatg 37620 gcccgcgacg actacgagga tcggcgcgag cgtcaacgtc agggtgtcca gttggcgaag 37680 gccgccggcc gctacaccgg ccgcaaacgt gacgccggca tgcacgaccg catcatcacg 37740 cttcgctccg gcggatcgag cattgccaag acggccaagc tggtcggatg cagcccgagc 37800 caggtcaaac gagtgtgggc ggcctggaac gcgcagcagc aaaaataaag ccgggcagtg 37860 cccggctttt ctcacctttt cgcgtcccgc agggccgctg cgagcgccct acctagatcc 37920 tcgctttccc cctcggtgta gtccggccag ggcacgaagg gcgcggatgc gaacctgttg 37980 agcaggtacg ccttcgggca gcggtagacc accggcgagt tcgccttttc atcccaccgg 38040 gccaggatca cgtccgcatc acagtgcatg tccttcacct ggtcgcggaa gaagccgaag 38100 gccaccatgc cgctatgttc gccgaggaac gccagttgct tcgcgctggc gatcgcgccg 38160 acgccgccgg ccaaaaccga cgccatcacc cagccgacga accagaagct ggcatgcttg 38220 cggttgacca ccgcacgcgc agccgcgacc aggacaacgg ccaagctgcc gaccagggcc 38280 atgacgaccg tgatccggcc gttgtggaaa gcgatgggct tgccagcgtc cgcttgcacg 38340 gcgtcgtaaa tgctggaccc gatgggcgcg cacatcagca cgacaggcag cagcaccagg 38400 aacatcgtcc gcgtccattg cgcgagtgcc ttgcggcgtt cgccggcggc aagcgcctcc 38460 atcatcggcg tgaagcccaa cagggccacc gcagccgcca agccggcaac gatgccgcag 38520 gcgattacat acatacatcc tccctaatgc gccttgcgca cggttgtagt cagagtccgc 38580 ggtggggcga taagctcatg accaaaatcc cttaacgtga gttttcgttc cactgagcgt 38640 cagaccccgt agaaaagatc aaaggatctt cttgagatcc tttttttctg cgggggatca 38700 ggaccgctgc cggagcgcaa cccactcact acagcagagc catgtagaca acatcccctc 38760 cccctttcca ccgcgtcaga cgcccgtagc agcccgctac gggctttttc atgccctgcc 38820 ctagcgtcca agcctcacgg ccgcgctcgg cctctctggc ggccttctgg cgctcctgct 38880 gcggcgtccg ctcgtgggcc gtggcgcggg tccgcgcgcc ggcctcgtgc gcctggcgct 38940 cgcgggcgag gtccagggcg gccgtcttca cgttctgcct tgcgcagatg agatagatcg 39000 atctagcgtg gactcaaggc tctcgcgaat ggctcgcgtt ggaaactttc attgacactt 39060 gaggggcacc gcagggaaat tctcgtcctt gcgagaaccg gctatgtcgt gctgcgcatc 39120 gagcctgcgc ccttggcttg tctcgcccct ctccgcgtcg ctacggggct tccagcgcct 39180 ttccgacgct caccgggctg gttgccctcg ccgctgggct ggcggccgtc tatggccctg 39240 caaacgcgcc agaaacgccg tcgaagccgt gtgcgagaca ccgcggccgc cggcgttgtg 39300 gatacctcgc ggaaaacttg gccctcactg acagatgagg ggcggacgtt gacacttgag 39360 gggccgactc acccggcgcg gcgttgacag atgaggggca ggctcgattt cggccggcga 39420 cgtggagctg gccagcctcg caaatcggcg aaaacgcctg attttacgcg agtttcccac 39480 agatgatgtg gacaagcctg gggataagtg ccctgcggta ttgacacttg aggggcgcga 39540 ctactgacag atgaggggcg cgatccttga cacttgaggg gcagagtgct gacagatgag 39600 gggcgcacct attgacattt gaggggctgt ccacaggcag aaaatccagc atttgcaagg 39660 gtttccgccc gtttttcggc caccgctaac ctgtctttta acctgctttt aaaccaatat 39720 ttataaacct tgtttttaac cagggctgcg ccctgtgcgc gtgaccgcgc acgccgaagg 39780 ggggtgcccc cccttctcga accctcccgg cccgctaacg cgggcctccc atccccccag 39840 gggctgcgcc cctcggccgc gaacggcctc accccaaaaa tggcagcgct ggcagtcctt 39900 gccattgccg ggatcggggc agtaacggga tgggcgatca gcccgagcgc gacgcccgga 39960 agcattgacg tgccgcaggt gctggcatcg acattcagcg accaggtgcc gggcagtgag 40020 ggcggcggcc tgggtggcgg cctgcccttc acttcggccg tcggggcatt cacggacttc 40080 atggcggggc cggcaatttt taccttgggc attcttggca tagtggtcgc gggtgccgtg 40140 ctcgtgttcg ggggtgaatt aattccccgg atcgatccgt cagcttcacg ctgccgcaag 40200 cactcagggc gcaagggctg ctaaaggaag cggaacacgt agaaagccag tccgcagaaa 40260 cggtgctgac cccggatgaa tgtcagctac tgggctatct ggacaaggga aaacgcaagc 40320 gcaaagagaa agcaggtagc ttgcagtggg cttacatggc gatagctaga ctgggcggtt 40380 ttatggacag caagcgaacc ggaattgcca gctggggcgc cctctggtaa ggttgggaag 40440 ccctgcaaag taaactggat ggctttcttg ccgccaagga tctgatggcg caggggatca 40500 agatcgacgg atcgatccgg ggaattaatt ccggggcaat cccgcaagga gggtga 40556 <210> 40 <211> 38383 <212> DNA <213> Artificial Sequence <220> <223> pMR10Y_COVAX191_delHEN <400> 40 atgaatcgga cgtttgaccg gaaggcatac aggcaagaac tgatcgacgc ggggttttcc 60 gccgaggatg ccgaaaccat cgcaagccgc accgtcatgc gtgcgccccg cgaaaccttc 120 cagtccgtcg gctcgatggt ccagcaagct acggccaaga tcgagcgcga cagcgtgcaa 180 ctggctcccc ctgccctgcc cgcgccatcg gccgccgtgg agcgttcgcg tcgtctcgaa 240 caggaggcgg caggtttggc gaagtcgatg accatcgaca cgcgaggaac tatgacgacc 300 aagaagcgaa aaaccgccgg cgaggacctg gcaaaacagg tcagcgaggc caagcaggcc 360 gcgttgctga aacacacgaa gcagcagatc aaggaaatgc agctttcctt gttcgatatt 420 gcgccgtggc cggacacgat gcgagcgatg ccaaacgaca cggcccgctc tgccctgttc 480 accacgcgca acaagaaaat cccgcgcgag gcgctgcaaa acaaggtcat tttccacgtc 540 aacaaggacg tgaagatcac ctacaccggc gtcgagctgc gggccgacga tgacgaactg 600 gtgtggcagc aggtgttgga gtacgcgaag cgcaccccta tcggcgagcc gatcaccttc 660 acgttctacg agctttgcca ggacctgggc tggtcgatca atggccggta ttacacgaag 720 gccgaggaat gcctgtcgcg cctacaggcg acggcgatgg gcttcacgtc cgaccgcgtt 780 gggcacctgg aatcggtgtc gctgctgcac cgcttccgcg tcctggaccg tggcaagaaa 840 acgtcccgtt gccaggtcct gatcgacgag gaaatcgtcg tgctgtttgc tggcgaccac 900 tacacgaaat tcatatggga gaagtaccgc aagctgtcgc cgacggcccg acggatgttc 960 gactatttca gctcgcaccg ggagccgtac ccgctcaagc tggaaacctt ccgcctcatg 1020 tgcggatcgg attccacccg cgtgaagaag tggcgcgagc aggtcggcga agcctgcgaa 1080 gagttgcgag gcagcggcct ggtggaacac gcctgggtca atgatgacct ggtgcattgc 1140 aaacgctagg gccttgtggg gtcagttccg gctgggggtt cagcagccac tcgatcgagg 1200 tcccaatacg caaaccgcct ctccccgcgc gttggccgat tcattaatgc agctggcacg 1260 acaggtttcc cgactggaaa gcgggcagtg agcgcaacgc aattaatgtg agttagctca 1320 ctcattaggc accccaggct ttacacttta tgcttccggc tcgtatgttg tgtggaattg 1380 tgagcggata acaatttcac acaggaaaca gctatgacca tgattacgcc aagcttccat 1440 gggatatcga gatctcctgc agagctctag agtcgagact agtctcgacg ggcccggtac 1500 cccctcgagg gggccgcact taagttacgc gtggatcgtg gagctttcgg gttttaacta 1560 taacggtcct aaggtagcga actcgggtct tgccttaatc ccaacaaccg gattatctac 1620 acggatttca atagctgata tagcgaatca ccgagattaa ttaataatac gactcactat 1680 agtataagag tgattggcgt ccgtacgtac cctctcaact ctaaaactct tgtagtttaa 1740 atctaatcta aactttataa acggcacttc ctgcgtgtcc atgcccgcgg gcctggtctt 1800 gtcatagtgc tgacatttgt agttccttga ctttcgttct ctgccagtga cgtgtccatt 1860 cggcgccagc agcccaccca taggttgcat aatggcaaag atgggcaaat acggcctggg 1920 cttcaaatgg gccccagaat ttccatggat gcttccgaac gcatcggaga agttgggtaa 1980 ccctgagagg tcagaggagg atgggttttg cccctctgct gcgcaagaac cgaaagttaa 2040 aggaaaaact ttggttaatc acgtgagggt gaattgtagc cggcttccag ctttggaatg 2100 ctgtgttcag tctgccataa tccgtgatat ttttgtagat gaggatcccc agaaggtgga 2160 ggcctcaact atgatggcat tgcagttcgg tagtgccgtc ttggttaagc catccaagcg 2220 cttgtctatt caggcatgga ctaatttggg tgtgcttccc aaaacagctg ccatggggtt 2280 gttcaagcgc gtctgcctgt gtaacaccag ggagtgctct tgtgacgccc acgtggcctt 2340 tcaccttttt acggtccaac ccgatggtgt atgcctgggt aatggccgtt ttataggctg 2400 gttcgttcca gtcacagcca taccggagta tgcgaagcag tggttgcaac cctggtccat 2460 ccttcttcgt aagggtggta acaaagggtc tgtgacatcc ggccacttcc gccgcgctgt 2520 taccatgcct gtgtatgact ttaatgtaga ggatgcttgt gaggaggttc atcttaaccc 2580 gaagggtaag tactcctgca aggcgtatgc cctgctgaag ggctatcgcg gtgttaagcc 2640 catcctgttt gtggaccagt atggttgcga ctatactgga tgtctcgcca agggtcttga 2700 ggactatggc gatctcacct tgagtgagat gaaggagttg ttccctgtgt ggcgtgactc 2760 cttggatagt gaagtccttg tggcttggca cgttgatcga gatcctcggg ctgctatgcg 2820 tctgcagact cttgctactg tacgttgcat tgattatgtg ggccaaccga ccgaggatgt 2880 ggtggatgga gatgtggtag tgcgtgagcc tgctcatctt ctcgcagcca atgccattgt 2940 taaaagactc ccccgtttgg tggagactat gctgtatacg gattcgtccg ttacagaatt 3000 ctgttataaa accaagctgt gtgaatgcgg ttttatcacg cagtttggct atgtggattg 3060 ttgtggtgac acctgtgatt ttcgtgggtg ggttgccggc aatatgatgg atggctttcc 3120 atgtccaggg tgtaccaaaa attatatgcc ctgggaattg gaggcccagt catcaggtgt 3180 tataccagaa ggaggtgttc tattcactca gagcactgat acagtgaatc gtgagtcctt 3240 taagctctac ggtcatgctg ttgtgccttt tggttctgct gtgtattgga gcccttgccc 3300 aggtatgtgg cttccagtaa tttggtcgtc ggttaagtca tactctggtt tgacttatac 3360 aggagtagtt ggttgtaagg caattgttca agagacagac gctatatgtc gttctctgta 3420 tatggattat gtccagcaca agtgtggcaa tctcgagcag agagctatcc ttggattgga 3480 cgatgtctat catagacagt tgcttgtgaa taggggtgac tatagtctcc tccttgagaa 3540 tgtggatttg tttgttaagc ggcgcgctga atttgcttgc aaattcgcca cctgtggaga 3600 tggtcttgta cccctcctac tagatggttt agtgccccgc agttattatt tgattaagag 3660 tggtcaagct ttcacctcta tgatggttaa ttttagccat gaggtgactg acatgtgtat 3720 ggacatggct ttattgttca tgcatgatgt taaagtggcc actaagtatg ttaagaaggt 3780 tactggcaaa ctggccgtgc gctttaaagc gttgggtgta gccgttgtca gaaaaattac 3840 tgaatggttt gatttagccg tggacattgc tgctagtgcc gctggatggc tttgctacca 3900 gctggtaaat ggcttatttg cagtggccaa tggtgttata acctttgtac aggaggtgcc 3960 tgagcttgtc aagaattttg ttgacaagtt caaggcattt ttcaaggttt tgatcgactc 4020 tatgtcggtt tctatcttgt ctggacttac tgttgtcaag actgcctcaa atagggtgtg 4080 tcttgctggc agtaaggttt atgaagttgt gcagaaatct ttgtctgcat atgttatgcc 4140 tgtgggttgc agcgaagcca cttgtttggt gggtgagatt gaacctgcag tttttgaaga 4200 tgatgttgtt gatgtggtta aagccccatt aacatatcaa ggctgttgta agccacccac 4260 ttctttcgag aagatttgta ttgtggataa attgtatatg gccaagtgtg gtgatcaatt 4320 ttaccctgtg gttgttgata acgacactgt tggcgtgtta gatcagtgct ggaggtttcc 4380 ctgtgcgggc aagaaagtcg agtttaacga caagcccaaa gtcaggaaga taccctccac 4440 ccgtaagatt aagatcacct tcgcactgga tgcgaccttt gatagtgttc tttcgaaggc 4500 gtgttcagag tttgaagttg ataaagatgt tacattggat gagctgcttg atgttgtgct 4560 tgacgcagtt gagagtacgc tcagcccttg taaggagcat gatgtgatag gcacaaaagt 4620 ttgtgcttta cttgataggt tggcaggaga ttatgtctat ctttttgatg agggaggcga 4680 tgaagtgatc gccccgagga tgtattgttc cttttctgct cctgatgacg aggactgcgt 4740 tgcagcggat gttgtagatg cagatgaaaa ccaagatgat gatgccgagg actcagcagt 4800 ccttgtcgct gatacccaag aagaggacgg cgttgccaag gggcaggttg aggcggattc 4860 ggaaatttgc gttgcgcata ctggtagtca agaagaattg gctgagcctg atgctgtcgg 4920 atctcaaact cccatcgcct ctgctgagga aaccgaagtc ggagaggcaa gcgacaggga 4980 agggattgct gaggcgaagg caactgtgtg tgctgatgct gtagatgcct gccccgatca 5040 agtggaggca tttgaaattg aaaaggtcga ggactctatc ttggatgagc ttcaaactga 5100 acttaatgcg ccagcggaca agacctatga ggatgtcttg gcattcgatg ccgtatgctc 5160 agaggcgttg tctgcattct atgctgtgcc gagtgatgag acgcacttta aagtgtgtgg 5220 attctattcg cctgctatag agcgcactaa ttgttggctg cgttctactt tgatagtaat 5280 gcagagtcta cctttggaat ttaaagactt ggagatgcaa aagctctggt tgtcttacaa 5340 ggccggctat gaccaatgct ttgtggacaa actagttaag agcgtgccca agtctattat 5400 ccttccacaa ggtggttatg tggcagattt tgcctatttc tttctaagcc agtgtagctt 5460 taaagcttat gctaactggc gttgtttaga gtgtgacatg gagttaaagc ttcaaggctt 5520 ggacgccatg tttttctatg gggacgttgt gtctcatatg tgcaagtgtg gtaatagcat 5580 gaccttgttg tctgcagata taccctacac tttgcatttt ggagtgcgag atgataagtt 5640 ttgcgctttt tacacgccaa gaaaggtctt tagggctgct tgtgcggtag atgttaatga 5700 ttgtcactct atggctgtag tagagggcaa gcaaattgat ggtaaagtgg ttaccaaatt 5760 tattggtgac aaatttgatt ttatggtggg ttacgggatg acatttagta tgtctccttt 5820 tgaactcgcc cagttatatg gttcatgtat aacaccaaat gtttgttttg ttaaaggaga 5880 tgttataaag gttgttcgct tagttaatgc tgaagtcatt gttaaccctg ctaatgggcg 5940 tatggctcat ggtgccggcg tcgccggcgc catagctgaa aaggcgggca gtgcttttat 6000 taaagaaacc tccgatatgg tgaaggctca gggcgtttgc caggttggtg aatgctatga 6060 atctgccggt ggtaagttat gtaaaaaggt gcttaacatt gtagggccag atgcgcgagg 6120 gcatggcaag caatgctatt cacttttaga gcgtgcttat cagcatatta ataagtgtga 6180 caatgttgtc actactttaa tttcggctgg tatatttagt gtgcctactg atgtctccct 6240 aacttactta cttggtgtag tgacaaagaa tgtcattctt gtcagtaaca accaggatga 6300 ttttgatgtg atagagaagt gtcaggtgac ctccgttgct ggtaccaaag cgctatcact 6360 tcaattggcc aaaaatttgt gccgtgatgt aaagtttgtg acgaatgcat gtagttcgct 6420 ttttagtgaa tcttgctttg tctcaagcta tgatgtgttg caggaagttg aagcgctgcg 6480 acatgatata caattggatg atgatgctcg tgtctttgtg caggctaata tggactgtct 6540 gcccacagac tggcgtctcg ttaacaaatt tgatagtgtt gatggtgtta gaaccattaa 6600 gtattttgaa tgcccgggcg ggatttttgt atccagccag ggcaaaaagt ttggttatgt 6660 tcagaatggt tcatttaagg aggcgagtgt tagccaaata agggctttac tcgctaataa 6720 ggttgatgtc ttgtgtactg ttgatggtgt taacttccgc tcctgctgcg tagcagaggg 6780 tgaagttttt ggcaagacat taggttcagt cttttgtgat ggcataaatg tcaccaaagt 6840 taggtgtagt gccatttaca agggtaaggt tttctttcag tacagtgatt tgtccgaggc 6900 agatcttgtg gctgttaaag atgcctttgg ttttgatgaa ccacaactgc tgaagtacta 6960 cactatgctt ggcatgtgta agtggccagt agttgtttgt ggcaattatt ttgctttcaa 7020 gcagtcaaat aataattgct acatcaacgt ggcatgttta atgctgcaac acttgagttt 7080 aaagtttcct aagtggcaat ggcaagaggc ttggaacgag ttccgctctg gtaaaccact 7140 aaggtttgtg tccttggtat tagcaaaggg cagctttaaa tttaatgaac cttctgattc 7200 tatcgatttt atgcgtgtgg tgctacgtga agcagatttg agtggtgcca cgtgcaattt 7260 ggaatttgtt tgtaaatgtg gtgtgaagca agagcagcgc aaaggtgttg acgctgttat 7320 gcattttggt acgttggata aaggtgatct tgtcaggggt tataatatcg catgtacgtg 7380 cggtagtaaa cttgtgcatt gcacccaatt taacgtacca tttttaattt gctccaacac 7440 accagagggt aggaaactgc ccgacgatgt tgttgcagct aatattttta ctggtggtag 7500 tgtgggccat tacacgcatg tgaaatgtaa acccaagtac cagctttatg atgcttgtaa 7560 tgttaataag gtttcggagg ctaagggtaa ttttaccgat tgcctctacc ttaaaaattt 7620 aaagcaaacc ttctcgtctg tgctgacgac tttttattta gatgacgtaa agtgtgtgga 7680 gtataagcca gatttatcgc agtattactg tgagtctggt aaatattata caaaacccat 7740 tattaaggcc caatttagaa catttgagaa ggttgatggt gtctatacca actttaaatt 7800 ggtgggacat agtattgctg aaaaactcaa tgctaagctg ggatttgatt gtaattctcc 7860 ctttgtggag tacaaaatta cagagtggcc aacagctact ggagatgtgg tgttggctag 7920 tgatgatttg tatgtaagtc ggtacttaag cgggtgcatt acttttggta aaccggttgt 7980 ctggcttggc catgaggaag catcgctgaa atctctcaca tattttaata gacctagtgt 8040 cgtttgtgaa aataaattta acgtgttgcc cgttgatgtc agtgaaccca cggacaaggg 8100 gcctgtgcct gctgcagtcc ttgttaccgg cgtccctgga gctgatgcgt cagctggtgc 8160 cggtattgcc aaggagcaaa aagcctgtgc ttctgctagt gtggaggatc aggttgttac 8220 ggaggttcgt caagagccat ctgtttcagc tgctgatgtc aaagaggtta aattgaatgg 8280 tgttaaaaag cctgttaagg tggaaggtag tgtggttgtt aatgatccca ctagcgaaac 8340 caaagttgtt aaaagtttgt ctattgttga tgtctatgat atgttcctga cagggtgtaa 8400 gtatgtggtt tggactgcta atgagttgtc tcgactagta aattcaccga ctgttaggga 8460 gtatgtgaag tggggtatgg gaaagattgt aacacccgct aagttgttgt tgttaagaga 8520 tgagaagcaa gagttcgtag cgccaaaagt agtcaaggcg aaagctattg cctgctattg 8580 tgctgtgaag tggtttctcc tctattgttt tagttggata aagtttaata ctgacaataa 8640 ggttatatac accacagaag tagcttcaaa gcttactttc aagttgtgct gtttggcctt 8700 taagaatgcc ttacagacgt ttaattggag cgttgtgtct aggggctttt tcctagttgc 8760 aacggtcttt ttactctggt ttaacttttt gtatgctaat gttattttga gtgacttcta 8820 tttgcctaat attgggcctc tccctacgtt tgtgggacag atagttgcgt ggtttaagac 8880 tacatttggt gtgtcaacca tctgtgattt ctaccaggtg acggatttgg gctatagaag 8940 ttcgttttgt aatggaagta tggtatgtga actatgcttc tcaggttttg atatgctgga 9000 caactatgat gctataaatg ttgttcaaca cgttgtagat aggcgtttgt cctttgacta 9060 tattagccta tttaaactgg tagttgagct tgtaatcggc tactctcttt atactgtgtg 9120 cttctaccca ctgtttgtcc ttattggaat gcagttattg accacatggt tgcctgaatt 9180 ctttatgctg gagactatgc attggagtgc tcgtttgttt gtgtttgttg ccaatatgct 9240 tccagctttt acgttactgc gattttacat cgtggtgaca gctatgtata aggtctattg 9300 tctttgtaga catgttatgt atggatgtag taagcctggt tgcttgtttt gttataagag 9360 aaaccgtagt gtccgtgtta agtgtagcac cgttgttggt ggttcactac gctattacga 9420 tgtaatggct aacggcggca caggtttctg tacaaagcac cagtggaact gtcttaattg 9480 caattcctgg aaaccaggca atacattcat aactcatgaa gcagcggcgg acctctctaa 9540 ggagttgaaa cgccctgtga atccaacaga ttctgcttat tactcggtca cagaggttaa 9600 gcaggttggt tgttccatgc gtttgttcta cgagagagat ggacagcgtg tttatgatga 9660 tgttaatgct agtttgtttg tggacatgaa tggtctgctg cattctaaag ttaaaggtgt 9720 gcctgaaacg catgttgtgg ttgttgagaa tgaagctgat aaagctggtt ttctcggcgc 9780 cgcagtgttt tatgcacaat cgctctacag acctatgttg atggtggaaa agaaattaat 9840 aactaccgcc aacactggtt tgtctgttag tcgaactatg tttgaccttt atgtagattc 9900 attgctgaac gtcctcgacg tggatcgcaa gagtctaaca agttttgtaa atgctgcgca 9960 caactctcta aaggagggtg ttcagcttga acaagttatg gataccttta ttggctgtgc 10020 ccgacgtaag tgtgctatag attctgatgt tgaaaccaag tctattacca agtccgtcat 10080 gtcggcagta aatgctggcg ttgattttac ggatgagagt tgtaataact tggtgcctac 10140 ctatgttaaa agtgacacta tcgttgcagc cgatttgggt gttcttattc agaataatgc 10200 taagcatgta caggctaatg ttgctaaagc cgctaatgtg gcttgcattt ggtctgtgga 10260 tgcttttaac cagctatctg ctgacttaca gcataggctg cgaaaagcat gttcaaaaac 10320 tggcttgaag attaagctta cttataataa gcaggaggca aatgttccta ttttaactac 10380 accgttctct cttaaagggg gcgctgtttt tagtagaatg ttacaatggt tgtttgttgc 10440 taatttgatt tgtttcattg tgttgtgggc ccttatgcca acatatgcag tgcacaaatc 10500 ggatatgcag ttgcctttat atgccagttt taaagttata gataacggtg tgctaaggga 10560 tgtgtctgtt actgacgcat gcttcgcaaa caaatttaat caattcgacc aatggtatga 10620 gtctactttt ggtcttgctt attaccgcaa ctctaaggct tgtcctgttg tggttgctgt 10680 aatagatcaa gacattggcc ataccttatt taatgttcct accacagttt taagatatgg 10740 atttcatgtg ttgcatttta taacccatgc atttgctact gatagcgtgc agtgttacac 10800 gccacatatg caaatcccct atgataattt ctatgctagt ggttgcgtgt tgtcatccct 10860 ctgtactatg cttgcgcatg cagatggaac cccgcatcct tattgttata cagggggtgt 10920 tatgcataat gcctctctgt atagttcttt ggctcctcat gtccgttata acctggctag 10980 ttcaaatggt tatatacgtt ttcccgaagt ggttagtgaa ggcattgtgc gtgttgtgcg 11040 cactcgctct atgacctact gcagggttgg tttatgtgag gaggccgagg agggtatctg 11100 ctttaatttt aatcgttcat gggtattgaa caacccgtat tatagggcca tgcctggaac 11160 tttttgtggt aggaatgctt ttgatttaat acatcaagtt ttaggaggat tagtgcggcc 11220 tattgatttc tttgccttaa cggcgagttc agtggctggt gctatccttg caattattgt 11280 cgttttggct ttctattatt taatcaagct taagcgtgcc tttggtgact acactagtgt 11340 tgtggttatc aatgtaattg tgtggtgtat aaattttctg atgctttttg tgtttcaggt 11400 ttatcccaca ttgtcttgtt tatatgcttg tttctacttc tacaccacgc tttatttccc 11460 ttcggagata agtgttgtta tgcatttgca atggcttgtc atgtatggtg ctattatgcc 11520 cttgtggttt tgcattattt acgtggcagt cgttgtttca aaccatgcat tgtggttgtt 11580 ctcttactgc cgcaaaattg gtaccgaggt tcgtagtgac ggcacatttg aggaaatggc 11640 ccttactacc tttatgatta ctaaagaatc ttattgtaag ttgaaaaact ctgtttctga 11700 tgttgctttt aacaggtact tgagtcttta caacaagtac cgttacttca gtggcaaaat 11760 ggatactgcc gcttatagag aggctgcctg ttcacaactg gcaaaggcaa tggaaacatt 11820 taaccataat aatggtaatg atgttctcta tcagcctcca accgcctctg ttactacatc 11880 atttttacag tctggtatag tgaagatggt gtcgcccacc tctaaagtgg agccttgtat 11940 tgttagtgtt acttatggta acatgacact taatgggttg tggttggatg ataaagttta 12000 ttgcccaaga catgttatct gttcttcagc tgacatgaca gaccctgatt atcctaattt 12060 gctttgtaga gtgacatcaa gtgatttttg tgttatgtct ggtcgtatga gccttactgt 12120 aatgtcttat caaatgcagg gctgccaact tgttttgact gttacactgc aaaatcctaa 12180 cacgcctaag tattccttcg gtgttgttaa gcctggtgag acatttactg tactggctgc 12240 atacaatggc agacctcaag gagccttcca tgttacgctt cgtagtagcc ataccataaa 12300 gggctccttt ctatgtggat cctgcggttc tgtaggatat gttttaactg gcgatagtgt 12360 acgatttgtt tatatgcatc agctagagtt gagtactggt tgtcataccg gtactgactt 12420 tagtgggaac ttttatggtc cctatagaga tgcgcaagtt gtacaattgc ctgttcagga 12480 ttatacgcag actgttaatg ttgtagcttg gctttatgct gctattttta acagatgcaa 12540 ctggtttgtg caaagtgata gttgttccct ggaggagttt aatgtttggg ctatgaccaa 12600 tggttttagc tcaatcaaag ccgatcttgt cttggatgcg cttgcttcta tgacaggcgt 12660 tacagttgaa caggtgttgg ccgctattaa gaggctgcat tctggattcc agggcaaaca 12720 aattttaggt agttgtgtgc ttgaagatga gctgacacca agtgatgttt atcaacaact 12780 agctggtgtc aagctacagt caaagcgcac aagagttata aaaggtacat gttgctggat 12840 attggcttca acgtttttgt tctgtagcat tatctcagca tttgtaaaat ggactatgtt 12900 tatgtatgtt actacccata tgttgggagt gacattgtgt gcactttgtt ttgtaagctt 12960 tgctatgttg ttgatcaagc ataagcattt gtatttaact atgtacatca tgcctgtgtt 13020 atgcacactg ttttacacca actatttggt tgtgtacaaa cagagtttta gaggtctagc 13080 ttatgcttgg ctttcacact ttgtccctgc tgtagattat acatatatgg atgaagtttt 13140 atatggtgtt gtgttgctag tagctatggt gtttgttacc atgcgtagca taaaccacga 13200 cgtcttttct attatgttct tggttggtag acttgtcagc ctggtatcca tgtggtattt 13260 tggagccaat ttagaggaag aggtactatt gttcctcaca tccctatttg gcacgtacac 13320 atggactact atgttgtcat tggctaccgc taaggttatt gctaaatggt tggctgtgaa 13380 tgtcttgtac ttcacagacg taccgcaaat taaattagtt ctgttgagct acttgtgtat 13440 tggttatgtg tgttgttgtt attggggaat cttgtcactc cttaatagca tttttaggat 13500 gccattgggc gtctacaatt ataaaatctc cgttcaggag ttacgttata tgaatgctaa 13560 tggcttgcgc ccacctagaa atagttttga ggccctgatg cttaatttta agctgttggg 13620 aattggtggt gtgccagtca ttgaagtatc tcaaattcaa tcaagattga cggatgttaa 13680 atgtgctaat gttgtgttgc ttaattgcct ccagcacttg catattgcat ctaattctaa 13740 gttgtggcag tattgtagta ctttgcacaa tgaaatactg gctacatctg atttgagcgt 13800 ggccttcgat aagttggctc aactcttagt tgttttattt gctaatccag cagcagtgga 13860 tagcaagtgc cttgcaagta ttgaagaagt gagcgatgat tacgttcgcg acaatactgt 13920 cttgcaagcc ttacagagtg aatttgttaa tatggctagc ttcgttgagt atgaacttgc 13980 taagaagaat ctagatgagg ctaaggctag cggctctgcc aatcaacagc agattaagca 14040 gctagagaag gcgtgtaata ttgctaagtc agcatatgag cgcgacagag ctgttgctcg 14100 taagctggaa cgtatggctg atttagctct tacaaacatg tataaagaag ctagaattaa 14160 tgataagaag agtaaggtag tgtctgcatt gcaaaccatg ctctttagta tggtgcgtaa 14220 gctagataac caagctctta attctatttt agacaacgca gttaagggtt gtgtaccttt 14280 gaatgcaata ccatcattga cttcgaacac tctgactata atagtgccag ataagcaggt 14340 ttttgatcag gttgtggata atgtgtatgt cacctatgct gggaatgtat ggcatataca 14400 gtttattcaa gatgctgatg gtgctgttaa acaattgaat gagatagatg ttaattcaac 14460 ctggcctcta gtcattgctg caaataggca taatgaagtg tctactgttg ttttgcagaa 14520 caatgagttg atgcctcaga agttgagaac tcaggttgtc aatagtggct cagatatgaa 14580 ttgtaatact cctacccagt gttactataa tactactggc acgggtaaga ttgtgtatgc 14640 tatacttagt gactgtgacg gcctgaagta cactaagata gtaaaagaag atggaaattg 14700 tgttgttttg gaattggatc ctccctgtaa gttttctgtt caggatgtga agggccttaa 14760 aattaagtac ctttactttg tgaaggggtg taatacactg gctagaggct gggttgtagg 14820 caccttatcc tcgacagtga gattgcaggc gggtacggca actgagtatg cctccaactc 14880 tgcaatactg tcgctgtgtg cgttttctgt agatcctaag aaaacgtact tggattatat 14940 aaaacagggt ggagttcccg ttactaattg tgttaagatg ttatgtgacc atgctggcac 15000 tggtatggcc attactatta agccggaggc aaccactaat caggattctt atggtggtgc 15060 ttccgtttgt atatattgcc gctcgcgtgt tgaacatcca gatgttgatg gattgtgcaa 15120 attacgcggc aagtttgtcc aagtgccctt aggcataaaa gatcctgtgt catatgtgtt 15180 gacgcatgat gtttgtcagg tttgtggctt ttggcgagat ggtagctgtt cctgtgtagg 15240 cacaggctcc cagtttcagt caaaagacac gaacttttta aacggattcg gggtacaagt 15300 gtaaatgccc gtcttgtacc ctgtgccagt ggcttggaca ctgatgttca attaagggca 15360 tttgacattt gtaatgctaa tcgagctggc attggtttgt attataaagt gaattgctgc 15420 cgcttccagc gtgtagatga ggacggcaac aagttggata agttctttgt tgttaaaaga 15480 actaatttag aagtgtataa caaggagaaa gaatgctatg agttgacaaa agaatgcggt 15540 gttgtggctg aacacgagtt cttcacattt gatgtggagg gaagtcgggt accacacata 15600 gtccgtaaag atctttcaaa gtttactatg ttagatcttt gctatgcatt gcgtcatttt 15660 gaccgcaatg attgttcaac tcttaaggaa attctcctta catatgctga gtgtgaagag 15720 tcctacttcc aaaagaagga ctggtatgat tttgttgaga atcctgatat aattaatgtg 15780 tacaagaagc ttggtcctat atttaataga gccctgctta acactgccaa gtttgcagac 15840 gcattagtgg aggcaggctt agtaggtgtt ttaacacttg ataatcaaga tttatatggt 15900 caatggtatg actttggaga ttttgtcaag acagtacctg gttgtggtgt tgccgtggca 15960 gactcttatt attcatatat gatgccaatg ctgactatgt gtcatgcgtt ggatagtgag 16020 ttgtttgtta atggtactta tagggagttt gaccttgttc agtatgattt tactgatttc 16080 aagctagagc tgttcactaa gtattttaag cattggagta tgacctacca cccgaacacc 16140 tgtgagtgcg aggatgacag gtgcattatt cattgcgcca attttaatat acttttcagc 16200 atggtcttac ctaagacctg ttttgggcct cttgttaggc agatatttgt ggatggtgtt 16260 cctttcgttg tgtcgatcgg ttaccattat aaagaattag gtgttgttat gaatatggat 16320 gtggatacac atcgttatcg cttgtctctt aaggacttgc ttttgtatgc tgcagaccct 16380 gcccttcatg tggcgtctgc tagtgcactg cttgatttgc gcacatgttg ttttagcgtt 16440 gcagctatta caagtggcgt aaaatttcaa acagttaaac ctggaaattt taatcaggat 16500 ttctacgagt ttattttgag taaaggcctg cttaaagagg ggagctccgt tgatttgaag 16560 cacttcttct ttacgcagga tggtaatgct gctattactg attacaatta ctacaagtat 16620 aatctaccca ccatggtgga tattaagcag ttgttgtttg ttttagaagt tgttaataag 16680 tacttcgaga tctatgaggg tgggtgtata cccgcaacac aggtcattgt taataattat 16740 gacaagagtg ctggctatcc atttaataaa tttggaaagg ccaggctcta ttatgaggca 16800 ttatcatttg aggagcagga tgaaatttat gcgtatacca aacgcaatgt cctgccgacc 16860 ctaactcaaa tgaatcttaa atatgctatt agtgctaaga atagggcccg caccgttgct 16920 ggtgtctcta ttctcagtac tatgactggc agaatgtttc atcaaaagtg tctaaagagt 16980 atagcagcta ctcgcggtgt tcctgtagtt ataggcacca cgaagttcta tggcggttgg 17040 gatgatatgt tacgccgcct tattaaagat gttgatagtc ctgtactcat gggttgggac 17100 tatcctaaat gtgatcgtgc tatgccaaac atactgcgta ttgttagtag tttggtgcta 17160 gcccgtaaac atgattcgtg ctgttcgcat acggatagat tctatcgtct tgcgaacgag 17220 tgcgcccaag ttttgagtga aattgttatg tgtggtggtt gttattatgt taaaccaggt 17280 ggcactagta gtggggatgc aaccactgct tttgctaatt ctgtgtttaa catttgtcaa 17340 gctgtttccg ccaatgtatg ctcgcttatg gcatgcaatg gacacaaaat tgaagatttg 17400 agtatacgcg agttacaaaa gcgcctatac tctaatgtct atcgtgcgga ccatgttgac 17460 cccgcatttg ttagtgagta ttatgagttt ttaaacaagc attttagtat gatgattttg 17520 agtgatgatg gtgttgtgtg ttataattca gagtttgcgt ccaagggtta tattgctaat 17580 ataagtgcct ttcaacaggt attatattat caaaacaacg tgtttatgtc tgaggccaaa 17640 tgttgggtag aaacagacat cgaaaaggga ccgcatgaat tttgttctca acatacaatg 17700 ctagtcaaga tggatggtga tgaagtctac cttccatacc ctgatccttc gagaatctta 17760 ggagcaggct gttttgttga tgatttactc aagactgata gcgttctctt gatagagcgt 17820 ttcgtaagtc ttgcaattga tgcttatcct ttagtatacc atgagaaccc agagtatcaa 17880 aatgtgttcc gggtatattt agaatacatc aagaagctgt acaatgatct cggtaatcag 17940 atcctggaca gctacagtgt tattttaagt acttgtgatg gtcaaaagtt tactgacgag 18000 acgttttaca agaacatgta tttaagaagt gcagtgctgc aaagcgttgg tgcctgcgtt 18060 gtctgtagtt ctcaaacatc attacgttgt ggcagttgca tacgcaagcc tttgctgtgt 18120 tgcaaatgcg cctatgatca tgttatgtcc actgatcata aatatgtcct gagtgtgtca 18180 ccatatgtgt gtaattcacc gggatgtgat gtaaatgatg ttaccaaatt gtatttaggt 18240 ggtatgtcat attattgtga ggaccataaa ccacagtatt cattcaaatt ggtgatgaat 18300 ggtatggttt ttggtttata taagcagtct tgtactggtt cgccctacat agaggatttt 18360 aataaaatcg ctagttgcaa atggacagaa gtcgatgatt atgtgctagc taatgaatgc 18420 accgaacgcc ttaaattgtt tgccgcagaa acgcagaagg ccacagaaga ggcctttaag 18480 caatgttatg cgtcagcaac gatccgtgag atcgtgagcg atcgggagtt aattttatct 18540 tgggaaattg gtaaagtccg cccgccactt aataaaaatt acgtgttcac cggctaccat 18600 tttactaata atggtaagac agttttaggt gagtatgttt ttgataagag tgagttgact 18660 aatggtgtgt attatcgcgc cacaaccact tataagttat ctgtaggtga tgtgttcatt 18720 ttaacatcac acgcagtgtc tagtttaagt gctcctacat tagtaccgca ggagaattat 18780 actagcattc gttttgctag tgtttatagt gtgcctgaga cgtttcagaa taatgtgcct 18840 aattatcagc acattggaat gaagcgctat tgtactgtac agggaccgcc tggtactggt 18900 aagtcccatc tagccattgg gctagctgtt tattattgta cagcgcgcgt ggtgtatacc 18960 gctgctagcc atgctgcagt tgacgcgctg tgtgaaaagg cacataaatt tctcaacatc 19020 aacgactgca cgcgtattgt tcctgcaaag gtgcgtgtag attgttatga taaattcaag 19080 gtcaatgaca ccactcgcaa gtatgtgttt actacaataa atgcattacc tgagttggtg 19140 actgacatta ttgtcgttga tgaagttagt atgcttacca actatgagct gtctgttatt 19200 aacagtcgtg ttagggctaa gcattatgtg tatattggcg acccggcgca gttacctgca 19260 ccacgtgtgc tactgaataa gggaactcta gaacctagat attttaattc cgttaccaag 19320 ctaatgtgtt gtttgggtcc agatattttc ttgggcacct gttatagatg ccctaaggag 19380 attgtggata cggtgtcagc cttggtttat aataataagc tgaaggctaa aaatgataat 19440 agctccatgt gctttaaggt ttattataag ggccagacta cacatgagag ttctagtgct 19500 gttaatatgc agcaaataca tttaatttcc aagtttctga aggcaaaccc cagttggagt 19560 aacgccgtat ttattagtcc ttataactcg cagaactatg ttgctaagag agtcttggga 19620 ttacaaaccc agacagtaga ctcagcgcag ggttctgaat atgattttgt tatctactca 19680 cagactgcgg aaacagcgca ttctgtcaat gtaaatagat tcaatgttgc tattacacgt 19740 gctaagaagg gtattctctg tgtcatgagt agtatgcaat tatttgagtc tcttaatttt 19800 actacactga cgttggataa gattaacaat ccacgattac agtgtactac aaatttgttt 19860 aaggattgta gcaggagcta tgtaggatat cacccagccc atgcaccatc ctttttggca 19920 gttgatgaca aatataaggt aggcggtgat ttagccgttt gccttaatgt tgctgattct 19980 gctgtcactt attcgcggct tatatcactc atgggattca agcttgactt gacccttgat 20040 ggttattgta agctgtttat aactagagat gaagctatca aacgtgttag agcctgggtt 20100 ggcttcgatg cagaaggtgc ccatgcgata cgtgatagca ttgggacaaa tttcccatta 20160 caattaggct tttcgactgg aattgatttt gttgtcgaag ccactggaat gtttgctgag 20220 agagatggtt atgtctttaa aaaggcagcc gcacgagctc ctcctggcga acaatttaaa 20280 caccttatcc cacttatgtc aagagggcag aaatgggatg tggttcgcat tagaatagta 20340 caaatgttgt cagaccacct agtggatttg gcagacagtg ttgtacttgt gacgtgggct 20400 gccagctttg agctcacatg tttgcgatat ttcgctaaag ttggaagaga agttgtgtgt 20460 agtgtctgca ccaagcgtgc gacatgtttt aattctagaa ctggatacta tggatgctgg 20520 cgacatagtt attcctgtga ttacctgtac aacccactaa tagttgacat tcaacagtgg 20580 ggatatacag gatctttaac tagcaatcat gatcctattt gcagcgtgca taagggtgct 20640 catgttgcat catctgatgc tatcatgacc cggtgtctag ctgttcatga ttgcttttgt 20700 aagtctgtta attggaattt agaatacccc attatttcaa atgaggtcag tgttaatacc 20760 tcctgcaggt tattgcagcg cgtaatgttt agggctgcga tgctatgcaa taggtatgat 20820 gtgtgttatg acattggcaa ccctaaaggt cttgcctgtg tcaaaggata tgattttaag 20880 ttctatgacg cctcccctgt tgttaagtcg gtcaaacagt ttgtttacaa atacgaggca 20940 cataaagatc aatttttaga tggtttgtgt atgttttgga actgcaatgt ggataagtat 21000 ccagcgaatg cagttgtgtg taggtttgac acgcgtgtgt tgaacaaatt aaatctccct 21060 ggctgtaatg gtggcagttt gtatgttaac aaacatgcat tccacaccag tccctttacc 21120 cgggctgcct tcgagaattt gaagcctatg cctttctttt attattcaga tacgccctgt 21180 gtgtatatgg aaggcatgga atctaagcag gtcgattatg tcccattgag aagcgctaca 21240 tgcatcacaa gatgcaattt aggtggcgct gtttgtttaa aacatgctga ggagtatcgt 21300 gagtaccttg agtcttacaa tacggcaacc acagcgggtt ttactttttg ggtctataag 21360 acttttgatt tttacaacct ttggaatact tttactaggc tccaaagttt agaaaatgta 21420 gtgtataacc tggtcaacgc tggacacttt gatggccggg cgggtgaact gccttgtgct 21480 gttataggtg agaaagtcat tgccaagatt caaaatgagg atgtcgtggt ctttaaaaat 21540 aacacgccat tccccactaa tgtggctgtc gaattatttg ctaagcgcag tattcggccc 21600 caccccgagc ttaagctctt tagaaatttg aatattgacg tgtgctggag tcacgtcctt 21660 tgggattatg ctaaggatag tgtgttttgc agttcgacgt ataaggtctg caaatacaca 21720 gatttacagt gcattgaaag cttgaatgta ctttttgatg gtcgtgataa tggtgctctt 21780 gaagctttta agaagtgccg gaatggcgtc tacattaaca cgacaaaaat taaaagtctg 21840 tcgatgatta aaggcccaca acgtgccgat ttgaatggcg tagttgtgga gaaagttgga 21900 gattctgatg tggaattttg gtttgctgtg cgtaaagacg gtgacgatgt tatcttcagc 21960 cgtacaggga gccttgaacc gagccattac cggagcccac aaggtaatcc gggtggtaat 22020 cgcgtgggtg atctcagcgg taatgaagct ctagcgcgtg gcactatctt tactcaaagc 22080 agattattat cttctttcac acctcgatca gagatggaga aagattttat ggatttagat 22140 gatgatgtgt tcattgcaaa atatagttta caggactacg cgtttgaaca cgttgtttat 22200 ggtagtttta accagaagat tattggaggt ttgcatttgc ttattggctt agcccgtagg 22260 cagcaaaaat ccaatctggt aattcaagag ttcgtgacat acgactctag cattcattcg 22320 tactttatca ctgacgagaa cagtggtagt agtaagagtg tgtgcactgt tattgattta 22380 ttgttagatg attttgtgga cattgtaaag tccctgaatc taaagtgtgt gagtaaggtt 22440 gttaatgtta atgtggattt taaggacttc cagtttatgt tgtggtgcaa tgaggagaag 22500 gtcatgactt tctatcctcg tttgcaggct gctgctgact ggaaacctgg ttatgttatg 22560 cctgtcttat ataagtattt ggaatcgcct ctggaaagag taaacctctg gaattatggc 22620 aagccgatta ctttacctac aggatgtatg atgaatgttg ctaagtatac tcaattatgt 22680 caatatttga gcactacaac attagcagtt ccggctaata tgcgtgtctt acaccttggt 22740 gccggttcgg ataagggtgt tgcccctggg tctgcagttc ttaggcagtg gctaccagcg 22800 ggaagtattc ttgtagataa tgatgtgaat ccatttgtga gtgacagtgt cgcctcatat 22860 tatggaaatt gtataacctt accctttgat tgtcagtggg atctgataat ttctgatatg 22920 tacgaccctc ttactaagaa cattggggag tacaacgtga gtaaagatgg attctttact 22980 tacctctgtc atttaattcg tgacaagttg gctctgggtg gcagtgttgc cataaaaata 23040 acagagtttt cttggaacgc tgagttatat agtttaatgg ggaagtttgc gttctggaca 23100 atcttttgca ccaacgtaaa cgcctcttca agtgaaggat ttttgattgg cataaattgg 23160 ttgaataaga cccgtaccga aattgacggt aaaaccatgc atgccaatta tctgttttgg 23220 agaaatagta caatgtggaa tggaggggct tacagtctct ttgacatgag taagttccct 23280 ttgaaagcgg ctggtacggc tgttgttagc cttaaaccag accaaataaa tgacttagtc 23340 ctctccttga ttgagaaggg caagttatta gtgcgtgata cacgcaaaga agtttttgtt 23400 ggcgatagcc tagtaaatgt caaataaacg aacaatgttt gtttttcttg ttttattgcc 23460 actagtctct agtcagtgtg ttaatcttac aaccagaact caattacccc ctgcatacac 23520 taattctttc acacgtggtg tttattaccc tgacaaagtt ttcagatcct cagttttaca 23580 ttcaactcag gacttgttct tacctttctt ttccaatgtt acttggttcc atgctataca 23640 tgtctctggg accaatggta ctaagaggtt tgataaccct gtcctaccat ttaatgatgg 23700 tgtttacttt gcttccactg agaagtctaa cataataaga ggctggattt ttggtactac 23760 tttagattcg aaaacccagt ccctacttat tgttaataac gctactaatg ttgttatcaa 23820 agtctgtgaa tttcaatttt gtaacgatcc atttttgggt gtttattacc acaaaaacaa 23880 caaaagttgg atggaaagtg agttcagagt ttattctagt gcgaataatt gcacttttga 23940 atacgtctct cagccttttc ttatggacct tgaaggaaaa cagggtaatt tcaaaaatct 24000 tagggaattt gtgttcaaga atattgatgg ttacttcaag atatactcta agcacacgcc 24060 tattaattta gtgcgtgatc tccctcaggg tttttcggct ttagaaccat tggtagattt 24120 gccaataggt attaacatca ctaggtttca aactttactt gctttacata gaagttattt 24180 aactcctggt gattcttctt caggttggac agctggtgct gcagcttatt atgtgggtta 24240 tcttcaacct aggacttttc tactgaagta caatgaaaat ggaaccatta cagatgctgt 24300 agactgtgca cttgaccctc tctcagaaac aaagtgtacg ttgaaatcct tcactgtaga 24360 aaaaggaatc tatcaaactt ctaactttag agtccaacca acagaatcta ttgttagatt 24420 tcctaacatc acaaacttgt gcccttttgg tgaagttttt aacgccacca gatttgcatc 24480 tgtttatgct tggaacagga agagaatcag caactgtgtt gctgattatt ctgtcctgta 24540 taattccgca tcattttcca cttttaagtg ttatggagtg tctcctacta aattaaatga 24600 tctctgcttt actaatgtct atgcagattc atttgtaatt agaggtgatg aagtcagaca 24660 aatcgctcca gggcaaactg gaaagattgc tgattataac tacaaattac cagatgattt 24720 tacaggctgc gttatagctt ggaattctaa caatcttgat tctaaggttg gtggtaatta 24780 taattacctg tacagattgt ttaggaagtc taatctcaaa ccttttgaga gagatatttc 24840 aactgaaatc tatcaggccg gtagcacacc ttgtaatggt gttgaaggtt ttaattgtta 24900 ctttcctctg caatcatatg gtttccaacc cactaatggt gttggttacc aaccatacag 24960 agtagtagta ctttcttttg aacttctaca tgcaccagca actgtttgtg gacctaaaaa 25020 gtctactaat ttggttaaga acaagtgtgt caatttcaac ttcaatggtt taacaggcac 25080 aggtgttctt actgagtcta acaaaaagtt tctgcctttc caacaatttg gcagagacat 25140 tgctgacact actgatgctg ttcgtgatcc acaaacactt gagattcttg acattacacc 25200 atgttctttt ggtggtgtca gtgttataac accaggaaca aatacttcta accaggttgc 25260 tgttctttat caggatgtta actgcacaga agtccctgtt gctattcatg cagatcaact 25320 tactcctact tggcgtgttt attctacagg ttctaatgtt tttcaaacac gtgcaggctg 25380 tttaataggg gctgaacatg tcaacaactc atatgagtgt gacataccca ttggtgcagg 25440 tatatgcgct agttatcaga ctcagactaa ttctcctcgg agagcaagaa gtgtagctag 25500 tcaatccatc attgcctaca ctatgtcact tggtgcagaa aattcagttg cttactctaa 25560 taactctatt gccataccca caaattttac tattagcgtt accacagaaa ttctaccagt 25620 gtctatgacc aagacatcag tagattgtac aatgtacatt tgtggtgatt caactgaatg 25680 cagcaatctt ttgttgcaat atggcagttt ttgtacacaa ttaaaccgtg ctttaactgg 25740 aatagctgtt gaacaagaca aaaacaccca agaagttttt gcacaagtca aacaaattta 25800 caagacacca ccaattaaag attttggcgg ttttaatttt agccagatac tgccagatcc 25860 atcaaaacca agcaagaggt catttattga agatctactg ttcaacaaag tgacacttgc 25920 agatgctggc ttcatcaaac aatatggtga ttgccttggt gatattgctg ctagagacct 25980 catttgtgca caaaagttta acggccttac tgttttgcca cctttgctca cagatgaaat 26040 gattgctcaa tacacttctg cactgttagc aggtacaatc acttctggtt ggacttttgg 26100 tgcaggtgct gcattacaaa taccatttgc tatgcaaatg gcttataggt ttaatggtat 26160 tggagttaca cagaatgttc tctatgagaa ccaaaaattg attgccaacc aatttaatag 26220 tgctattggc aaaattcaag actcactttc ttccacagca agtgcacttg gaaaacttca 26280 agatgtggtc aaccaaaatg cacaagcttt aaacacgctt gttaaacaac ttagctccaa 26340 ttttggtgca atttcaagtg ttttaaacga catcctttca cgtcttgaca aagttgaggc 26400 tgaagtgcaa attgataggt tgatcacagg cagacttcaa agtttgcaga catatgtgac 26460 tcaacaatta attagagctg cagaaatcag agcttctgct aatcttgctg ctactaaaat 26520 gtcagagtgt gtacttggac aatcaaaaag agttgacttt tgcggaaagg gctatcatct 26580 tatgtcattt cctcagtcag cacctcatgg tgtcgtcttt ttgcatgtga cttatgtccc 26640 tgcacaagaa aagaacttca caactgctcc tgccatttgt catgatggaa aagcacactt 26700 tcctcgtgaa ggtgtctttg tttcaaatgg cacacactgg tttgtaacac aaaggaattt 26760 ttatgaacca caaatcatta ctacagacaa cacatttgtg tctggtaact gtgatgttgt 26820 aataggaatt gtcaacaaca cagtttatga tcctttgcaa cctgaattag actcattcaa 26880 ggaggagctt gataaatact tcaagaacca tacctcacca gatgttgatt taggtgacat 26940 ctctggcatt aatgcttcag ttgtaaacat tcagaaagaa atcgaccgcc tcaatgaggt 27000 tgccaagaat ttaaatgaat ctctcatcga tctccaagaa cttggaaagt atgagcagta 27060 tataaaatgg ccatggtaca tttggctagg ttttatagct ggcttgattg ccatagtaat 27120 ggtgacaatt atgctttgct gtatgaccag ttgctgtagt tgtctcaagg gctgttgttc 27180 ttgtggatcc tgctgcaaat ttgacgagga cgactctgag ccagtgctca aaggagtcaa 27240 attacattac acataactat cacagcctct cctggaaaga cagaaaatct aaacaattta 27300 tagcattctc attgctacct ggccccgtaa gaggcagtca tagctatggc cgtgttggtc 27360 ctaaggctac attggctgct gtctttattg gtccatttat tgtagcatgt atgctaggca 27420 ttggcctagt ttatttattg caattgcaag ttcaaatttt tcatgttaag gataccatac 27480 gtgtgactgg caagccagcc actgtgtctt atactacaag tacaccagta acaccgagcg 27540 cgacgacgct cgatggtact acgtatactt taattagacc cactagctct tatacaagag 27600 tttatcttgg tactccaaga ggttttgatt atagtacatt tgggcctaag accctagatt 27660 atgttactaa tctaaacctc atcttaattc tggtcgtcca tatactttta aggcattgtc 27720 caggcatatg aggccaacag ccacatggat ttggcatgtg agtgatgcat ggttacgccg 27780 cacgcgggac tttggtgtca ttcgcctaga agatttttgt tttcaattta attatagcca 27840 accccgagtt ggttattgta gagttccttt aaaggcttgg tgtagcaacc agggtaaatt 27900 tgcagcgcag tttaccctaa aaagttgcga aaaaccaggt cacgaaaaat ttattactag 27960 cttcacggcc tacggcagaa ctgtccaaca ggccgttagc aagttagtag aagaagctgt 28020 tgattttatt ctttttaggg ccacgcagct cgaaagaaat gtttaattta ttccttacag 28080 acacagtatg gtatgtgggg cagattattt ttatattcgc agtgtgtttg atggtcacca 28140 taattgtggt tgccttcctt gcgtctatca aactttgtat tcaactttgc ggtttatgta 28200 atactttggt gctgtcccct tctatttatt tgtatgatag gagtaagcag ctttataagt 28260 actataatga agaaatgaga ctgcccctat tagaggtgga tgatatctaa tccaaacatt 28320 atgagtagta ctactcaggc cccagagccc gtctatcaat ggaccgccga cgaggcagtt 28380 caattcctta aggaatggaa cttctcgttg ggcattatac tactctttat tactatcata 28440 ctacagttcg gttacacgag ccgtagcatg tttatttatg ttgtgaaaat gataatcttg 28500 tggttaatgt ggccactgac tattgttttg tgtattttca attgcgtgta tgcgctaaat 28560 aatgtgtatc ttggattttc tatagtgttt actatagtgt ccattgtaat ctggatcatg 28620 tattttgtga acagcataag gttgtttatc aggactggta gctggtggag cttcaacccc 28680 gaaacaaaca accttatgtg tatagatatg aaaggtaccg tgtatgttag acccattatt 28740 gaggattacc atacactaac agccactatt attcgtggcc acctctacat gcaaggtgtt 28800 aagctaggca ccggtttctc tttgtctgac ttgcccgctt atgttacagt tgctaaggtg 28860 tcacaccttt gcacttataa gcgcgcattc ttagacaagg tagacggtgt tagcggtttt 28920 gctgtttatg tgaagtccaa ggtcggaaat taccgactgc cctcaaacaa accgagtggc 28980 gcggacaccg cattgttgag aacctaatct aaactttaag gagagaatga atcctatgtc 29040 ggcgctcggt ggtaacccct cgcgagaaag tcgggatagg acactctcta tcagaatgga 29100 tgtcttgctg tcataacaga tagagaaggt tgtggcagac cctgtatcaa ttagttgaaa 29160 gagattgcaa aatagagaat gtgtgagaga agttagcaag gtcctacgtc taaccataag 29220 aacggcgata ggcgccccct gggaacagct cacatcaggg tactattcct gcaatgccct 29280 agtaaatgaa tgaagttgat catggccaat tggaagaatc acaaaaaaaa aaaaaaaaaa 29340 aacggccggt ttaaacgcta cagtccaagt tccaagcggg atactagatg tataatgtcc 29400 gccatgcaga cgaaaccagt cggagattac cgagcattct atcacgtcgg cgaccaatag 29460 tgagcttagg gataacaggg taataaacga tccccgggaa ttcactggcc gtcgttttac 29520 aacgtcgtga ctgggaaaac cctggcgtta cccaacttaa tcgccttgca gcacatcccc 29580 ctttcgccag ctggcgtaat agcgaagagg cccgcaccga tcgcccttcc caacagttgc 29640 gcagcctgaa tggcgaatgg cgatagatcc ggtggatgac cttttgaatg acctttaata 29700 gattatatta ctaattaatt ggggacccta gaggtcccct tttttatttt aaaaattttt 29760 tcacaaaacg gtttacaagc ataaagctcg gacggatctt ttccgctgca taaccctgct 29820 tcggggtcat tatagcgatt ttttcggtat atccatcctt tttcgcacga tatacaggat 29880 tttgccaaag ggttcgtgta gactttcctt ggtgtatcca acggcgtcag ccgggcagga 29940 taggtgaagt aggcccaccc gcgagcgggt gttccttctt cactgtccct tattcgcacc 30000 tggcggtgct caacgggaat cctgctctgc gaggctggcc ggctaccgcc ggcgtaacag 30060 atgagggcaa gcggatggct gatgaaacca agccaaccag gaagggcagc ccacctatca 30120 aggtgtcgat gcaggggggg gggaaagcca cgttgtgtct caaaatctct gatgttacat 30180 tgcacaagat aaaaatatat catcatgaac aataaaactg tctgcttaca taaacagtaa 30240 tacaaggggt gttatgagcc atattcaacg ggaaacgtct tgctcaaggc cgcgattaaa 30300 ttccaacatg gatgctgatt tatatgggta taaatgggct cgcgataatg tcgggcaatc 30360 aggtgcgaca atctatcgat tgtatgggaa gcccgatgcg ccagagttgt ttctgaaaca 30420 tggcaaaggt agcgttgcca atgatgttac agatgagatg gtcagactaa actggctgac 30480 ggaatttatg cctcttccga ccatcaagca ttttatccgt actcctgatg atgcatggtt 30540 actcaccact gcgatccccg gaaaaacagc attccaggta ttagaagaat atcctgattc 30600 aggtgaaaat attgttgatg cgctggcagt gttcctgcgc cggttgcatt cgattcctgt 30660 ttgtaattgt ccttttaaca gcgatcgcgt atttcgtctc gctcaggcgc aatcacgaat 30720 gaataacggt ttggttgatg cgagtgattt tgatgacgag cgtaatggct ggcctgttga 30780 acaagtctgg aaagaaatgc ataagttttt gccattctca ccggattcag tcgtcactca 30840 tggtgatttc tcacttgata accttatttt tgacgagggg aaattaatag gttgtattga 30900 tgttggacga gtcggaatcg cagaccgata ccaggatctt gccatcctat ggaactgcct 30960 cggtgagttt tctccttcat tacagaaacg gctttttcaa aaatatggta ttgataatcc 31020 tgatatgaat aaattgcagt ttcatttgat gctcgatgag tttttctaat cagaattggt 31080 taattggttg taacactggc agagcattac gctgacttga cgggacggcg gctttgttga 31140 ataaatcgaa cttttgctga gttgaaggat cagatcacgc atcttcccga caacgcagac 31200 cgttccgtgg caaagcaaaa gttcaaaatc accaactggt ccacctacaa caaagctctc 31260 atcaaccgtg gctccctcac tttctggctg gatgatgggg cgattcaggc ctggtatgag 31320 tcagcaacac cttcttcacg aggcagacct cagacggtat cggatcgatc ccccgatgtg 31380 tagcagtggc ggaccatata ggcagatcag aaggcgcggt tctcctacat gagcttttca 31440 attcaattca tcattttttt tttattcttt tttttgattt cggtttcctt gaaatttttt 31500 tgattcggta atctccgaac agaaggaaga acgaaggaag gagcacagac ttagattggt 31560 atatatacgc atatgtagtg ttgaagaaac atgaaattgc ccagtattct taacccaact 31620 gcacagaaca aaaacctgca ggaaacgaag ataaatcatg tcgaaagcta catataagga 31680 acgtgctgct actcatccta gtcctgttgc tgccaagcta tttaatatca tgcacgaaaa 31740 gcaaacaaac ttgtgtgctt cattggatgt tcgtaccacc aaggaattac tggagttagt 31800 tgaagcatta ggtcccaaaa tttgtttact aaaaacacat gtggatatct tgactgattt 31860 ttccatggag ggcacagtta agccgctaaa ggcattatcc gccaagtaca attttttact 31920 cttcgaagac agaaaatttg ctgacattgg taatacagtc aaattgcagt actctgcggg 31980 tgtatacaga atagcagaat gggcagacat tacgaatgca cacggtgtgg tgggcccagg 32040 tattgttagc ggtttgaagc aggcggcaga agaagtaaca aaggaaccta gaggcctttt 32100 gatgttagca gaattgtcat gcaagggctc cctatctact ggagaatata ctaagggtac 32160 tgttgacatt gcgaagagcg acaaagattt tgttatcggc tttattgctc aaagagacat 32220 gggtggaaga gatgaaggtt acgattggtt gattatgaca cccggtgtgg gtttagatga 32280 caagggagac gcattgggtc aacagtatag aaccgtggat gatgtggtct ctacaggatc 32340 tgacattatt attgttggaa gaggactatt tgcaaaggga agggatgcta aggtagaggg 32400 tgaacgttac agaaaagcag gctgggaagc atatttgaga agatgcggcc agcaaaacta 32460 aaaaactgta ttataagtaa atgcatgtat actaaactca caaattagag cttcaattta 32520 attatatcag ttattacccg ggaatctcgg tcgtaatgat ttttataatg acgaaaaaaa 32580 aaaaattgga aagaaaaagc tgggcgcgcc ggccggccct tttcatcacg tgctataaaa 32640 ataattataa tttaaatttt ttaatataaa tatataaatt aaaaatagaa agtaaaaaaa 32700 gaaattaaag aaaaaatagt ttttgttttc cgaagatgta aaagactcta gggggatcgc 32760 caacaaatac taccttttat cttgctcttc ctgctctcag gtattaatgc cgaattgttt 32820 catcttgtct gtgtagaaga ccacacacga aaatcctgtg attttacatt ttacttatcg 32880 ttaatcgaat gtatatctat ttaatctgct tttcttgtct aataaatata tatgtaaagt 32940 acgctttttg ttgaaatttt ttaaaccttt gtttattttt ttttttcttc attccgtaac 33000 tcttctacct tctttattta ctttctaaaa tccaaataca aaacataaaa ataaataaac 33060 acagagtaaa ttcccaaatt attccatcat taaaagatac gaggcgcgtg taagttacag 33120 gcaagcgatc ggccggcccg ggcatttaaa tgcaggccgc gtacgcgtcg acggtaccga 33180 attcgcttaa acgagctcat gttcgccggt gaacgcgttg aggaagccgg gcagtgcctc 33240 ggcaaaatcc ttgcgtgtag acaagacatc tgcgtagcag ttgtcctcaa caacgatgtc 33300 gaaatccaaa tcggagtgct catcgagtcc tccgtgaacg taagagccgc cgatcagaag 33360 agcgcggaag cgaacatcgg aagcgaccgc atcgcggatg cggttcaaga aagttgcatg 33420 agcttgtgga agtgtgctga gcataaatga ttctcctagc tgttctttgg gtaagtacgc 33480 catcaggacg ttgtgagtgg cgcgattttt agcggctgaa atcagccctt gagcctgtcg 33540 gcaagtcgcg tcatgaggtc catgcgctca tgcaggatcg ccacgaccaa cgcgggttcg 33600 cccgcacgcg gcaggcaaaa aacgtagtgg tgttcgcagc gggccatccg cagcgcggga 33660 aagagttcgc tcatgtcctt aaacgggcct tcgccggcgg caagcctggc tatgccctgt 33720 tccagcttag cgatatagcg gcgcacctgc gccgcgcccc actcccggcg cgtgtagcgg 33780 atgatgccgc gtagatcggc ttcggcctca gccgtgagga tgtaggccgt caagcgcgat 33840 ccccgctgag ttcttcatca agaatttcgc cgacgctctt ggtggacacc ttgccggcaa 33900 gcccatcgtt gatgcggttc cccagcatgg ttttcagttc ctgccatgcc tgatcggcat 33960 cagcgtcacc ggggaacaga cgttcgaggg cgtattgctt aatggtcttg ccctgcaagg 34020 cggccagggc tttcaggctc tggtgctgct ggtccgtcat gtcgattgtc aggcggctca 34080 ttggataacc tccataaaat acacgtaacc acattagcac atatgtgggc gtgaggctac 34140 agcgcgaggc gcattaaggt cgggaaaatg cgctaggcgc atttaaattg cgtattgctg 34200 taatgcgcca tgccggctag actaggccca aatgggtata cccaatttga ccaaggggga 34260 cgcgatgagg gcggccaagc actaccgaca acttctatcc atcgacttca acatcgaggc 34320 gctggccttc gtgcctggac ccgacggcac acgcggccgg cgcatccacg tcctggggcg 34380 cgaggtccgc gaccggcccg gcctggtcga gtacctttcg ccggcgttcg gctcgcgggt 34440 ggcgctggac ggctactgca aggccaattt cgatgcagtg ctgcacctgg cgtaccccga 34500 tcatcagcaa tggggccacg catgaagcgc cgaagctacg ccatgctgcg cgccgctgcc 34560 gcgctggccg tcctggtcgt tgcctcgccg gcatgggccg agctgcgcgg cgaggtcgtg 34620 cgcatcatcg acggcgacac catcgacgtg ctggtagaca agcagccggt gcgcgtgcgc 34680 ctggtggaca ttgacgcgcc ggaaaagcgg caagccttcg gcgaacgtgc gcgccaggcg 34740 ctggccggca tggtgttccg ccggcacgtc ctggtcgacg agaaggacac cgaccgttac 34800 ggccgcacgc tgggcaccgt gtgggtcaac atggagctgg ccagccggcc gccgcagccg 34860 cgcaacgtca acgccgcgat ggttcaccag ggcatggcgt gggcctatcg cttccacggc 34920 cgcgcggccg accctgaaat gctgcggctc gaacaggagg cgcgaggcaa gcgcgtcggc 34980 ctctggtccg atccgcacgc cgtcgagccg tggaaatggc gacgcgagag caacaaccgg 35040 agggacgaag gttgaaggtc gcccgcatct acctgcgcgc cagtacggac gagcagaatc 35100 ttgaacgcca ggagagcctt gtagcggcca cgcgggccgc cgggtactac gtcgccggca 35160 tctaccgcga gaaggcgtcc ggcgcacgcg ccgaccggcc cgagctgctg cgcatgatcg 35220 cggacctgca acctggtgaa gtcgtcgttg cggagaagat cgaccgcatc agccgcttgc 35280 cgttggccga ggccgagcgc ctggttgcgt cgatccgggc caaaggggcc aagctggccg 35340 tgcctggcgt ggtggacctg tcggagctgg ccgccgaggc gaacggagtg gcgaaaatcg 35400 ttctggaatc cgtccaggac atgcttttga agctcgcctt gcagatggcc cgcgacgact 35460 acgaggatcg gcgcgagcgt caacgtcagg gtgtccagtt ggcgaaggcc gccggccgct 35520 acaccggccg caaacgtgac gccggcatgc acgaccgcat catcacgctt cgctccggcg 35580 gatcgagcat tgccaagacg gccaagctgg tcggatgcag cccgagccag gtcaaacgag 35640 tgtgggcggc ctggaacgcg cagcagcaaa aataaagccg ggcagtgccc ggcttttctc 35700 accttttcgc gtcccgcagg gccgctgcga gcgccctacc tagatcctcg ctttccccct 35760 cggtgtagtc cggccagggc acgaagggcg cggatgcgaa cctgttgagc aggtacgcct 35820 tcgggcagcg gtagaccacc ggcgagttcg ccttttcatc ccaccgggcc aggatcacgt 35880 ccgcatcgca gtgcatgtcc ttcacctggt cgcggaagaa gccgaaggcc accatgccgc 35940 tatgttcgcc gaggaacgcc agttgcttcg cgctggcgat cgcgccgacg ccgccggcca 36000 aaaccgacgc catcacccag ccgacgaacc agaagctggc atgcttgcgg ttgaccaccg 36060 cacgcgcagc cgcgaccagg acaacggcca agctgccgac cagggccatg acgaccgtga 36120 tccggccgtt gtggaaagcg atgggcttgc cagcgtccgc ttgcacggcg tcgtaaatgc 36180 tggacccgat gggcgcgcac atcagcacga caggcagcag caccaggaac atcgtccgcg 36240 tccattgcgc gagtgccttg cggcgttcgc cggcggcaag cgcctccatc atcggcgtga 36300 agcccaacag ggccaccgca gccgccaagc cggcaacgat gccgcaggcg attacataca 36360 tacatcctcc ctaatgcgcc ttgcgcacgg ttgtagtcag agtccgcggt ggggcgataa 36420 gctcatgacc aaaatccctt aacgtgagtt ttcgttccac tgagcgtcag accccgtaga 36480 aaagatcaaa ggatcttctt gagatccttt ttttctgcgg gggatcagga ccgctgccgg 36540 agcgcaaccc actcactaca gcagagccat gtagacaaca tcccctcccc ctttccaccg 36600 cgtcagacgc ccgtagcagc ccgctacggg ctttttcatg ccctgcccta gcgtccaagc 36660 ctcacggccg cgctcggcct ctctggcggc cttctggcgc tcctgctgcg gcgtccgctc 36720 gtgggccgtg gcgcgggtcc gcgcgccggc ctcgtgcgcc tggcgctcgc gggcgaggtc 36780 cagggcggcc gtcttcacgt tctgccttgc gcagatgaga tagatcgatc tagcgtggac 36840 tcaaggctct cgcgaatggc tcgcgttgga aactttcatt gacacttgag gggcaccgca 36900 gggaaattct cgtccttgcg agaaccggct atgtcgtgct gcgcatcgag cctgcgccct 36960 tggcttgtct cgcccctctc cgcgtcgcta cggggcttcc agcgcctttc cgacgctcac 37020 cgggctggtt gccctcgccg ctgggctggc ggccgtctat ggccctgcaa acgcgccaga 37080 aacgccgtcg aagccgtgtg cgagacaccg cggccgccgg cgttgtggat acctcgcgga 37140 aaacttggcc ctcactgaca gatgaggggc ggacgttgac acttgagggg ccgactcacc 37200 cggcgcggcg ttgacagatg aggggcaggc tcgatttcgg ccggcgacgt ggagctggcc 37260 agcctcgcaa atcggcgaaa acgcctgatt ttacgcgagt ttcccacaga tgatgtggac 37320 aagcctgggg ataagtgccc tgcggtattg acacttgagg ggcgcgacta ctgacagatg 37380 aggggcgcga tccttgacac ttgaggggca gagtgctgac agatgagggg cgcacctatt 37440 gacatttgag gggctgtcca caggcagaaa atccagcatt tgcaagggtt tccgcccgtt 37500 tttcggccac cgctaacctg tcttttaacc tgcttttaaa ccaatattta taaaccttgt 37560 ttttaaccag ggctgcgccc tgtgcgcgtg accgcgcacg ccgaaggggg gtgccccccc 37620 ttctcgaacc ctcccggccc gctaacgcgg gcctcccatc cccccagggg ctgcgcccct 37680 cggccgcgaa cggcctcacc ccaaaaatgg cagcgctggc agtccttgcc attgccggga 37740 tcggggcagt aacgggatgg gcgatcagcc cgagcgcgac gcccggaagc attgacgtgc 37800 cgcaggtgct ggcatcgaca ttcagcgacc aggtgccggg cagtgagggc ggcggcctgg 37860 gtggcggcct gcccttcact tcggccgtcg gggcattcac ggacttcatg gcggggccgg 37920 caatttttac cttgggcatt cttggcatag tggtcgcggg tgccgtgctc gtgttcgggg 37980 gtgaattaat tccccggatc gatccgtcag cttcacgctg ccgcaagcac tcagggcgca 38040 agggctgcta aaggaagcgg aacacgtaga aagccagtcc gcagaaacgg tgctgacccc 38100 ggatgaatgt cagctactgg gctatctgga caagggaaaa cgcaagcgca aagagaaagc 38160 aggtagcttg cagtgggctt acatggcgat agctagactg ggcggtttta tggacagcaa 38220 gcgaaccgga attgccagct ggggcgccct ctggtaaggt tgggaagccc tgcaaagtaa 38280 actggatggc tttcttgccg ccaaggatct gatggcgcag gggatcaaga tcgacggatc 38340 gatccgggga attaattccg gggcaatccc gcaaggaggg tga 38383 <210> 41 <211> 29494 <212> DNA <213> Artificial Sequence <220> <223> Synthesis optimized sequence E-protein and ORF6 double deletion <400> 41 caaatataac gaaaggctca gtcgaaagac tgggcctttc gttttatctg ttgtttgtcg 60 taatacgact cactataggg attaaaggtt tataccttcc caggtaacaa accaaccaac 120 tttcgatctc ttgtagatct gttctctaaa cgaactttaa aatctgtgtg gctgtcactc 180 ggctgcatgc ttagtgcact cacgcagtat aattaataac taattactgt cgttgacagg 240 acacgagtaa ctcgtctatc ttctgcaggc tgcttacggt ttcgtccgtg ttgcagccga 300 tcatcagcac atctaggttt cgtccgggtg tgaccgaaag gtaagatgga gagccttgtc 360 cctggtttca acgagaaaac acacgtccaa ctcagtttgc ctgttttaca ggttcgcgac 420 gtgttagtac gtggttttgg agattcagtg gaagaagtct tatcagaggc acgtcaacat 480 cttaaagatg gcacttgtgg cttagtagaa gttgaaaaag gcgttttgcc tcaacttgaa 540 cagccctatg tgttcatcaa acgttctgat gctagaactg cacctcatgg tcatgttatg 600 gttgagctgg tagcagaatt agaaggtatt cagtacggtc gtagtggtga gacattaggt 660 gttttagttc ctcatgtggg cgaaatacca gtggcttacc gcaaagttct tcttagaaag 720 aacggtaata aaggagctgg tggccatagt tacggcgctg atttaaagtc atttgactta 780 ggcgacgagc ttggcactga tccttatgaa gatttccaag aaaactggaa cactaaacat 840 agcagtggtg ttacccgtga actcatgcgt gagttaaatg gaggtgcata cactcgctat 900 gtcgataaca acttctgtgg acctgatggt taccctcttg agtgcattaa agaccttcta 960 gcacgtgctg gtaaagcttc atgcactttg tccgaacaac tggactttat tgacactaag 1020 aggggtgtat actgctgccg tgaacatgag catgaaattg cttggtacac ggaacgttct 1080 gaaaagagct atgaattgca gacacctttt gaaattaaac tggcaaagaa atttgacacc 1140 ttcaatgggg aatgtccaaa ttttgtattt cccctcaatt ccataatcaa gactattcaa 1200 ccaagggttg aaaagaaaaa gcttgatggc tttatgggta gaattcgatc tgtctatcca 1260 gttgcgtcac caaatgaatg caaccaaatg tgcctttcaa ctctcatgaa gtgtgatcat 1320 tgtggtgaaa cttcatggca gacgggcgat tttgttaaag ccacttgcga attttgtggc 1380 actgagaatt tgactaaaga aggtgccact acttgtggtt acttacccca aaatgctgtt 1440 gttaaaattt actgtccagc atgtcacaat tcagaagtag gacctgagca tagtcttgcc 1500 gaataccata atgaatctgg cttgaaaacc attcttcgta agggtggtcg cactattgct 1560 tttggaggat gtgtgttctc ttatgttggt tgccataaca agtgtgctta ttgggttcca 1620 cgtgcttcag ctaacatagg ttgtaaccat acaggtgttg ttggagaagg ttccgaaggt 1680 cttaatgaca accttcttga aatactccaa aaagagaaag tcaacatcaa tattgttggt 1740 gactttaaac ttaatgaaga gatcgccatt attttggcat ctttttctgc ttccacaagt 1800 gcttttgtgg aaactgtgaa aggtttggat tataaagcat tcaaacagat tgttgaatcc 1860 tgtggtaatt ttaaggttac aaagggaaaa gctaaaaaag gtgcctggaa tattggtgaa 1920 cagaaatcaa tactgagtcc tctttatgca tttgcatcag aggctgctcg tgttgtacga 1980 tcaattttct cccgcactct tgaaactgct caaaattctg tgcgtgtttt acagaaggcc 2040 gctataacaa tactagatgg aatttcacag tattcactga gactcattga tgctatgatg 2100 ttcacatctg atttggctac taacaatcta gttgtaatgg cctacattac aggtggtgtt 2160 gttcagttga cttcgcagtg gctaactaac atctttggca ctgtttatga aaaactcaaa 2220 cccgtccttg attggcttga agagaagttt aaggaaggtg tagagtttct tagagacggt 2280 tgggagattg ttaaattcat ctcaacctgt gcttgtgaaa ttgtcggtgg acaaattgtc 2340 acctgtgcta aggaaattaa ggagagtgtt cagacattct ttaagcttgt aaacaagttt 2400 ttggctttgt gtgctgactc tatcattatt ggtggagcta aacttaaagc cttgaattta 2460 ggtgaaacat ttgtcacgca ctcaaaggga ttgtacagaa agtgtgttaa atccagagaa 2520 gaaactggcc tactcatgcc tctaaaagcc ccaaaagaaa ttatcttctt agagggagaa 2580 acacttccca cagaagtgtt aacagaggaa gttgtcttga aaactggtga tttacaacca 2640 ttagaacaac ctactagtga agctgttgaa gctccattgg ttggtacacc agtttgtatt 2700 aacgggctta tgttgctcga aatcaaagac acagaaaagt actgtgccct tgcacctaat 2760 atgatggtaa caaacaatac cttcacactc aaaggcggtg caccaacaaa ggttactttt 2820 ggtgatgaca ctgtgataga agtgcaaggt tacaagagtg tgaatatcac ttttgaactt 2880 gatgaaagga ttgataaagt acttaatgag aagtgctctg cctatacagt tgaactcggt 2940 acagaagtaa atgagttcgc ctgtgttgtg gcagatgctg tcataaaaac tttgcaacca 3000 gtatctgaat tacttacacc actgggcatt gatttagatg agtggagtat ggctacatac 3060 tacttatttg atgagtctgg tgagtttaaa ttggcttcac atatgtattg ttctttctac 3120 cctccagatg aggatgaaga agaaggtgat tgtgaagaag aagagtttga gccatcaact 3180 caatatgagt atggtactga agatgattac caaggtaaac ctttggaatt tggtgccact 3240 tctgctgctt tacaacctga agaagaacaa gaagaagatt ggttagatga tgatagtcaa 3300 caaactgttg gtcaacaaga cggcagtgag gacaatcaga caactactat tcaaacaatt 3360 gttgaggttc aacctcaatt agagatggaa cttacaccag ttgttcagac tattgaagtg 3420 aatagtttta gtggttatct taaacttact gacaatgtat acatcaagaa tgcagacatt 3480 gtggaagaag ctaaaaaggt aaaaccaaca gtggttgtta atgcagccaa tgtttacctt 3540 aaacatggag gaggtgttgc aggagcctta aataaggcta ctaacaatgc catgcaagtt 3600 gaatctgatg attacatagc tactaatgga ccacttaaag tgggtggtag ttgtgtttta 3660 agcggacaca atcttgctaa acactgttta catgttgtcg gcccaaatgt taacaaaggt 3720 gaagatattc aacttcttaa gagtgcttat gaaaatttta accagcacga agttctactt 3780 gcaccattat tatcagctgg tatttttggt gctgacccta tacattcttt aagagtttgt 3840 gtagatactg ttcgcacaaa tgtctactta gctgtctttg ataaaaatct ctatgacaaa 3900 cttgtttcaa gctttttgga aatgaagagt gaaaagcaag ttgaacaaaa gatcgctgag 3960 attcctaaag aggaagttaa gccatttata actgaaagta aaccttcagt tgaacagaga 4020 aaacaagatg ataagaagat caaagcttgt gttgaagaag ttacaacaac tctggaagaa 4080 actaagttcc tcacagaaaa cttgctcctt tatatcgaca ttaatggcaa tcttcatcca 4140 gattctgcca ctcttgttag tgacattgac atcactttct taaagaaaga tgctccatat 4200 atagtgggtg atgttgttca agagggtgtt ttaactgctg tggttatacc tactaaaaag 4260 gctggtggca ctactgaaat gctagcgaaa gctttgagaa aagtgccaac agacaattat 4320 ataaccactt acccgggtca gggtttaaat ggttacactg tagaggaggc aaagacagtg 4380 cttaaaaagt gtaaaagtgc cttttacatt ctaccatcta ttatctctaa tgagaagcaa 4440 gaaattcttg gaactgtttc ttggaatttg cgagaaatgc ttgcacatgc agaagaaaca 4500 cgcaaattaa tgcctgtctg tgtggaaact aaagccatag tttcaactat acagcgtaaa 4560 tataagggta tcaagataca agagggtgtg gttgattatg gtgctagatt ttacttttac 4620 accagtaaaa caactgtagc gtcacttatc aacacactta acgatctaaa tgaaactctt 4680 gttacaatgc cacttggcta tgtaacacat ggcttaaatt tggaagaagc tgctcggtat 4740 atgagatctc tcaaagtgcc agctacagtt tctgtttctt cacctgatgc tgttacagcg 4800 tataatggtt atcttacttc ttcttctaaa acacctgaag aacattttat tgaaaccatc 4860 tcacttgctg gttcctataa agattggtcc tattctggac aatctacaca actaggtata 4920 gaatttctta agagaggtga taaaagtgta tattacacgt ccaatcctac cacattccac 4980 ctagatggtg aagttatcac ctttgacaat cttaagacac ttctttcttt gagagaagtg 5040 aggactatta aggtgtttac aacagtagac aacattaacc tccacacgca agttgtggac 5100 atgtcaatga catatggaca acagtttggt ccaacttatt tggatggagc tgatgttact 5160 aagataaaac ctcataactc acatgaaggt aaaacatttt acgttttgcc taatgatgac 5220 actctacgtg ttgaggcttt tgagtactac cacacaactg atcctagttt tctgggtagg 5280 tacatgtcag cattaaatca cactaaaaag tggaaatacc cacaagttaa tggtttaact 5340 tcgattaaat gggcagataa caactgttat cttgccactg cattgttaac actccaacaa 5400 atagagttga agtttaatcc acctgctcta caagatgctt attacagagc aagggctggt 5460 gaagctgcta acttttgtgc acttatctta gcctactgta ataagacagt aggtgagtta 5520 ggtgatgtta gagaaacaat gagttacttg tttcaacatg ccaatttaga ttcttgcaaa 5580 agagtcttga acgtggtgtg taaaacttgt ggacaacagc agacaaccct taagggtgta 5640 gaagctgtta tgtacatggg cacactttct tatgaacaat tcaagaaagg tgttcagata 5700 ccttgtacgt gtggtaaaca agctacaaaa tatctagtac aacaggagtc accttttgtt 5760 atgatgtcag caccacctgc tcagtatgaa cttaagcatg gtacatttac ttgtgctagt 5820 gagtacactg gtaattacca gtgtggtcac tataagcata taacttctaa ggaaactttg 5880 tattgcatag acggtgcttt acttacaaag tcctcagaat acaaaggtcc tattacggat 5940 gttttctaca aagaaaacag ttacacaaca accataaaac cagttactta taagttggat 6000 ggtgttgttt gtacagaaat tgaccctaag ttggacaatt attataagaa ggacaactct 6060 tatttcacag agcaaccaat tgatcttgta ccaaaccaac catatccaaa cgcaagcttc 6120 gataatttta agttcgtatg cgataatatc aaatttgctg atgatctcaa ccagttaact 6180 ggttataaga aacctgcttc aagagagctt aaagttacat ttttccctga cttaaatggt 6240 gatgtggtgg ctattgatta taaacactac acaccctctt ttaagaaagg agctaaattg 6300 ttacataagc ctattgtttg gcatgttaac aatgcaacta ataaagccac gtataaacca 6360 aatacctggt gtatacgttg tctttggagc acaaaaccag ttgaaacatc aaattcgttt 6420 gatgtactga agtcagagga cgcgcaggga atggataatc ttgcatgtga agatctaaaa 6480 ccagtctctg aagaagtagt ggaaaatcct accatacaga aagacgttct tgagtgtaat 6540 gtgaaaacta ccgaagttgt aggagacatt atacttaaac cagcaaataa tagtttgaag 6600 atcacagaag aggttggcca cacagatcta atggctgctt atgtagacaa ttctagtctt 6660 actattaaga aacctaatga actctctaga gtattaggtt tgaaaaccct tgctactcat 6720 ggtttagctg ctgttaatag tgtcccttgg gatactatag ctaattatgc taagcctttt 6780 cttaacaaag ttgttagtac aactactaac atagttacac ggtgtcttaa tcgtgtttgt 6840 actaattata tgccttactt ctttacttta ttgctacaat tgtgtacttt tactagaagt 6900 acaaattcta gaatcaaggc atctatgccg actactatag caaagaatac tgttaagagt 6960 gtcggtaaat tttgtctaga ggcttcattt aattatctca agtcacctaa cttttctaag 7020 ctgataaaca ttatcatctg gtttttgcta ttaagtgttt gcctaggttc tttaatctac 7080 tcaaccgctg ctttaggtgt tttaatgtct aatttaggca tgccttctta ctgtactggt 7140 tacagagaag gctatttgaa ctctactaat gtcactattg caacctactg tactggatct 7200 ataccttgta gtgtttgtct tagtggttta gattctttag acacctatcc ttctcttgaa 7260 actatacaga ttaccatttc atctttcaaa tgggatttaa ctgcttttgg cttagttgca 7320 gagtggtttt tggcatatat tcttttcact aggtttttct atgtacttgg attggctgca 7380 atcatgcaat tgtttttcag ctattttgca gtccatttta ttagtaactc ttggcttatg 7440 tggcttataa ttaatcttgt gcagatggcc ccgatttcag ctatggttag aatgtacatc 7500 ttctttgcct cattttatta tgtgtggaaa agttatgtgc atgttgtaga cggttgtaat 7560 tcatcaactt gtatgatgtg ttacaaacgt aatagagcaa caagagtcga atgtacaact 7620 attgttaatg gtgttagaag gtccttttat gtctatgcta atggaggtaa aggcttttgc 7680 aaactacaca attggaattg tgttaattgt gatacattct gtgctggtag tacatttatt 7740 agtgatgaag ttgcgagaga cttgtcacta cagtttaaaa gaccaataaa tcctactgac 7800 caatcttctt acatcgttga tagtgttaca gtgaagaatg gttccatcca tctttacttt 7860 gataaagctg gtcaaaagac ttatgaaaga cattctctct ctcattttgt taacttagac 7920 aacctgagag ctaataacac taaaggttca ttgcctatta atgttatcgt tttcgacggt 7980 aaatcaaaat gtgaagaatc atctgcaaaa tcagcgtctg tttactacag tcagcttatg 8040 tgtcaaccta tactgttact agatcaggca ttagtgtctg atgttggtga tagtgcggaa 8100 gttgcagtta aaatgtttga tgcttacgtt aatacgtttt catcaacttt taacgtacca 8160 atggaaaaac tcaaaacact agttgcaact gcagaagctg aacttgcaaa gaatgtgtcc 8220 ttagacaatg tcttatctac gtttatttca gcagctcggc aagggtttgt tgattcagat 8280 gtagaaacta aagatgttgt tgaatgtctt aaattgtcac atcaatctga catagaagtt 8340 actggcgata gttgtaataa ctatatgctc acctataaca aagttgaaaa catgacaccc 8400 cgtgaccttg gtgcttgtat tgactgtagt gctagacata ttaatgcgca ggtagcaaaa 8460 agtcacaaca ttgctttgat atggaacgtt aaagatttca tgtcattgtc tgaacaacta 8520 cgaaaacaaa tacgtagtgc tgctaaaaag aataacttac ccttcaagtt gacatgtgca 8580 actactagac aagttgttaa tgttgtaaca acaaagatag cacttaaggg tggtaaaatt 8640 gtgaataact ggttgaagca gcttattaaa gttacacttg tgttcctttt tgttgctgct 8700 attttctatc tgataacacc tgttcatgtc atgtctaaac atactgactt ttcaagtgaa 8760 atcataggat acaaggctat tgatggtggt gtcactcgtg acatagcatc tacagatact 8820 tgttttgcta acaaacatgc tgattttgac acatggttta gccagcgtgg tggtagttat 8880 actaatgaca aagcttgccc attgattgct gcagtcataa caagagaagt gggttttgtc 8940 gttcctggtt tgcctggaac gatattacgc acaactaatg gtgacttttt gcatttctta 9000 cctagagttt ttagtgcagt tggtaacatc tgttacacac catcaaaact tatagagtac 9060 actgactttg caacatcagc ttgtgttttg gctgctgaat gtacaatttt taaagacgct 9120 tctggtaagc cagtaccata ttgttatgat accaatgtac tagaaggttc tgttgcttat 9180 gaaagtttac gccctgacac acgttatgtg ctcatggatg gctctattat tcaatttcct 9240 aacacctacc ttgaaggttc tgtaagagtg gtaacaactt ttgattctga gtactgtagg 9300 cacggcactt gtgaaagatc agaagctggt gtttgtgtat ctactagtgg tagatgggta 9360 cttaacaacg attattacag atctttacca ggagttttct gtggtgtaga tgctgtaaat 9420 ttgcttacta acatgtttac accactaatt caacctattg gtgctttgga catatcagca 9480 tctatagtag ctggtggtat tgtagctatc gtagtaacat gccttgccta ctattttatg 9540 aggtttagac gtgcttttgg tgaatacagt catgtagttg cctttaatac tctcctattc 9600 cttatgtcat tcactgtact ctgtttaaca ccagtttact cattcttacc tggtgtttat 9660 tctgttattt acctgtactt gacattttat ctgactaatg atgtttcttt tctcgcacat 9720 attcagtgga tggttatgtt cacaccttta gtacctttct ggataacaat tgcttacatc 9780 atttgtattt ccacaaagca tttctattgg ttctttagta attacctaaa gagacgtgta 9840 gtctttaatg gtgtttcctt tagtactttt gaagaagctg cgctgtgcac ctttttgtta 9900 aataaggaga tgtatctaaa gttgcgtagt gatgtgctat tacctcttac gcaatataat 9960 agatacttag ctctttataa caagtacaag tatttcagtg gagcaatgga tacaactagc 10020 tacagagaag ctgcttgttg tcatctcgca aaggctctca atgacttcag taactcaggt 10080 tctgatgttc tttaccaacc accacaaacc tctatcacct cagctgtttt gcagagtggt 10140 tttagaaaaa tggcattccc atctggtaaa gttgagggtt gtatggtaca agtaacttgt 10200 ggtacaacta cacttaacgg tctttggctt gatgacgtag tttactgtcc aagacatgtg 10260 atctgcacct ctgaagatat gcttaaccct aattatgaag atctactcat ccgtaagtct 10320 aatcataact tcttggtaca ggctggtaat gttcaactca gggttattgg acattctatg 10380 caaaattgtg tacttaagct taaggttgat acagccaatc ctaagacacc taagtataag 10440 tttgttcgca ttcaaccagg acagactttt tcagtgttag cttgttacaa tggttcacca 10500 tctggtgttt accaatgtgc tatgaggccc aatttcacta ttaagggttc attccttaat 10560 ggttcatgtg gtagtgttgg ttttaacata gattatgact gtgtctcttt ttgttacatg 10620 caccatatgg aattaccaac tggagttcat gctggcacag acttagaagg taacttttat 10680 ggaccttttg ttgacaggca aacagcacaa gcagctggta cagatacaac tattacagtt 10740 aatgttcttg cttggttgta cgctgctgtt ataaatggag acaggtggtt tctcaatcga 10800 tttaccacaa ctcttaatga ctttaacctt gtggctatga agtacaatta tgaacctcta 10860 acacaagacc atgttgacat actaggacct ctttctgctc aaactggaat tgccgtttta 10920 gatatgtgtg cttcattaaa agaacttctg caaaatggta tgaatggacg taccatattg 10980 ggtagtgctt tattagaaga tgagtttaca ccttttgatg ttgttagaca atgctcaggt 11040 gttactttcc aaagtgcagt gaaaagaaca atcaagggta cacaccactg gttgttactc 11100 acaattttga cttcactttt agttttagtc cagagtactc aatggtcttt gttctttttc 11160 ttctacgaaa atgccttttt accttttgct atgggtatta ttgctatgtc tgcttttgca 11220 atgatgtttg tcaaacataa gcatgcattt ctctgtttgt ttttgttacc ttctcttgcc 11280 actgtagctt actttaatat ggtctacatg cctgctagtt gggtgatgcg tattatgaca 11340 tggttggata tggttgatac tagtttgtct ggttttaagc taaaagactg tgttatgtat 11400 gcatcagctg tagtgttact aatccttatg acagcaagaa ctgtgtatga tgatggtgct 11460 aggagagtgt ggacacttat gaatgtcttg acactcgttt ataaagttta ctatggcaac 11520 gctttagatc aagccatttc catgtgggct cttataatct ctgttacttc taactactca 11580 ggtgtagtta caactgtcat gtttttggcc agaggtattg tttttatgtg tgttgagtat 11640 tgccctattt tcttcataac tggtaataca cttcagtgta taatgctagt ctattgtttc 11700 ttaggctatt tttgtacttg ttacttcggc ctcttttgtt tactcaaccg ctactttaga 11760 ctgactcttg gtgtttatga ttacttagtg tctacacagg agtttagata tatgaattca 11820 cagggactac tcccacccaa gaatagcata gatgccttca aactcaacat taaattgttg 11880 ggtgttggtg gcaaaccttg tatcaaagta gccactgtac agtctaaaat gtcagatgta 11940 aagtgcacat cagtagtctt actctcagtt ttgcaacaac tcagagtaga atcatcatct 12000 aaattgtggg ctcaatgtgt ccagttacac aatgacattc tcttagctaa agatactact 12060 gaagcctttg aaaaaatggt ttcactactt tctgttttgc tttccatgca gggtgctgta 12120 gacataaaca agctttgtga agaaatgctg gacaacaggg caaccttaca agctatagcc 12180 tcagagttta gttcccttcc atcatatgca gcttttgcta ctgctcaaga agcttatgag 12240 caggctgttg ctaatggtga ttctgaagtt gttcttaaaa agttgaagaa gtctttgaat 12300 gtggctaaat ctgaatttga ccgtgatgca gccatgcaac gtaagttgga aaagatggct 12360 gatcaagcta tgacccaaat gtataaacag gctagatctg aggacaagag ggcaaaagtt 12420 actagtgcta tgcagacaat gcttttcact atgcttagaa agttggataa tgatgcactc 12480 aacaacatta tcaacaatgc aagagatggt tgtgttccct tgaacataat acctcttaca 12540 acagcagcca aactaatggt tgtcatacca gactacaaca catataagaa tacgtgtgat 12600 ggtacaacat ttacttatgc atcagcattg tgggaaatcc aacaggttgt agatgcagat 12660 agtaaaattg ttcagcttag tgaaattagt atggacaatt cacctaattt agcatggcct 12720 cttattgtaa cagctttaag ggccaattct gctgtcaaat tacagaataa tgagcttagt 12780 cctgttgcac taagacaaat gtcttgtgct gccggtacta cacaaactgc ttgcactgat 12840 gacaatgcgt tagcttacta caacacaaca aagggaggta ggtttgtact tgcactgtta 12900 tccgatttac aggatttgaa atgggctaga ttccctaaga gtgatggaac tggtactatc 12960 tatacagaac tggaaccacc ttgtaggttt gttacagaca cacctaaagg tcctaaagtg 13020 aagtatcttt acttcatcaa aggattaaac aacctaaata gaggtatggt acttggtagt 13080 ttagctgcca cagtacgttt acaagctggt aatgcaacag aagttcctgc taattcaact 13140 gtactttctt tctgtgcttt tgctgtagat gctgctaaag cttacaaaga ttatctagct 13200 agtgggggac aaccaatcac taattgtgtt aagatgttgt gtacacacac tggtactggt 13260 caggcaataa cagttacacc ggaagccaat atggatcaag aatcctttgg tggtgcatcg 13320 tgttgtctgt actgccgttg tcatatagat catccaaatc ctaaaggatt ttgtgactta 13380 aaaggtaagt atgtacaaat acctacaact tgtgctaatg accctgtggg ttttacactt 13440 aaaaacacag tctgtaccgt ctgcggtatg tggaaaggtt atggttgtag ttgtgatcaa 13500 ctccgcgaac ccatgcttca gtcagctgat gcacaatcgt ttttaaacgg gtttgcggtg 13560 taagtgcagc ccgtcttaca ccgtgcggca caggcactag tactgatgtc gtatatagag 13620 cttttgacat ctacaatgat aaagtagctg gttttgctaa gttcctaaaa actaattgtt 13680 gtcgcttcca agaaaaggac gaagatgaca atctcattga ttcttacttt gtagttaaga 13740 gacacacttt ctctaactac caacatgaag aaacaattta caacctgctt aaggattgtc 13800 cagctgttgc taaacatgac ttctttaagt ttagaataga cggtgacatg gtaccacata 13860 tatcacgtca acgtcttact aaatacacaa tggcagacct cgtctatgct ttaaggcatt 13920 ttgatgaagg taattgtgac acattaaaag aaatacttgt cacatacaat tgttgtgatg 13980 atgactactt caataaaaag gactggtatg attttgtaga aaacccagat atattacgcg 14040 tatacgccaa cttaggtgaa cgtgtacgcc aagctttgtt aaaaacagta cagttctgtg 14100 atgccatgcg aaatgctggt attgttggtg tactgacatt agataatcaa gatctcaatg 14160 gtaactggta tgactttggt gatttcatac aaaccacgcc aggtagtgga gttcctgttg 14220 tagactctta ttattcattg ctcatgccta tattaacctt gaccagggct ttaactgcag 14280 agtcacatgt tgacactgac ttaacaaagc cttacattaa gtgggatttg ttaaaatacg 14340 acttcacgga agagaggtta aaactctttg accgttattt taaatactgg gatcagacat 14400 accacccaaa ttgtgttaac tgtttggatg acagatgcat tctgcattgt gcaaacttta 14460 atgttctgtt ctctacagtg ttcccaccta caagttttgg accactagtg agaaaaatat 14520 ttgttgatgg tgttccattt gtagtttcaa ctggatacca cttcagagag ctaggtgttg 14580 tacataatca ggatgtaaac ttacatagct ctagacttag ttttaaggaa ttacttgtgt 14640 atgctgctga tcctgctatg catgctgctt ctggtaatct attactagat aaacgcacta 14700 cgtgcttttc agtagctgca cttactaaca atgttgcttt tcaaactgtc aaacccggta 14760 attttaacaa ggacttctat gactttgctg tgtctaaggg tttctttaag gaaggaagtt 14820 ctgttgaatt aaaacacttc ttctttgctc aggatggtaa tgctgctatc agcgattatg 14880 actactatcg ttataatcta ccaacaatgt gtgatatcag acaactacta tttgtagttg 14940 aagttgttga taagtacttt gattgttacg atggtggctg tattaatgct aaccaagtca 15000 tcgtcaacaa cctagacaaa tcagctggtt ttccatttaa taaatggggt aaggctagac 15060 tttattatga ttccatgagt tatgaggatc aagatgcact tttcgcatat acaaaacgta 15120 atgtcatccc tactataact caaatgaacc ttaagtatgc cattagtgca aagaatagag 15180 ctcgcaccgt agctggtgtc tctatctgta gtactatgac caatagacag tttcatcaaa 15240 aattactcaa gtcaatagcc gccactagag gagctactgt agtaattgga acaagcaaat 15300 tctatggtgg ttggcacaac atgctcaaaa ctgtttatag tgatgtagaa aaccctcacc 15360 ttatgggttg ggattatcct aaatgtgata gagccatgcc taacatgctt agaattatgg 15420 cctcacttgt tcttgctcgc aaacatacaa cgtgttgtag cttgtcacac cgtttctata 15480 gattagctaa tgagtgtgct caagtattga gtgaaatggt catgtgtggc ggttcactat 15540 atgttaaacc aggtggaacc tcatcaggag atgccacaac tgcttatgct aatagtgtgt 15600 ttaacatttg tcaagctgtc acggccaatg ttaatgcact tttatctact gatggtaaca 15660 aaattgccga taagtatgtc cgcaatttac aacacagact ttatgagtgt ctctatagaa 15720 atagagatgt tgacacagac tttgtgaatg agttttacgc atatttgcgt aaacatttct 15780 caatgatgat actctctgac gatgctgttg tgtgtttcaa tagcacttat gcatctcaag 15840 gtctagtggc tagcataaag aactttaagt cagttcttta ctatcaaaac aacgttttta 15900 tgtctgaagc aaaatgttgg actgagactg accttactaa aggacctcat gaattttgct 15960 ctcaacatac aatgctagtt aaacagggtg atgattatgt gtaccttcct tacccagatc 16020 catcaagaat cctaggtgcc ggttgttttg tagatgatat cgtaaaaaca gatggtacac 16080 ttatgattga acggttcgtg tctttagcta tagatgctta cccacttact aaacatccta 16140 atcaggagta tgctgatgtc tttcatttgt acttacaata catacgtaag ctacatgatg 16200 agttaacagg acacatgtta gacatgtatt ctgttatgct tactaatgat aacacttcaa 16260 ggtattggga acctgagttt tatgaggcta tgtacacacc gcatacagtc ttacaagctg 16320 ttggtgcttg tgttctttgc aattcacaga cttcattaag atgtggtgct tgcatacgta 16380 gaccattctt atgttgtaaa tgctgttacg accatgtcat ctcaacatca cataaattag 16440 tcttgtctgt taatccgtat gtttgcaatg ctccaggttg tgatgtcaca gatgtgactc 16500 aactttactt aggaggtatg agctattact gtaagtcaca taaaccaccc attagttttc 16560 cattgtgtgc taatggacaa gtttttggtc tctacaagaa tacatgtgtt ggtagcgata 16620 atgttactga ctttaatgca attgcaacat gtgactggac aaatgctggt gattacattt 16680 tagctaacac ctgtactgaa agactcaagc tttttgcagc agaaacgctc aaagctactg 16740 aggagacatt taaactgtct tatggtattg ctactgtacg tgaagtgctg tctgacagag 16800 aattacatct ttcatgggaa gttggtaaac ctagaccacc acttaaccga aattatgtct 16860 ttactggtta tcgtgtaact aaaaacagta aagtgcaaat cggagagtac acctttgaaa 16920 aaggtgacta tggtgatgct gttgtttacc gaggtacaac aacttacaaa ctcaacgttg 16980 gtgattattt tgtgctgaca tcacatacag taatgccatt aagtgcacct acactagtgc 17040 cacaagagca ctatgttaga attactggct tatacccaac actcaatatc tcagatgagt 17100 tttctagcaa tgttgcaaat tatcaaaagg ttggtatgca aaagtattct acactccagg 17160 gaccacctgg tactggtaaa agtcattttg ctattggtct agctctctac tacccttctg 17220 ctcgcatagt atatacagct tgctctcatg cagctgttga tgcactatgt gagaaggcat 17280 taaaatattt gcccatagac aaatgtagta gaattatacc tgcacgtgct cgtgtagagt 17340 gttttgataa attcaaggtg aattcaacat tagaacagta tgtcttttgt actgtaaatg 17400 cattgcctga gacgacagca gatatagttg tctttgatga aatttcaatg gccacaaatt 17460 atgatttgag tgttgtcaat gccagattac gtgctaagca ctatgtgtac attggtgatc 17520 ctgctcaatt acctgcacca cgcacattac taactaaggg tacactagaa ccagaatatt 17580 tcaattcagt gtgtagactt atgaaaacta taggtccaga catgttcctc ggaacttgtc 17640 gtagatgtcc tgctgaaatt gttgacactg tgagtgcttt ggtttatgat aataagctta 17700 aggcacataa agacaaatca gctcaatgct ttaaaatgtt ctacaagggt gttatcacgc 17760 atgatgtttc atctgcaatt aacaggccac aaataggcgt ggtaagagaa ttccttacac 17820 gtaaccctgc ttggagaaaa gctgtcttta tttcacctta caattcccag aatgctgtag 17880 cctcaaagat tttgggacta ccaactcaaa ctgttgattc atcacagggc tcagaatatg 17940 actatgtcat attcactcaa accactgaaa cagctcactc ttgtaatgta aacagattca 18000 acgttgctat taccagagca aaagtaggca tactttgcat aatgtctgat agagaccttt 18060 atgacaagtt gcaatttaca agtcttgaaa ttccacgtag gaatgtggca actttacaag 18120 ctgaaaatgt aacaggactc tttaaagatt gtagtaaggt aatcactggg ttacatccta 18180 cacaggcacc tacacactta agtgttgata ctaaattcaa aactgaaggt ttatgtgttg 18240 acatacctgg catacctaag gacatgacct atagaagatt aatctctatg atgggtttca 18300 aaatgaatta ccaggttaat ggttacccta acatgtttat cacccgcgaa gaagctataa 18360 gacatgtacg tgcatggatt ggcttcgatg tcgaaggttg tcatgctact agagaagctg 18420 ttggtaccaa tttaccttta cagctaggtt tttctacagg tgttaaccta gttgctgtac 18480 ctacaggtta tgttgataca cctaataata cagatttttc cagagttagt gctaaaccac 18540 cgcctggaga tcaatttaaa cacctcatac cacttatgta caaaggactt ccttggaatg 18600 tagtgcgtat aaagattgtc caaatgttaa gtgacacact taaaaatctc tctgacagag 18660 tcgtatttgt cttatgggca catggctttg agttgacatc tatgaagtat tttgtgaaga 18720 tcggacctga gcgcacatgt tgtctatgtg atagacgtgc tacatgcttt tccactgctt 18780 cagacactta tgcctgttgg catcattcta ttggatttga ttacgtctat aatccgttta 18840 tgattgatgt tcaacaatgg ggttttacag gtaacctaca aagcaaccat gatctgtatt 18900 gtcaagtcca tggtaatgca catgtagcta gttgtgatgc aatcatgact aggtgtctag 18960 ctgtccacga gtgctttgtt aagcgtgttg actggactat tgaatatcct ataatcggtg 19020 atgaactgaa gattaatgcg gcttgtagaa aggttcaaca catggttgtt aaagctgcat 19080 tattagcaga caaattccca gttcttcacg acattggtaa ccctaaagct attaagtgtg 19140 tacctcaagc tgatgtagaa tggaagttct atgatgcaca gccttgtagt gacaaagctt 19200 acaaaataga agaactgttc tattcttatg ccacacattc tgacaaattc acagatggtg 19260 tatgcctatt ttggaattgc aatgtcgata gatatcctgc taattccatt gtttgtagat 19320 ttgacactag agtgctatct aaccttaact tgcctggttg tgatggtggc agtttgtatg 19380 taaataagca tgcattccac acaccagctt ttgataaaag tgcttttgtt aatctaaagc 19440 aacttccatt tttctattac tctgacagtc catgtgagtc tcatggaaaa caagtagtgt 19500 cagatataga ttatgtacca ctaaagtctg ctacgtgtat aacacgttgc aatttaggtg 19560 gtgctgtctg tagacatcat gctaatgagt acagattgta tctcgatgct tataacatga 19620 tgatctcagc tggctttagc ttgtgggttt acaaacaatt tgatacctat aacctctgga 19680 acacttttac aagacttcag agtttagaaa atgtggcttt taatgttgta aataagggac 19740 actttgatgg acaacagggt gaagtaccag tttctatcat taacaacact gtttacacaa 19800 aagttgatgg tgttgatgta gaattgtttg agaacaaaac cacattacct gttaatgtag 19860 catttgagct ttgggctaag cgcaacatta aaccagtacc agaggtgaaa atactcaata 19920 atttgggtgt ggacattgct gctaatactg tgatctggga ctacaaaaga gatgctccag 19980 cacatatatc tactattggt gtttgttcta tgactgacat agccaagaaa ccaactgaaa 20040 cgatttgtgc accactcact gtcttttttg atggtagagt tgatggtcaa gtagacttat 20100 ttagaaatgc ccgtaatggt gttcttatta cagaaggtag tgttaaaggt ttacaaccat 20160 ctgtaggtcc caaacaagct agtcttaatg gagtcacatt aattggagaa gccgtaaaaa 20220 cacagttcaa ttattacaag aaagtggatg gtgttgtcca acaattacct gaaacttact 20280 ttactcagag tagaaactta caggaattta agcccaggag tcaaatggaa attgatttct 20340 tagaacttgc tatggatgaa ttcattgaac ggtataaatt agaaggctat gccttcgaac 20400 atatcgttta tggagatttt agtcatagtc agttaggtgg tttacatcta ctgattggac 20460 tagctaaacg ttttaaggaa tcaccttttg aacttgaaga ttttattcct atggacagta 20520 cagttaaaaa ctacttcata acagatgcgc aaacaggttc atctaagtgt gtgtgttctg 20580 ttattgatct tttacttgat gacttcgttg aaataataaa gtcccaagat ttatctgtag 20640 tttctaaggt tgtcaaagtg actattgact atacagaaat ctcatttatg ctttggtgta 20700 aagatggcca tgtagaaaca ttttacccaa aattacaatc tagtcaagcg tggcaaccgg 20760 gtgttgctat gcctaatctt tacaaaatgc aaagaatgct attagaaaag tgtgaccttc 20820 aaaattatgg tgatagtgca acattaccta aaggcataat gatgaatgtc gcaaaatata 20880 ctcaactgtg tcaatattta aacacactga cattagctgt accctataat atgagagtta 20940 tccattttgg tgctggttct gataaaggag ttgcaccagg tacagctgtt ttaagacaat 21000 ggttgcctac aggtacgctg cttgtcgatt cagatcttaa tgactttgtc tctgatgcag 21060 attcaacttt gattggtgat tgtgcaactg tacatacagc taataaatgg gatctcatta 21120 ttagtgatat gtacgaccct aagactaaga atgtcacaaa agaaaacgac tctaaagagg 21180 gttttttcac ttacatttgt gggtttatac aacaaaagct agctcttgga ggttccgtgg 21240 ctataaagat aacagaacat tcttggaatg ctgatcttta taagctcatg ggacacttcg 21300 catggtggac agcctttgtt actaatgtga atgcgtcatc atctgaagca tttttaatcg 21360 gatgtaacta ccttggcaaa ccacgcgaac aaatagatgg ttatgtcatg catgcaaatt 21420 acatattttg gaggaataca aatccaattc agctttcttc ttattcttta ttcgacatga 21480 gtaaattccc ccttaaatta aggggtactg ctgttatgtc tttaaaagaa ggtcaaatca 21540 atgatatgat tctctctctt cttagtaaag gtagacttat aattagagaa aacaacagag 21600 ttgttatttc tagtgatgtt cttgttaaca actaaacgaa caatgtttgt ttttcttgtt 21660 ttattgccac tagtctctag tcagtgtgtt aatcttacaa ccagaactca attaccccct 21720 gcatacacta attctttcac acgtggtgtt tattaccctg acaaagtttt cagatcctca 21780 gttttacatt caactcagga cttgttctta cctttctttt ccaatgttac ttggttccat 21840 gctatacatg tctctgggac caatggtact aagaggtttg ataaccctgt cctaccattt 21900 aatgatggtg tttactttgc ttccactgag aagtctaaca taataagagg ctggattttt 21960 ggtactactt tagattcgaa aacccagtcc ctacttattg ttaataacgc tactaatgtt 22020 gttatcaaag tctgtgaatt tcaattttgt aacgatccat ttttgggtgt ttattaccac 22080 aaaaacaaca aaagttggat ggaaagtgag ttcagagttt attctagtgc gaataattgc 22140 acttttgaat acgtctctca gccttttctt atggaccttg aaggaaaaca gggtaatttc 22200 aaaaatctta gggaatttgt gttcaagaat attgatggtt acttcaagat atactctaag 22260 cacacgccta ttaatttagt gcgtgatctc cctcagggtt tttcggcttt agaaccattg 22320 gtagatttgc caataggtat taacatcact aggtttcaaa ctttacttgc tttacataga 22380 agttatttaa ctcctggtga ttcttcttca ggttggacag ctggtgctgc agcttattat 22440 gtgggttatc ttcaacctag gacttttcta ctgaagtaca atgaaaatgg aaccattaca 22500 gatgctgtag actgtgcact tgaccctctc tcagaaacaa agtgtacgtt gaaatccttc 22560 actgtagaaa aaggaatcta tcaaacttct aactttagag tccaaccaac agaatctatt 22620 gttagatttc ctaacatcac aaacttgtgc ccttttggtg aagtttttaa cgccaccaga 22680 tttgcatctg tttatgcttg gaacaggaag agaatcagca actgtgttgc tgattattct 22740 gtcctgtata attccgcatc attttccact tttaagtgtt atggagtgtc tcctactaaa 22800 ttaaatgatc tctgctttac taatgtctat gcagattcat ttgtaattag aggtgatgaa 22860 gtcagacaaa tcgctccagg gcaaactgga aagattgctg attataacta caaattacca 22920 gatgatttta caggctgcgt tatagcttgg aattctaaca atcttgattc taaggttggt 22980 ggtaattata attacctgta cagattgttt aggaagtcta atctcaaacc ttttgagaga 23040 gatatttcaa ctgaaatcta tcaggccggt agcacacctt gtaatggtgt tgaaggtttt 23100 aattgttact ttcctctgca atcatatggt ttccaaccca ctaatggtgt tggttaccaa 23160 ccatacagag tagtagtact ttcttttgaa cttctacatg caccagcaac tgtttgtgga 23220 cctaaaaagt ctactaattt ggttaagaac aagtgtgtca atttcaactt caatggttta 23280 acaggcacag gtgttcttac tgagtctaac aaaaagtttc tgcctttcca acaatttggc 23340 agagacattg ctgacactac tgatgctgtt cgtgatccac aaacacttga gattcttgac 23400 attacaccat gttcttttgg tggtgtcagt gttataacac caggaacaaa tacttctaac 23460 caggttgctg ttctttatca ggatgttaac tgcacagaag tccctgttgc tattcatgca 23520 gatcaactta ctcctacttg gcgtgtttat tctacaggtt ctaatgtttt tcaaacacgt 23580 gcaggctgtt taataggggc tgaacatgtc aacaactcat atgagtgtga catacccatt 23640 ggtgcaggta tatgcgctag ttatcagact cagactaatt ctcctcggag agcaagaagt 23700 gtagctagtc aatccatcat tgcctacact atgtcacttg gtgcagaaaa ttcagttgct 23760 tactctaata actctattgc catacccaca aattttacta ttagcgttac cacagaaatt 23820 ctaccagtgt ctatgaccaa gacatcagta gattgtacaa tgtacatttg tggtgattca 23880 actgaatgca gcaatctttt gttgcaatat ggcagttttt gtacacaatt aaaccgtgct 23940 ttaactggaa tagctgttga acaagacaaa aacacccaag aagtttttgc acaagtcaaa 24000 caaatttaca agacaccacc aattaaagat tttggcggtt ttaattttag ccagatactg 24060 ccagatccat caaaaccaag caagaggtca tttattgaag atctactgtt caacaaagtg 24120 acacttgcag atgctggctt catcaaacaa tatggtgatt gccttggtga tattgctgct 24180 agagacctca tttgtgcaca aaagtttaac ggccttactg ttttgccacc tttgctcaca 24240 gatgaaatga ttgctcaata cacttctgca ctgttagcag gtacaatcac ttctggttgg 24300 acttttggtg caggtgctgc attacaaata ccatttgcta tgcaaatggc ttataggttt 24360 aatggtattg gagttacaca gaatgttctc tatgagaacc aaaaattgat tgccaaccaa 24420 tttaatagtg ctattggcaa aattcaagac tcactttctt ccacagcaag tgcacttgga 24480 aaacttcaag atgtggtcaa ccaaaatgca caagctttaa acacgcttgt taaacaactt 24540 agctccaatt ttggtgcaat ttcaagtgtt ttaaacgaca tcctttcacg tcttgacaaa 24600 gttgaggctg aagtgcaaat tgataggttg atcacaggca gacttcaaag tttgcagaca 24660 tatgtgactc aacaattaat tagagctgca gaaatcagag cttctgctaa tcttgctgct 24720 actaaaatgt cagagtgtgt acttggacaa tcaaaaagag ttgacttttg cggaaagggc 24780 tatcatctta tgtcatttcc tcagtcagca cctcatggtg tcgtcttttt gcatgtgact 24840 tatgtccctg cacaagaaaa gaacttcaca actgctcctg ccatttgtca tgatggaaaa 24900 gcacactttc ctcgtgaagg tgtctttgtt tcaaatggca cacactggtt tgtaacacaa 24960 aggaattttt atgaaccaca aatcattact acagacaaca catttgtgtc tggtaactgt 25020 gatgttgtaa taggaattgt caacaacaca gtttatgatc ctttgcaacc tgaattagac 25080 tcattcaagg aggagcttga taaatacttc aagaaccata cctcaccaga tgttgattta 25140 ggtgacatct ctggcattaa tgcttcagtt gtaaacattc agaaagaaat cgaccgcctc 25200 aatgaggttg ccaagaattt aaatgaatct ctcatcgatc tccaagaact tggaaagtat 25260 gagcagtata taaaatggcc atggtacatt tggctaggtt ttatagctgg cttgattgcc 25320 atagtaatgg tgacaattat gctttgctgt atgaccagtt gctgtagttg tctcaagggc 25380 tgttgttctt gtggatcctg ctgcaaattt gacgaggacg actctgagcc agtgctcaaa 25440 ggagtcaaat tacattacac ataaacgaac ttatggattt gtttatgaga atcttcacaa 25500 ttggaactgt aactttgaag caaggtgaaa tcaaggatgc tactccttca gattttgtta 25560 gagctactgc aacgataccg atacaagcat cacttccttt cggatggctt attgttggcg 25620 ttgcacttct tgctgttttt cagagcgctt ccaaaatcat aaccctcaaa aagagatggc 25680 aactagcact ctccaagggt gttcactttg tttgcaactt gctgttgttg tttgtaacag 25740 tttactcaca tcttttgctt gttgctgctg gccttgaagc cccttttctc tatctttatg 25800 ctttagtcta cttcttgcag agtataaact ttgtacgcat aataatgagg ctttggcttt 25860 gctggaaatg ccgttccaaa aacccattac tttatgatgc caactatttt ctttgctggc 25920 atactaattg ttacgactat tgtatacctt acaatagtgt aacttcttca attgtcatta 25980 cttcaggtga tggcacaaca agtcctattt ctgaacatga ctaccagatt ggtggttata 26040 ctgaaaaatg ggaatctgga gtaaaagact gtgttgtatt acacagttac ttcacttcag 26100 actattacca gctgtactca actcaattga gtacagacac tggtgttgaa catgttacct 26160 tcttcatcta caataaaatc gttgatgagc ctgaagaaca tgtccaaatt cacacaatcg 26220 acgtttcatc cggagttgtt aatccagtaa tggaaccaat ttatgatgaa ccgacgacga 26280 ctactagcgt gcctttgtaa gcacaagctg atgagtacga acttatggca gattccaacg 26340 gtactattac cgttgaggag ctgaaaaagc tccttgaaca atggaaccta gtaataggtt 26400 tcctattcct tacatggatt tgcctgctgc aatttgccta tgccaacagg aataggtttt 26460 tgtacatcat taagttgatt ttcctctggc tgttatggcc agtaacttta gcttgttttg 26520 tgcttgctgc tgtttacaga ataaattgga tcaccggtgg aattgctatt gcaatggctt 26580 gtcttgtagg attgatgtgg ctaagctact tcattgcttc tttcagactg tttgcgcgta 26640 cgcgttccat gtggtcattc aatccagaaa ctaacattct tctcaacgtg ccactccatg 26700 gaactattct gactagaccg cttctagaaa gtgaactcgt aatcggagct gttatccttc 26760 gtggacatct tcgtattgct ggacatcatc taggacgctg tgacatcaag gatctaccta 26820 aagaaatcac tgttgctaca tcacgaacgc tttcttatta caaattggga gcttcacagc 26880 gtgtagcagg tgattcaggt tttgctgcat atagtcgcta caggattggc aactataaat 26940 taaacacaga ccattccagt agcagtgaca atattgcttt gcttgtacag taaacgaaca 27000 tgaaaattat tcttttcttg gcactgataa cactcgctac ttgtgagctt tatcactacc 27060 aagagtgtgt tagaggtaca acagtacttt taaaagaacc ttgctcgtcg ggaacatacg 27120 agggcaattc accatttcat cctctagctg ataacaaatt tgcactgact tgctttagca 27180 ctcaatttgc ttttgcttgt cctgacggcg taaaacacgt ctatcagtta cgtgccagat 27240 cagtttcacc taaactgttc atcagacaag aggaagttca agaactttac tctccaattt 27300 ttcttattgt tgcggcaata gtgtttataa cactttgctt cacactcaaa agaaagacag 27360 aatgattgaa ctttcattaa ttgacttcta tttgtgcttt ttagcctttc tgctattcct 27420 tgttttaatt atgcttatta tcttttggtt ctcacttgaa ctgcaagatc ataatgaaac 27480 ttgtcacgcc taaacgaaca tgaaatttct tgttttctta ggaatcatca caactgtagc 27540 tgcatttcac caagaatgta gtttacagtc atgtactcaa catcaaccat atgtagttga 27600 tgacccgtgt cctattcact tctattctaa atggtatatc agagtaggag ctagaaaatc 27660 agcaccttta attgaattgt gcgtggatga ggctggttct aaatcaccca ttcagtacat 27720 cgatatcggt aattatacag tttcctgttt accttttaca attaactgcc aggaacctaa 27780 attgggtagt cttgtagtgc gttgttcgtt ctacgaggac tttttagagt atcatgacgt 27840 tcgtgttgtt ttagatttca tctaaacgaa caaactaaaa tgtctgataa tggacctcaa 27900 aatcagcgaa atgcacctcg cattacgttt ggtggaccat cagattcaac tggcagtaac 27960 cagaatggag aacgaagtgg tgcgcgatca aaacaacgcc gcccgcaagg tttacccaat 28020 aatactgcgt cttggttcac cgctctcact caacatggca aggaagattt aaaattccct 28080 cgaggacaag gcgttccaat taacaccaat agcagtccag atgaccaaat tggctactac 28140 cgccgcgcca caagacgaat tcgtggtggt gatggtaaaa tgaaagatct cagtccaaga 28200 tggtatttct actatctagg aactgggcca gaagctggac ttccttatgg tgctaacaaa 28260 gatggcatca tatgggttgc aactgaggga gccttgaata caccaaaaga tcacattggc 28320 accagaaatc ctgctaacaa tgctgcaatc gtgctacaac ttcctcaagg aacaacatta 28380 ccaaaaggtt tttacgcaga agggtctaga ggtggaagtc aagcctcttc tagatcatca 28440 tcacgtagtc gcaacagttc aagaaattca actccaggtt caagtagagg aacttctcct 28500 gctagaatgg ctggaaatgg aggtgatgct gctcttgctt tgttactact tgacagattg 28560 aaccagcttg agagcaaaat gtctggtaaa ggccaacaac aacaaggcca aactgtcact 28620 aagaaatctg ctgctgaggc ttctaagaag cctagacaaa aacgtactgc cactaaagca 28680 tacaatgtaa cacaagcttt cggcagacgt ggtccagaac aaactcaagg aaattttggg 28740 gatcaggaac taatcagaca aggaactgat tacaaacatt ggccgcaaat tgcacaattt 28800 gctccttctg cttcagcgtt ctttggaatg tcgagaattg gaatggaagt cacaccttcg 28860 ggaacatggt tgacctatac aggtgccatc aaattggatg acaaagatcc aaatttcaaa 28920 gatcaagtca ttttgctgaa taagcatatt gacgcataca aaacattccc accaacagag 28980 cctaaaaagg acaaaaagaa gaaggctgat gaaactcaag ccttaccgca gagacagaag 29040 aaacagcaaa ctgtgactct tcttcctgct gcagatttgg atgatttctc caaacaattg 29100 caacaatcca tgagcagtgc tgactcaact caggcctaaa ctcatgcaga ccacacaagg 29160 cagatgggct atataaacgt tttcgctttt ccgtttacga tatatagtct actcttgtgc 29220 agaatgaatt ctcgtaacta catagcacaa gtagatgtag ttaactttaa tctcacatag 29280 caatctttaa tcagtgtgta acattaggga ggacttgaaa gagccaccac attttcaccg 29340 aggccacgcg gagtacgatc gagtgtacag tgaacaatgc tagggagagc tgcctatatg 29400 gaagagccct aatgtgtaaa attaatttta gtagtgctat ccccatgtga ttttaatagc 29460 ttcttaggag aatgacaaaa aaaaacaaaa aaaa 29494 <210> 42 <211> 29348 <212> DNA <213> Artificial Sequence <220> <223> Synthesis optimized sequence E-protein and ORF8 double deletion <400> 42 caaatataac gaaaggctca gtcgaaagac tgggcctttc gttttatctg ttgtttgtcg 60 taatacgact cactataggg attaaaggtt tataccttcc caggtaacaa accaaccaac 120 tttcgatctc ttgtagatct gttctctaaa cgaactttaa aatctgtgtg gctgtcactc 180 ggctgcatgc ttagtgcact cacgcagtat aattaataac taattactgt cgttgacagg 240 acacgagtaa ctcgtctatc ttctgcaggc tgcttacggt ttcgtccgtg ttgcagccga 300 tcatcagcac atctaggttt cgtccgggtg tgaccgaaag gtaagatgga gagccttgtc 360 cctggtttca acgagaaaac acacgtccaa ctcagtttgc ctgttttaca ggttcgcgac 420 gtgttagtac gtggttttgg agattcagtg gaagaagtct tatcagaggc acgtcaacat 480 cttaaagatg gcacttgtgg cttagtagaa gttgaaaaag gcgttttgcc tcaacttgaa 540 cagccctatg tgttcatcaa acgttctgat gctagaactg cacctcatgg tcatgttatg 600 gttgagctgg tagcagaatt agaaggtatt cagtacggtc gtagtggtga gacattaggt 660 gttttagttc ctcatgtggg cgaaatacca gtggcttacc gcaaagttct tcttagaaag 720 aacggtaata aaggagctgg tggccatagt tacggcgctg atttaaagtc atttgactta 780 ggcgacgagc ttggcactga tccttatgaa gatttccaag aaaactggaa cactaaacat 840 agcagtggtg ttacccgtga actcatgcgt gagttaaatg gaggtgcata cactcgctat 900 gtcgataaca acttctgtgg acctgatggt taccctcttg agtgcattaa agaccttcta 960 gcacgtgctg gtaaagcttc atgcactttg tccgaacaac tggactttat tgacactaag 1020 aggggtgtat actgctgccg tgaacatgag catgaaattg cttggtacac ggaacgttct 1080 gaaaagagct atgaattgca gacacctttt gaaattaaac tggcaaagaa atttgacacc 1140 ttcaatgggg aatgtccaaa ttttgtattt cccctcaatt ccataatcaa gactattcaa 1200 ccaagggttg aaaagaaaaa gcttgatggc tttatgggta gaattcgatc tgtctatcca 1260 gttgcgtcac caaatgaatg caaccaaatg tgcctttcaa ctctcatgaa gtgtgatcat 1320 tgtggtgaaa cttcatggca gacgggcgat tttgttaaag ccacttgcga attttgtggc 1380 actgagaatt tgactaaaga aggtgccact acttgtggtt acttacccca aaatgctgtt 1440 gttaaaattt actgtccagc atgtcacaat tcagaagtag gacctgagca tagtcttgcc 1500 gaataccata atgaatctgg cttgaaaacc attcttcgta agggtggtcg cactattgct 1560 tttggaggat gtgtgttctc ttatgttggt tgccataaca agtgtgctta ttgggttcca 1620 cgtgcttcag ctaacatagg ttgtaaccat acaggtgttg ttggagaagg ttccgaaggt 1680 cttaatgaca accttcttga aatactccaa aaagagaaag tcaacatcaa tattgttggt 1740 gactttaaac ttaatgaaga gatcgccatt attttggcat ctttttctgc ttccacaagt 1800 gcttttgtgg aaactgtgaa aggtttggat tataaagcat tcaaacagat tgttgaatcc 1860 tgtggtaatt ttaaggttac aaagggaaaa gctaaaaaag gtgcctggaa tattggtgaa 1920 cagaaatcaa tactgagtcc tctttatgca tttgcatcag aggctgctcg tgttgtacga 1980 tcaattttct cccgcactct tgaaactgct caaaattctg tgcgtgtttt acagaaggcc 2040 gctataacaa tactagatgg aatttcacag tattcactga gactcattga tgctatgatg 2100 ttcacatctg atttggctac taacaatcta gttgtaatgg cctacattac aggtggtgtt 2160 gttcagttga cttcgcagtg gctaactaac atctttggca ctgtttatga aaaactcaaa 2220 cccgtccttg attggcttga agagaagttt aaggaaggtg tagagtttct tagagacggt 2280 tgggagattg ttaaattcat ctcaacctgt gcttgtgaaa ttgtcggtgg acaaattgtc 2340 acctgtgcta aggaaattaa ggagagtgtt cagacattct ttaagcttgt aaacaagttt 2400 ttggctttgt gtgctgactc tatcattatt ggtggagcta aacttaaagc cttgaattta 2460 ggtgaaacat ttgtcacgca ctcaaaggga ttgtacagaa agtgtgttaa atccagagaa 2520 gaaactggcc tactcatgcc tctaaaagcc ccaaaagaaa ttatcttctt agagggagaa 2580 acacttccca cagaagtgtt aacagaggaa gttgtcttga aaactggtga tttacaacca 2640 ttagaacaac ctactagtga agctgttgaa gctccattgg ttggtacacc agtttgtatt 2700 aacgggctta tgttgctcga aatcaaagac acagaaaagt actgtgccct tgcacctaat 2760 atgatggtaa caaacaatac cttcacactc aaaggcggtg caccaacaaa ggttactttt 2820 ggtgatgaca ctgtgataga agtgcaaggt tacaagagtg tgaatatcac ttttgaactt 2880 gatgaaagga ttgataaagt acttaatgag aagtgctctg cctatacagt tgaactcggt 2940 acagaagtaa atgagttcgc ctgtgttgtg gcagatgctg tcataaaaac tttgcaacca 3000 gtatctgaat tacttacacc actgggcatt gatttagatg agtggagtat ggctacatac 3060 tacttatttg atgagtctgg tgagtttaaa ttggcttcac atatgtattg ttctttctac 3120 cctccagatg aggatgaaga agaaggtgat tgtgaagaag aagagtttga gccatcaact 3180 caatatgagt atggtactga agatgattac caaggtaaac ctttggaatt tggtgccact 3240 tctgctgctt tacaacctga agaagaacaa gaagaagatt ggttagatga tgatagtcaa 3300 caaactgttg gtcaacaaga cggcagtgag gacaatcaga caactactat tcaaacaatt 3360 gttgaggttc aacctcaatt agagatggaa cttacaccag ttgttcagac tattgaagtg 3420 aatagtttta gtggttatct taaacttact gacaatgtat acatcaagaa tgcagacatt 3480 gtggaagaag ctaaaaaggt aaaaccaaca gtggttgtta atgcagccaa tgtttacctt 3540 aaacatggag gaggtgttgc aggagcctta aataaggcta ctaacaatgc catgcaagtt 3600 gaatctgatg attacatagc tactaatgga ccacttaaag tgggtggtag ttgtgtttta 3660 agcggacaca atcttgctaa acactgttta catgttgtcg gcccaaatgt taacaaaggt 3720 gaagatattc aacttcttaa gagtgcttat gaaaatttta accagcacga agttctactt 3780 gcaccattat tatcagctgg tatttttggt gctgacccta tacattcttt aagagtttgt 3840 gtagatactg ttcgcacaaa tgtctactta gctgtctttg ataaaaatct ctatgacaaa 3900 cttgtttcaa gctttttgga aatgaagagt gaaaagcaag ttgaacaaaa gatcgctgag 3960 attcctaaag aggaagttaa gccatttata actgaaagta aaccttcagt tgaacagaga 4020 aaacaagatg ataagaagat caaagcttgt gttgaagaag ttacaacaac tctggaagaa 4080 actaagttcc tcacagaaaa cttgctcctt tatatcgaca ttaatggcaa tcttcatcca 4140 gattctgcca ctcttgttag tgacattgac atcactttct taaagaaaga tgctccatat 4200 atagtgggtg atgttgttca agagggtgtt ttaactgctg tggttatacc tactaaaaag 4260 gctggtggca ctactgaaat gctagcgaaa gctttgagaa aagtgccaac agacaattat 4320 ataaccactt acccgggtca gggtttaaat ggttacactg tagaggaggc aaagacagtg 4380 cttaaaaagt gtaaaagtgc cttttacatt ctaccatcta ttatctctaa tgagaagcaa 4440 gaaattcttg gaactgtttc ttggaatttg cgagaaatgc ttgcacatgc agaagaaaca 4500 cgcaaattaa tgcctgtctg tgtggaaact aaagccatag tttcaactat acagcgtaaa 4560 tataagggta tcaagataca agagggtgtg gttgattatg gtgctagatt ttacttttac 4620 accagtaaaa caactgtagc gtcacttatc aacacactta acgatctaaa tgaaactctt 4680 gttacaatgc cacttggcta tgtaacacat ggcttaaatt tggaagaagc tgctcggtat 4740 atgagatctc tcaaagtgcc agctacagtt tctgtttctt cacctgatgc tgttacagcg 4800 tataatggtt atcttacttc ttcttctaaa acacctgaag aacattttat tgaaaccatc 4860 tcacttgctg gttcctataa agattggtcc tattctggac aatctacaca actaggtata 4920 gaatttctta agagaggtga taaaagtgta tattacacgt ccaatcctac cacattccac 4980 ctagatggtg aagttatcac ctttgacaat cttaagacac ttctttcttt gagagaagtg 5040 aggactatta aggtgtttac aacagtagac aacattaacc tccacacgca agttgtggac 5100 atgtcaatga catatggaca acagtttggt ccaacttatt tggatggagc tgatgttact 5160 aagataaaac ctcataactc acatgaaggt aaaacatttt acgttttgcc taatgatgac 5220 actctacgtg ttgaggcttt tgagtactac cacacaactg atcctagttt tctgggtagg 5280 tacatgtcag cattaaatca cactaaaaag tggaaatacc cacaagttaa tggtttaact 5340 tcgattaaat gggcagataa caactgttat cttgccactg cattgttaac actccaacaa 5400 atagagttga agtttaatcc acctgctcta caagatgctt attacagagc aagggctggt 5460 gaagctgcta acttttgtgc acttatctta gcctactgta ataagacagt aggtgagtta 5520 ggtgatgtta gagaaacaat gagttacttg tttcaacatg ccaatttaga ttcttgcaaa 5580 agagtcttga acgtggtgtg taaaacttgt ggacaacagc agacaaccct taagggtgta 5640 gaagctgtta tgtacatggg cacactttct tatgaacaat tcaagaaagg tgttcagata 5700 ccttgtacgt gtggtaaaca agctacaaaa tatctagtac aacaggagtc accttttgtt 5760 atgatgtcag caccacctgc tcagtatgaa cttaagcatg gtacatttac ttgtgctagt 5820 gagtacactg gtaattacca gtgtggtcac tataagcata taacttctaa ggaaactttg 5880 tattgcatag acggtgcttt acttacaaag tcctcagaat acaaaggtcc tattacggat 5940 gttttctaca aagaaaacag ttacacaaca accataaaac cagttactta taagttggat 6000 ggtgttgttt gtacagaaat tgaccctaag ttggacaatt attataagaa ggacaactct 6060 tatttcacag agcaaccaat tgatcttgta ccaaaccaac catatccaaa cgcaagcttc 6120 gataatttta agttcgtatg cgataatatc aaatttgctg atgatctcaa ccagttaact 6180 ggttataaga aacctgcttc aagagagctt aaagttacat ttttccctga cttaaatggt 6240 gatgtggtgg ctattgatta taaacactac acaccctctt ttaagaaagg agctaaattg 6300 ttacataagc ctattgtttg gcatgttaac aatgcaacta ataaagccac gtataaacca 6360 aatacctggt gtatacgttg tctttggagc acaaaaccag ttgaaacatc aaattcgttt 6420 gatgtactga agtcagagga cgcgcaggga atggataatc ttgcatgtga agatctaaaa 6480 ccagtctctg aagaagtagt ggaaaatcct accatacaga aagacgttct tgagtgtaat 6540 gtgaaaacta ccgaagttgt aggagacatt atacttaaac cagcaaataa tagtttgaag 6600 atcacagaag aggttggcca cacagatcta atggctgctt atgtagacaa ttctagtctt 6660 actattaaga aacctaatga actctctaga gtattaggtt tgaaaaccct tgctactcat 6720 ggtttagctg ctgttaatag tgtcccttgg gatactatag ctaattatgc taagcctttt 6780 cttaacaaag ttgttagtac aactactaac atagttacac ggtgtcttaa tcgtgtttgt 6840 actaattata tgccttactt ctttacttta ttgctacaat tgtgtacttt tactagaagt 6900 acaaattcta gaatcaaggc atctatgccg actactatag caaagaatac tgttaagagt 6960 gtcggtaaat tttgtctaga ggcttcattt aattatctca agtcacctaa cttttctaag 7020 ctgataaaca ttatcatctg gtttttgcta ttaagtgttt gcctaggttc tttaatctac 7080 tcaaccgctg ctttaggtgt tttaatgtct aatttaggca tgccttctta ctgtactggt 7140 tacagagaag gctatttgaa ctctactaat gtcactattg caacctactg tactggatct 7200 ataccttgta gtgtttgtct tagtggttta gattctttag acacctatcc ttctcttgaa 7260 actatacaga ttaccatttc atctttcaaa tgggatttaa ctgcttttgg cttagttgca 7320 gagtggtttt tggcatatat tcttttcact aggtttttct atgtacttgg attggctgca 7380 atcatgcaat tgtttttcag ctattttgca gtccatttta ttagtaactc ttggcttatg 7440 tggcttataa ttaatcttgt gcagatggcc ccgatttcag ctatggttag aatgtacatc 7500 ttctttgcct cattttatta tgtgtggaaa agttatgtgc atgttgtaga cggttgtaat 7560 tcatcaactt gtatgatgtg ttacaaacgt aatagagcaa caagagtcga atgtacaact 7620 attgttaatg gtgttagaag gtccttttat gtctatgcta atggaggtaa aggcttttgc 7680 aaactacaca attggaattg tgttaattgt gatacattct gtgctggtag tacatttatt 7740 agtgatgaag ttgcgagaga cttgtcacta cagtttaaaa gaccaataaa tcctactgac 7800 caatcttctt acatcgttga tagtgttaca gtgaagaatg gttccatcca tctttacttt 7860 gataaagctg gtcaaaagac ttatgaaaga cattctctct ctcattttgt taacttagac 7920 aacctgagag ctaataacac taaaggttca ttgcctatta atgttatcgt tttcgacggt 7980 aaatcaaaat gtgaagaatc atctgcaaaa tcagcgtctg tttactacag tcagcttatg 8040 tgtcaaccta tactgttact agatcaggca ttagtgtctg atgttggtga tagtgcggaa 8100 gttgcagtta aaatgtttga tgcttacgtt aatacgtttt catcaacttt taacgtacca 8160 atggaaaaac tcaaaacact agttgcaact gcagaagctg aacttgcaaa gaatgtgtcc 8220 ttagacaatg tcttatctac gtttatttca gcagctcggc aagggtttgt tgattcagat 8280 gtagaaacta aagatgttgt tgaatgtctt aaattgtcac atcaatctga catagaagtt 8340 actggcgata gttgtaataa ctatatgctc acctataaca aagttgaaaa catgacaccc 8400 cgtgaccttg gtgcttgtat tgactgtagt gctagacata ttaatgcgca ggtagcaaaa 8460 agtcacaaca ttgctttgat atggaacgtt aaagatttca tgtcattgtc tgaacaacta 8520 cgaaaacaaa tacgtagtgc tgctaaaaag aataacttac ccttcaagtt gacatgtgca 8580 actactagac aagttgttaa tgttgtaaca acaaagatag cacttaaggg tggtaaaatt 8640 gtgaataact ggttgaagca gcttattaaa gttacacttg tgttcctttt tgttgctgct 8700 attttctatc tgataacacc tgttcatgtc atgtctaaac atactgactt ttcaagtgaa 8760 atcataggat acaaggctat tgatggtggt gtcactcgtg acatagcatc tacagatact 8820 tgttttgcta acaaacatgc tgattttgac acatggttta gccagcgtgg tggtagttat 8880 actaatgaca aagcttgccc attgattgct gcagtcataa caagagaagt gggttttgtc 8940 gttcctggtt tgcctggaac gatattacgc acaactaatg gtgacttttt gcatttctta 9000 cctagagttt ttagtgcagt tggtaacatc tgttacacac catcaaaact tatagagtac 9060 actgactttg caacatcagc ttgtgttttg gctgctgaat gtacaatttt taaagacgct 9120 tctggtaagc cagtaccata ttgttatgat accaatgtac tagaaggttc tgttgcttat 9180 gaaagtttac gccctgacac acgttatgtg ctcatggatg gctctattat tcaatttcct 9240 aacacctacc ttgaaggttc tgtaagagtg gtaacaactt ttgattctga gtactgtagg 9300 cacggcactt gtgaaagatc agaagctggt gtttgtgtat ctactagtgg tagatgggta 9360 cttaacaacg attattacag atctttacca ggagttttct gtggtgtaga tgctgtaaat 9420 ttgcttacta acatgtttac accactaatt caacctattg gtgctttgga catatcagca 9480 tctatagtag ctggtggtat tgtagctatc gtagtaacat gccttgccta ctattttatg 9540 aggtttagac gtgcttttgg tgaatacagt catgtagttg cctttaatac tctcctattc 9600 cttatgtcat tcactgtact ctgtttaaca ccagtttact cattcttacc tggtgtttat 9660 tctgttattt acctgtactt gacattttat ctgactaatg atgtttcttt tctcgcacat 9720 attcagtgga tggttatgtt cacaccttta gtacctttct ggataacaat tgcttacatc 9780 atttgtattt ccacaaagca tttctattgg ttctttagta attacctaaa gagacgtgta 9840 gtctttaatg gtgtttcctt tagtactttt gaagaagctg cgctgtgcac ctttttgtta 9900 aataaggaga tgtatctaaa gttgcgtagt gatgtgctat tacctcttac gcaatataat 9960 agatacttag ctctttataa caagtacaag tatttcagtg gagcaatgga tacaactagc 10020 tacagagaag ctgcttgttg tcatctcgca aaggctctca atgacttcag taactcaggt 10080 tctgatgttc tttaccaacc accacaaacc tctatcacct cagctgtttt gcagagtggt 10140 tttagaaaaa tggcattccc atctggtaaa gttgagggtt gtatggtaca agtaacttgt 10200 ggtacaacta cacttaacgg tctttggctt gatgacgtag tttactgtcc aagacatgtg 10260 atctgcacct ctgaagatat gcttaaccct aattatgaag atctactcat ccgtaagtct 10320 aatcataact tcttggtaca ggctggtaat gttcaactca gggttattgg acattctatg 10380 caaaattgtg tacttaagct taaggttgat acagccaatc ctaagacacc taagtataag 10440 tttgttcgca ttcaaccagg acagactttt tcagtgttag cttgttacaa tggttcacca 10500 tctggtgttt accaatgtgc tatgaggccc aatttcacta ttaagggttc attccttaat 10560 ggttcatgtg gtagtgttgg ttttaacata gattatgact gtgtctcttt ttgttacatg 10620 caccatatgg aattaccaac tggagttcat gctggcacag acttagaagg taacttttat 10680 ggaccttttg ttgacaggca aacagcacaa gcagctggta cagatacaac tattacagtt 10740 aatgttcttg cttggttgta cgctgctgtt ataaatggag acaggtggtt tctcaatcga 10800 tttaccacaa ctcttaatga ctttaacctt gtggctatga agtacaatta tgaacctcta 10860 acacaagacc atgttgacat actaggacct ctttctgctc aaactggaat tgccgtttta 10920 gatatgtgtg cttcattaaa agaacttctg caaaatggta tgaatggacg taccatattg 10980 ggtagtgctt tattagaaga tgagtttaca ccttttgatg ttgttagaca atgctcaggt 11040 gttactttcc aaagtgcagt gaaaagaaca atcaagggta cacaccactg gttgttactc 11100 acaattttga cttcactttt agttttagtc cagagtactc aatggtcttt gttctttttc 11160 ttctacgaaa atgccttttt accttttgct atgggtatta ttgctatgtc tgcttttgca 11220 atgatgtttg tcaaacataa gcatgcattt ctctgtttgt ttttgttacc ttctcttgcc 11280 actgtagctt actttaatat ggtctacatg cctgctagtt gggtgatgcg tattatgaca 11340 tggttggata tggttgatac tagtttgtct ggttttaagc taaaagactg tgttatgtat 11400 gcatcagctg tagtgttact aatccttatg acagcaagaa ctgtgtatga tgatggtgct 11460 aggagagtgt ggacacttat gaatgtcttg acactcgttt ataaagttta ctatggcaac 11520 gctttagatc aagccatttc catgtgggct cttataatct ctgttacttc taactactca 11580 ggtgtagtta caactgtcat gtttttggcc agaggtattg tttttatgtg tgttgagtat 11640 tgccctattt tcttcataac tggtaataca cttcagtgta taatgctagt ctattgtttc 11700 ttaggctatt tttgtacttg ttacttcggc ctcttttgtt tactcaaccg ctactttaga 11760 ctgactcttg gtgtttatga ttacttagtg tctacacagg agtttagata tatgaattca 11820 cagggactac tcccacccaa gaatagcata gatgccttca aactcaacat taaattgttg 11880 ggtgttggtg gcaaaccttg tatcaaagta gccactgtac agtctaaaat gtcagatgta 11940 aagtgcacat cagtagtctt actctcagtt ttgcaacaac tcagagtaga atcatcatct 12000 aaattgtggg ctcaatgtgt ccagttacac aatgacattc tcttagctaa agatactact 12060 gaagcctttg aaaaaatggt ttcactactt tctgttttgc tttccatgca gggtgctgta 12120 gacataaaca agctttgtga agaaatgctg gacaacaggg caaccttaca agctatagcc 12180 tcagagttta gttcccttcc atcatatgca gcttttgcta ctgctcaaga agcttatgag 12240 caggctgttg ctaatggtga ttctgaagtt gttcttaaaa agttgaagaa gtctttgaat 12300 gtggctaaat ctgaatttga ccgtgatgca gccatgcaac gtaagttgga aaagatggct 12360 gatcaagcta tgacccaaat gtataaacag gctagatctg aggacaagag ggcaaaagtt 12420 actagtgcta tgcagacaat gcttttcact atgcttagaa agttggataa tgatgcactc 12480 aacaacatta tcaacaatgc aagagatggt tgtgttccct tgaacataat acctcttaca 12540 acagcagcca aactaatggt tgtcatacca gactacaaca catataagaa tacgtgtgat 12600 ggtacaacat ttacttatgc atcagcattg tgggaaatcc aacaggttgt agatgcagat 12660 agtaaaattg ttcagcttag tgaaattagt atggacaatt cacctaattt agcatggcct 12720 cttattgtaa cagctttaag ggccaattct gctgtcaaat tacagaataa tgagcttagt 12780 cctgttgcac taagacaaat gtcttgtgct gccggtacta cacaaactgc ttgcactgat 12840 gacaatgcgt tagcttacta caacacaaca aagggaggta ggtttgtact tgcactgtta 12900 tccgatttac aggatttgaa atgggctaga ttccctaaga gtgatggaac tggtactatc 12960 tatacagaac tggaaccacc ttgtaggttt gttacagaca cacctaaagg tcctaaagtg 13020 aagtatcttt acttcatcaa aggattaaac aacctaaata gaggtatggt acttggtagt 13080 ttagctgcca cagtacgttt acaagctggt aatgcaacag aagttcctgc taattcaact 13140 gtactttctt tctgtgcttt tgctgtagat gctgctaaag cttacaaaga ttatctagct 13200 agtgggggac aaccaatcac taattgtgtt aagatgttgt gtacacacac tggtactggt 13260 caggcaataa cagttacacc ggaagccaat atggatcaag aatcctttgg tggtgcatcg 13320 tgttgtctgt actgccgttg tcatatagat catccaaatc ctaaaggatt ttgtgactta 13380 aaaggtaagt atgtacaaat acctacaact tgtgctaatg accctgtggg ttttacactt 13440 aaaaacacag tctgtaccgt ctgcggtatg tggaaaggtt atggttgtag ttgtgatcaa 13500 ctccgcgaac ccatgcttca gtcagctgat gcacaatcgt ttttaaacgg gtttgcggtg 13560 taagtgcagc ccgtcttaca ccgtgcggca caggcactag tactgatgtc gtatatagag 13620 cttttgacat ctacaatgat aaagtagctg gttttgctaa gttcctaaaa actaattgtt 13680 gtcgcttcca agaaaaggac gaagatgaca atctcattga ttcttacttt gtagttaaga 13740 gacacacttt ctctaactac caacatgaag aaacaattta caacctgctt aaggattgtc 13800 cagctgttgc taaacatgac ttctttaagt ttagaataga cggtgacatg gtaccacata 13860 tatcacgtca acgtcttact aaatacacaa tggcagacct cgtctatgct ttaaggcatt 13920 ttgatgaagg taattgtgac acattaaaag aaatacttgt cacatacaat tgttgtgatg 13980 atgactactt caataaaaag gactggtatg attttgtaga aaacccagat atattacgcg 14040 tatacgccaa cttaggtgaa cgtgtacgcc aagctttgtt aaaaacagta cagttctgtg 14100 atgccatgcg aaatgctggt attgttggtg tactgacatt agataatcaa gatctcaatg 14160 gtaactggta tgactttggt gatttcatac aaaccacgcc aggtagtgga gttcctgttg 14220 tagactctta ttattcattg ctcatgccta tattaacctt gaccagggct ttaactgcag 14280 agtcacatgt tgacactgac ttaacaaagc cttacattaa gtgggatttg ttaaaatacg 14340 acttcacgga agagaggtta aaactctttg accgttattt taaatactgg gatcagacat 14400 accacccaaa ttgtgttaac tgtttggatg acagatgcat tctgcattgt gcaaacttta 14460 atgttctgtt ctctacagtg ttcccaccta caagttttgg accactagtg agaaaaatat 14520 ttgttgatgg tgttccattt gtagtttcaa ctggatacca cttcagagag ctaggtgttg 14580 tacataatca ggatgtaaac ttacatagct ctagacttag ttttaaggaa ttacttgtgt 14640 atgctgctga tcctgctatg catgctgctt ctggtaatct attactagat aaacgcacta 14700 cgtgcttttc agtagctgca cttactaaca atgttgcttt tcaaactgtc aaacccggta 14760 attttaacaa ggacttctat gactttgctg tgtctaaggg tttctttaag gaaggaagtt 14820 ctgttgaatt aaaacacttc ttctttgctc aggatggtaa tgctgctatc agcgattatg 14880 actactatcg ttataatcta ccaacaatgt gtgatatcag acaactacta tttgtagttg 14940 aagttgttga taagtacttt gattgttacg atggtggctg tattaatgct aaccaagtca 15000 tcgtcaacaa cctagacaaa tcagctggtt ttccatttaa taaatggggt aaggctagac 15060 tttattatga ttccatgagt tatgaggatc aagatgcact tttcgcatat acaaaacgta 15120 atgtcatccc tactataact caaatgaacc ttaagtatgc cattagtgca aagaatagag 15180 ctcgcaccgt agctggtgtc tctatctgta gtactatgac caatagacag tttcatcaaa 15240 aattactcaa gtcaatagcc gccactagag gagctactgt agtaattgga acaagcaaat 15300 tctatggtgg ttggcacaac atgctcaaaa ctgtttatag tgatgtagaa aaccctcacc 15360 ttatgggttg ggattatcct aaatgtgata gagccatgcc taacatgctt agaattatgg 15420 cctcacttgt tcttgctcgc aaacatacaa cgtgttgtag cttgtcacac cgtttctata 15480 gattagctaa tgagtgtgct caagtattga gtgaaatggt catgtgtggc ggttcactat 15540 atgttaaacc aggtggaacc tcatcaggag atgccacaac tgcttatgct aatagtgtgt 15600 ttaacatttg tcaagctgtc acggccaatg ttaatgcact tttatctact gatggtaaca 15660 aaattgccga taagtatgtc cgcaatttac aacacagact ttatgagtgt ctctatagaa 15720 atagagatgt tgacacagac tttgtgaatg agttttacgc atatttgcgt aaacatttct 15780 caatgatgat actctctgac gatgctgttg tgtgtttcaa tagcacttat gcatctcaag 15840 gtctagtggc tagcataaag aactttaagt cagttcttta ctatcaaaac aacgttttta 15900 tgtctgaagc aaaatgttgg actgagactg accttactaa aggacctcat gaattttgct 15960 ctcaacatac aatgctagtt aaacagggtg atgattatgt gtaccttcct tacccagatc 16020 catcaagaat cctaggtgcc ggttgttttg tagatgatat cgtaaaaaca gatggtacac 16080 ttatgattga acggttcgtg tctttagcta tagatgctta cccacttact aaacatccta 16140 atcaggagta tgctgatgtc tttcatttgt acttacaata catacgtaag ctacatgatg 16200 agttaacagg acacatgtta gacatgtatt ctgttatgct tactaatgat aacacttcaa 16260 ggtattggga acctgagttt tatgaggcta tgtacacacc gcatacagtc ttacaagctg 16320 ttggtgcttg tgttctttgc aattcacaga cttcattaag atgtggtgct tgcatacgta 16380 gaccattctt atgttgtaaa tgctgttacg accatgtcat ctcaacatca cataaattag 16440 tcttgtctgt taatccgtat gtttgcaatg ctccaggttg tgatgtcaca gatgtgactc 16500 aactttactt aggaggtatg agctattact gtaagtcaca taaaccaccc attagttttc 16560 cattgtgtgc taatggacaa gtttttggtc tctacaagaa tacatgtgtt ggtagcgata 16620 atgttactga ctttaatgca attgcaacat gtgactggac aaatgctggt gattacattt 16680 tagctaacac ctgtactgaa agactcaagc tttttgcagc agaaacgctc aaagctactg 16740 aggagacatt taaactgtct tatggtattg ctactgtacg tgaagtgctg tctgacagag 16800 aattacatct ttcatgggaa gttggtaaac ctagaccacc acttaaccga aattatgtct 16860 ttactggtta tcgtgtaact aaaaacagta aagtgcaaat cggagagtac acctttgaaa 16920 aaggtgacta tggtgatgct gttgtttacc gaggtacaac aacttacaaa ctcaacgttg 16980 gtgattattt tgtgctgaca tcacatacag taatgccatt aagtgcacct acactagtgc 17040 cacaagagca ctatgttaga attactggct tatacccaac actcaatatc tcagatgagt 17100 tttctagcaa tgttgcaaat tatcaaaagg ttggtatgca aaagtattct acactccagg 17160 gaccacctgg tactggtaaa agtcattttg ctattggtct agctctctac tacccttctg 17220 ctcgcatagt atatacagct tgctctcatg cagctgttga tgcactatgt gagaaggcat 17280 taaaatattt gcccatagac aaatgtagta gaattatacc tgcacgtgct cgtgtagagt 17340 gttttgataa attcaaggtg aattcaacat tagaacagta tgtcttttgt actgtaaatg 17400 cattgcctga gacgacagca gatatagttg tctttgatga aatttcaatg gccacaaatt 17460 atgatttgag tgttgtcaat gccagattac gtgctaagca ctatgtgtac attggtgatc 17520 ctgctcaatt acctgcacca cgcacattac taactaaggg tacactagaa ccagaatatt 17580 tcaattcagt gtgtagactt atgaaaacta taggtccaga catgttcctc ggaacttgtc 17640 gtagatgtcc tgctgaaatt gttgacactg tgagtgcttt ggtttatgat aataagctta 17700 aggcacataa agacaaatca gctcaatgct ttaaaatgtt ctacaagggt gttatcacgc 17760 atgatgtttc atctgcaatt aacaggccac aaataggcgt ggtaagagaa ttccttacac 17820 gtaaccctgc ttggagaaaa gctgtcttta tttcacctta caattcccag aatgctgtag 17880 cctcaaagat tttgggacta ccaactcaaa ctgttgattc atcacagggc tcagaatatg 17940 actatgtcat attcactcaa accactgaaa cagctcactc ttgtaatgta aacagattca 18000 acgttgctat taccagagca aaagtaggca tactttgcat aatgtctgat agagaccttt 18060 atgacaagtt gcaatttaca agtcttgaaa ttccacgtag gaatgtggca actttacaag 18120 ctgaaaatgt aacaggactc tttaaagatt gtagtaaggt aatcactggg ttacatccta 18180 cacaggcacc tacacactta agtgttgata ctaaattcaa aactgaaggt ttatgtgttg 18240 acatacctgg catacctaag gacatgacct atagaagatt aatctctatg atgggtttca 18300 aaatgaatta ccaggttaat ggttacccta acatgtttat cacccgcgaa gaagctataa 18360 gacatgtacg tgcatggatt ggcttcgatg tcgaaggttg tcatgctact agagaagctg 18420 ttggtaccaa tttaccttta cagctaggtt tttctacagg tgttaaccta gttgctgtac 18480 ctacaggtta tgttgataca cctaataata cagatttttc cagagttagt gctaaaccac 18540 cgcctggaga tcaatttaaa cacctcatac cacttatgta caaaggactt ccttggaatg 18600 tagtgcgtat aaagattgtc caaatgttaa gtgacacact taaaaatctc tctgacagag 18660 tcgtatttgt cttatgggca catggctttg agttgacatc tatgaagtat tttgtgaaga 18720 tcggacctga gcgcacatgt tgtctatgtg atagacgtgc tacatgcttt tccactgctt 18780 cagacactta tgcctgttgg catcattcta ttggatttga ttacgtctat aatccgttta 18840 tgattgatgt tcaacaatgg ggttttacag gtaacctaca aagcaaccat gatctgtatt 18900 gtcaagtcca tggtaatgca catgtagcta gttgtgatgc aatcatgact aggtgtctag 18960 ctgtccacga gtgctttgtt aagcgtgttg actggactat tgaatatcct ataatcggtg 19020 atgaactgaa gattaatgcg gcttgtagaa aggttcaaca catggttgtt aaagctgcat 19080 tattagcaga caaattccca gttcttcacg acattggtaa ccctaaagct attaagtgtg 19140 tacctcaagc tgatgtagaa tggaagttct atgatgcaca gccttgtagt gacaaagctt 19200 acaaaataga agaactgttc tattcttatg ccacacattc tgacaaattc acagatggtg 19260 tatgcctatt ttggaattgc aatgtcgata gatatcctgc taattccatt gtttgtagat 19320 ttgacactag agtgctatct aaccttaact tgcctggttg tgatggtggc agtttgtatg 19380 taaataagca tgcattccac acaccagctt ttgataaaag tgcttttgtt aatctaaagc 19440 aacttccatt tttctattac tctgacagtc catgtgagtc tcatggaaaa caagtagtgt 19500 cagatataga ttatgtacca ctaaagtctg ctacgtgtat aacacgttgc aatttaggtg 19560 gtgctgtctg tagacatcat gctaatgagt acagattgta tctcgatgct tataacatga 19620 tgatctcagc tggctttagc ttgtgggttt acaaacaatt tgatacctat aacctctgga 19680 acacttttac aagacttcag agtttagaaa atgtggcttt taatgttgta aataagggac 19740 actttgatgg acaacagggt gaagtaccag tttctatcat taacaacact gtttacacaa 19800 aagttgatgg tgttgatgta gaattgtttg agaacaaaac cacattacct gttaatgtag 19860 catttgagct ttgggctaag cgcaacatta aaccagtacc agaggtgaaa atactcaata 19920 atttgggtgt ggacattgct gctaatactg tgatctggga ctacaaaaga gatgctccag 19980 cacatatatc tactattggt gtttgttcta tgactgacat agccaagaaa ccaactgaaa 20040 cgatttgtgc accactcact gtcttttttg atggtagagt tgatggtcaa gtagacttat 20100 ttagaaatgc ccgtaatggt gttcttatta cagaaggtag tgttaaaggt ttacaaccat 20160 ctgtaggtcc caaacaagct agtcttaatg gagtcacatt aattggagaa gccgtaaaaa 20220 cacagttcaa ttattacaag aaagtggatg gtgttgtcca acaattacct gaaacttact 20280 ttactcagag tagaaactta caggaattta agcccaggag tcaaatggaa attgatttct 20340 tagaacttgc tatggatgaa ttcattgaac ggtataaatt agaaggctat gccttcgaac 20400 atatcgttta tggagatttt agtcatagtc agttaggtgg tttacatcta ctgattggac 20460 tagctaaacg ttttaaggaa tcaccttttg aacttgaaga ttttattcct atggacagta 20520 cagttaaaaa ctacttcata acagatgcgc aaacaggttc atctaagtgt gtgtgttctg 20580 ttattgatct tttacttgat gacttcgttg aaataataaa gtcccaagat ttatctgtag 20640 tttctaaggt tgtcaaagtg actattgact atacagaaat ctcatttatg ctttggtgta 20700 aagatggcca tgtagaaaca ttttacccaa aattacaatc tagtcaagcg tggcaaccgg 20760 gtgttgctat gcctaatctt tacaaaatgc aaagaatgct attagaaaag tgtgaccttc 20820 aaaattatgg tgatagtgca acattaccta aaggcataat gatgaatgtc gcaaaatata 20880 ctcaactgtg tcaatattta aacacactga cattagctgt accctataat atgagagtta 20940 tccattttgg tgctggttct gataaaggag ttgcaccagg tacagctgtt ttaagacaat 21000 ggttgcctac aggtacgctg cttgtcgatt cagatcttaa tgactttgtc tctgatgcag 21060 attcaacttt gattggtgat tgtgcaactg tacatacagc taataaatgg gatctcatta 21120 ttagtgatat gtacgaccct aagactaaga atgtcacaaa agaaaacgac tctaaagagg 21180 gttttttcac ttacatttgt gggtttatac aacaaaagct agctcttgga ggttccgtgg 21240 ctataaagat aacagaacat tcttggaatg ctgatcttta taagctcatg ggacacttcg 21300 catggtggac agcctttgtt actaatgtga atgcgtcatc atctgaagca tttttaatcg 21360 gatgtaacta ccttggcaaa ccacgcgaac aaatagatgg ttatgtcatg catgcaaatt 21420 acatattttg gaggaataca aatccaattc agctttcttc ttattcttta ttcgacatga 21480 gtaaattccc ccttaaatta aggggtactg ctgttatgtc tttaaaagaa ggtcaaatca 21540 atgatatgat tctctctctt cttagtaaag gtagacttat aattagagaa aacaacagag 21600 ttgttatttc tagtgatgtt cttgttaaca actaaacgaa caatgtttgt ttttcttgtt 21660 ttattgccac tagtctctag tcagtgtgtt aatcttacaa ccagaactca attaccccct 21720 gcatacacta attctttcac acgtggtgtt tattaccctg acaaagtttt cagatcctca 21780 gttttacatt caactcagga cttgttctta cctttctttt ccaatgttac ttggttccat 21840 gctatacatg tctctgggac caatggtact aagaggtttg ataaccctgt cctaccattt 21900 aatgatggtg tttactttgc ttccactgag aagtctaaca taataagagg ctggattttt 21960 ggtactactt tagattcgaa aacccagtcc ctacttattg ttaataacgc tactaatgtt 22020 gttatcaaag tctgtgaatt tcaattttgt aacgatccat ttttgggtgt ttattaccac 22080 aaaaacaaca aaagttggat ggaaagtgag ttcagagttt attctagtgc gaataattgc 22140 acttttgaat acgtctctca gccttttctt atggaccttg aaggaaaaca gggtaatttc 22200 aaaaatctta gggaatttgt gttcaagaat attgatggtt acttcaagat atactctaag 22260 cacacgccta ttaatttagt gcgtgatctc cctcagggtt tttcggcttt agaaccattg 22320 gtagatttgc caataggtat taacatcact aggtttcaaa ctttacttgc tttacataga 22380 agttatttaa ctcctggtga ttcttcttca ggttggacag ctggtgctgc agcttattat 22440 gtgggttatc ttcaacctag gacttttcta ctgaagtaca atgaaaatgg aaccattaca 22500 gatgctgtag actgtgcact tgaccctctc tcagaaacaa agtgtacgtt gaaatccttc 22560 actgtagaaa aaggaatcta tcaaacttct aactttagag tccaaccaac agaatctatt 22620 gttagatttc ctaacatcac aaacttgtgc ccttttggtg aagtttttaa cgccaccaga 22680 tttgcatctg tttatgcttg gaacaggaag agaatcagca actgtgttgc tgattattct 22740 gtcctgtata attccgcatc attttccact tttaagtgtt atggagtgtc tcctactaaa 22800 ttaaatgatc tctgctttac taatgtctat gcagattcat ttgtaattag aggtgatgaa 22860 gtcagacaaa tcgctccagg gcaaactgga aagattgctg attataacta caaattacca 22920 gatgatttta caggctgcgt tatagcttgg aattctaaca atcttgattc taaggttggt 22980 ggtaattata attacctgta cagattgttt aggaagtcta atctcaaacc ttttgagaga 23040 gatatttcaa ctgaaatcta tcaggccggt agcacacctt gtaatggtgt tgaaggtttt 23100 aattgttact ttcctctgca atcatatggt ttccaaccca ctaatggtgt tggttaccaa 23160 ccatacagag tagtagtact ttcttttgaa cttctacatg caccagcaac tgtttgtgga 23220 cctaaaaagt ctactaattt ggttaagaac aagtgtgtca atttcaactt caatggttta 23280 acaggcacag gtgttcttac tgagtctaac aaaaagtttc tgcctttcca acaatttggc 23340 agagacattg ctgacactac tgatgctgtt cgtgatccac aaacacttga gattcttgac 23400 attacaccat gttcttttgg tggtgtcagt gttataacac caggaacaaa tacttctaac 23460 caggttgctg ttctttatca ggatgttaac tgcacagaag tccctgttgc tattcatgca 23520 gatcaactta ctcctacttg gcgtgtttat tctacaggtt ctaatgtttt tcaaacacgt 23580 gcaggctgtt taataggggc tgaacatgtc aacaactcat atgagtgtga catacccatt 23640 ggtgcaggta tatgcgctag ttatcagact cagactaatt ctcctcggag agcaagaagt 23700 gtagctagtc aatccatcat tgcctacact atgtcacttg gtgcagaaaa ttcagttgct 23760 tactctaata actctattgc catacccaca aattttacta ttagcgttac cacagaaatt 23820 ctaccagtgt ctatgaccaa gacatcagta gattgtacaa tgtacatttg tggtgattca 23880 actgaatgca gcaatctttt gttgcaatat ggcagttttt gtacacaatt aaaccgtgct 23940 ttaactggaa tagctgttga acaagacaaa aacacccaag aagtttttgc acaagtcaaa 24000 caaatttaca agacaccacc aattaaagat tttggcggtt ttaattttag ccagatactg 24060 ccagatccat caaaaccaag caagaggtca tttattgaag atctactgtt caacaaagtg 24120 acacttgcag atgctggctt catcaaacaa tatggtgatt gccttggtga tattgctgct 24180 agagacctca tttgtgcaca aaagtttaac ggccttactg ttttgccacc tttgctcaca 24240 gatgaaatga ttgctcaata cacttctgca ctgttagcag gtacaatcac ttctggttgg 24300 acttttggtg caggtgctgc attacaaata ccatttgcta tgcaaatggc ttataggttt 24360 aatggtattg gagttacaca gaatgttctc tatgagaacc aaaaattgat tgccaaccaa 24420 tttaatagtg ctattggcaa aattcaagac tcactttctt ccacagcaag tgcacttgga 24480 aaacttcaag atgtggtcaa ccaaaatgca caagctttaa acacgcttgt taaacaactt 24540 agctccaatt ttggtgcaat ttcaagtgtt ttaaacgaca tcctttcacg tcttgacaaa 24600 gttgaggctg aagtgcaaat tgataggttg atcacaggca gacttcaaag tttgcagaca 24660 tatgtgactc aacaattaat tagagctgca gaaatcagag cttctgctaa tcttgctgct 24720 actaaaatgt cagagtgtgt acttggacaa tcaaaaagag ttgacttttg cggaaagggc 24780 tatcatctta tgtcatttcc tcagtcagca cctcatggtg tcgtcttttt gcatgtgact 24840 tatgtccctg cacaagaaaa gaacttcaca actgctcctg ccatttgtca tgatggaaaa 24900 gcacactttc ctcgtgaagg tgtctttgtt tcaaatggca cacactggtt tgtaacacaa 24960 aggaattttt atgaaccaca aatcattact acagacaaca catttgtgtc tggtaactgt 25020 gatgttgtaa taggaattgt caacaacaca gtttatgatc ctttgcaacc tgaattagac 25080 tcattcaagg aggagcttga taaatacttc aagaaccata cctcaccaga tgttgattta 25140 ggtgacatct ctggcattaa tgcttcagtt gtaaacattc agaaagaaat cgaccgcctc 25200 aatgaggttg ccaagaattt aaatgaatct ctcatcgatc tccaagaact tggaaagtat 25260 gagcagtata taaaatggcc atggtacatt tggctaggtt ttatagctgg cttgattgcc 25320 atagtaatgg tgacaattat gctttgctgt atgaccagtt gctgtagttg tctcaagggc 25380 tgttgttctt gtggatcctg ctgcaaattt gacgaggacg actctgagcc agtgctcaaa 25440 ggagtcaaat tacattacac ataaacgaac ttatggattt gtttatgaga atcttcacaa 25500 ttggaactgt aactttgaag caaggtgaaa tcaaggatgc tactccttca gattttgtta 25560 gagctactgc aacgataccg atacaagcat cacttccttt cggatggctt attgttggcg 25620 ttgcacttct tgctgttttt cagagcgctt ccaaaatcat aaccctcaaa aagagatggc 25680 aactagcact ctccaagggt gttcactttg tttgcaactt gctgttgttg tttgtaacag 25740 tttactcaca tcttttgctt gttgctgctg gccttgaagc cccttttctc tatctttatg 25800 ctttagtcta cttcttgcag agtataaact ttgtacgcat aataatgagg ctttggcttt 25860 gctggaaatg ccgttccaaa aacccattac tttatgatgc caactatttt ctttgctggc 25920 atactaattg ttacgactat tgtatacctt acaatagtgt aacttcttca attgtcatta 25980 cttcaggtga tggcacaaca agtcctattt ctgaacatga ctaccagatt ggtggttata 26040 ctgaaaaatg ggaatctgga gtaaaagact gtgttgtatt acacagttac ttcacttcag 26100 actattacca gctgtactca actcaattga gtacagacac tggtgttgaa catgttacct 26160 tcttcatcta caataaaatc gttgatgagc ctgaagaaca tgtccaaatt cacacaatcg 26220 acgtttcatc cggagttgtt aatccagtaa tggaaccaat ttatgatgaa ccgacgacga 26280 ctactagcgt gcctttgtaa gcacaagctg atgagtacga acttatggca gattccaacg 26340 gtactattac cgttgaggag ctgaaaaagc tccttgaaca atggaaccta gtaataggtt 26400 tcctattcct tacatggatt tgcctgctgc aatttgccta tgccaacagg aataggtttt 26460 tgtacatcat taagttgatt ttcctctggc tgttatggcc agtaacttta gcttgttttg 26520 tgcttgctgc tgtttacaga ataaattgga tcaccggtgg aattgctatt gcaatggctt 26580 gtcttgtagg attgatgtgg ctaagctact tcattgcttc tttcagactg tttgcgcgta 26640 cgcgttccat gtggtcattc aatccagaaa ctaacattct tctcaacgtg ccactccatg 26700 gaactattct gactagaccg cttctagaaa gtgaactcgt aatcggagct gttatccttc 26760 gtggacatct tcgtattgct ggacatcatc taggacgctg tgacatcaag gatctaccta 26820 aagaaatcac tgttgctaca tcacgaacgc tttcttatta caaattggga gcttcacagc 26880 gtgtagcagg tgattcaggt tttgctgcat atagtcgcta caggattggc aactataaat 26940 taaacacaga ccattccagt agcagtgaca atattgcttt gcttgtacag taagtgacaa 27000 cagatgtttc atctcgttga ctttcaggtt actatagcag agatattact aatcatcatg 27060 aggactttta aagtttccat ttggaatctt gattacatca taaacctcat aattaagaac 27120 ttaagcaagt cactaactga gaataaatat tctcaactag acgaggagca gccaatggag 27180 attgattaaa cgaacatgaa aattattctt ttcttggcac tgataacact cgctacttgt 27240 gagctttatc actaccaaga gtgtgttaga ggtacaacag tacttttaaa agaaccttgc 27300 tcgtcgggaa catacgaggg caattcacca tttcatcctc tagctgataa caaatttgca 27360 ctgacttgct ttagcactca atttgctttt gcttgtcctg acggcgtaaa acacgtctat 27420 cagttacgtg ccagatcagt ttcacctaaa ctgttcatca gacaagagga agttcaagaa 27480 ctttactctc caatttttct tattgttgcg gcaatagtgt ttataacact ttgcttcaca 27540 ctcaaaagaa agacagaatg attgaacttt cattaattga cttctatttg tgctttttag 27600 cctttctgct attccttgtt ttaattatgc ttattatctt ttggttctca cttgaactgc 27660 aagatcataa tgaaacttgt cacgcctaag acgttcgtgt tgttttagat ttcatctaaa 27720 cgaacaaact aaaatgtctg ataatggacc tcaaaatcag cgaaatgcac ctcgcattac 27780 gtttggtgga ccatcagatt caactggcag taaccagaat ggagaacgaa gtggtgcgcg 27840 atcaaaacaa cgccgcccgc aaggtttacc caataatact gcgtcttggt tcaccgctct 27900 cactcaacat ggcaaggaag atttaaaatt ccctcgagga caaggcgttc caattaacac 27960 caatagcagt ccagatgacc aaattggcta ctaccgccgc gccacaagac gaattcgtgg 28020 tggtgatggt aaaatgaaag atctcagtcc aagatggtat ttctactatc taggaactgg 28080 gccagaagct ggacttcctt atggtgctaa caaagatggc atcatatggg ttgcaactga 28140 gggagccttg aatacaccaa aagatcacat tggcaccaga aatcctgcta acaatgctgc 28200 aatcgtgcta caacttcctc aaggaacaac attaccaaaa ggtttttacg cagaagggtc 28260 tagaggtgga agtcaagcct cttctagatc atcatcacgt agtcgcaaca gttcaagaaa 28320 ttcaactcca ggttcaagta gaggaacttc tcctgctaga atggctggaa atggaggtga 28380 tgctgctctt gctttgttac tacttgacag attgaaccag cttgagagca aaatgtctgg 28440 taaaggccaa caacaacaag gccaaactgt cactaagaaa tctgctgctg aggcttctaa 28500 gaagcctaga caaaaacgta ctgccactaa agcatacaat gtaacacaag ctttcggcag 28560 acgtggtcca gaacaaactc aaggaaattt tggggatcag gaactaatca gacaaggaac 28620 tgattacaaa cattggccgc aaattgcaca atttgctcct tctgcttcag cgttctttgg 28680 aatgtcgaga attggaatgg aagtcacacc ttcgggaaca tggttgacct atacaggtgc 28740 catcaaattg gatgacaaag atccaaattt caaagatcaa gtcattttgc tgaataagca 28800 tattgacgca tacaaaacat tcccaccaac agagcctaaa aaggacaaaa agaagaaggc 28860 tgatgaaact caagccttac cgcagagaca gaagaaacag caaactgtga ctcttcttcc 28920 tgctgcagat ttggatgatt tctccaaaca attgcaacaa tccatgagca gtgctgactc 28980 aactcaggcc taaactcatg cagaccacac aaggcagatg ggctatataa acgttttcgc 29040 ttttccgttt acgatatata gtctactctt gtgcagaatg aattctcgta actacatagc 29100 acaagtagat gtagttaact ttaatctcac atagcaatct ttaatcagtg tgtaacatta 29160 gggaggactt gaaagagcca ccacattttc accgaggcca cgcggagtac gatcgagtgt 29220 acagtgaaca atgctaggga gagctgccta tatggaagag ccctaatgtg taaaattaat 29280 tttagtagtg ctatccccat gtgattttaa tagcttctta ggagaatgac aaaaaaaaac 29340 aaaaaaaa 29348 <210> 43 <211> 29152 <212> DNA <213> Artificial Sequence <220> <223> Synthesis optimized sequence E-protein ORF6, and ORF8 triple deletion <400> 43 caaatataac gaaaggctca gtcgaaagac tgggcctttc gttttatctg ttgtttgtcg 60 taatacgact cactataggg attaaaggtt tataccttcc caggtaacaa accaaccaac 120 tttcgatctc ttgtagatct gttctctaaa cgaactttaa aatctgtgtg gctgtcactc 180 ggctgcatgc ttagtgcact cacgcagtat aattaataac taattactgt cgttgacagg 240 acacgagtaa ctcgtctatc ttctgcaggc tgcttacggt ttcgtccgtg ttgcagccga 300 tcatcagcac atctaggttt cgtccgggtg tgaccgaaag gtaagatgga gagccttgtc 360 cctggtttca acgagaaaac acacgtccaa ctcagtttgc ctgttttaca ggttcgcgac 420 gtgttagtac gtggttttgg agattcagtg gaagaagtct tatcagaggc acgtcaacat 480 cttaaagatg gcacttgtgg cttagtagaa gttgaaaaag gcgttttgcc tcaacttgaa 540 cagccctatg tgttcatcaa acgttctgat gctagaactg cacctcatgg tcatgttatg 600 gttgagctgg tagcagaatt agaaggtatt cagtacggtc gtagtggtga gacattaggt 660 gttttagttc ctcatgtggg cgaaatacca gtggcttacc gcaaagttct tcttagaaag 720 aacggtaata aaggagctgg tggccatagt tacggcgctg atttaaagtc atttgactta 780 ggcgacgagc ttggcactga tccttatgaa gatttccaag aaaactggaa cactaaacat 840 agcagtggtg ttacccgtga actcatgcgt gagttaaatg gaggtgcata cactcgctat 900 gtcgataaca acttctgtgg acctgatggt taccctcttg agtgcattaa agaccttcta 960 gcacgtgctg gtaaagcttc atgcactttg tccgaacaac tggactttat tgacactaag 1020 aggggtgtat actgctgccg tgaacatgag catgaaattg cttggtacac ggaacgttct 1080 gaaaagagct atgaattgca gacacctttt gaaattaaac tggcaaagaa atttgacacc 1140 ttcaatgggg aatgtccaaa ttttgtattt cccctcaatt ccataatcaa gactattcaa 1200 ccaagggttg aaaagaaaaa gcttgatggc tttatgggta gaattcgatc tgtctatcca 1260 gttgcgtcac caaatgaatg caaccaaatg tgcctttcaa ctctcatgaa gtgtgatcat 1320 tgtggtgaaa cttcatggca gacgggcgat tttgttaaag ccacttgcga attttgtggc 1380 actgagaatt tgactaaaga aggtgccact acttgtggtt acttacccca aaatgctgtt 1440 gttaaaattt actgtccagc atgtcacaat tcagaagtag gacctgagca tagtcttgcc 1500 gaataccata atgaatctgg cttgaaaacc attcttcgta agggtggtcg cactattgct 1560 tttggaggat gtgtgttctc ttatgttggt tgccataaca agtgtgctta ttgggttcca 1620 cgtgcttcag ctaacatagg ttgtaaccat acaggtgttg ttggagaagg ttccgaaggt 1680 cttaatgaca accttcttga aatactccaa aaagagaaag tcaacatcaa tattgttggt 1740 gactttaaac ttaatgaaga gatcgccatt attttggcat ctttttctgc ttccacaagt 1800 gcttttgtgg aaactgtgaa aggtttggat tataaagcat tcaaacagat tgttgaatcc 1860 tgtggtaatt ttaaggttac aaagggaaaa gctaaaaaag gtgcctggaa tattggtgaa 1920 cagaaatcaa tactgagtcc tctttatgca tttgcatcag aggctgctcg tgttgtacga 1980 tcaattttct cccgcactct tgaaactgct caaaattctg tgcgtgtttt acagaaggcc 2040 gctataacaa tactagatgg aatttcacag tattcactga gactcattga tgctatgatg 2100 ttcacatctg atttggctac taacaatcta gttgtaatgg cctacattac aggtggtgtt 2160 gttcagttga cttcgcagtg gctaactaac atctttggca ctgtttatga aaaactcaaa 2220 cccgtccttg attggcttga agagaagttt aaggaaggtg tagagtttct tagagacggt 2280 tgggagattg ttaaattcat ctcaacctgt gcttgtgaaa ttgtcggtgg acaaattgtc 2340 acctgtgcta aggaaattaa ggagagtgtt cagacattct ttaagcttgt aaacaagttt 2400 ttggctttgt gtgctgactc tatcattatt ggtggagcta aacttaaagc cttgaattta 2460 ggtgaaacat ttgtcacgca ctcaaaggga ttgtacagaa agtgtgttaa atccagagaa 2520 gaaactggcc tactcatgcc tctaaaagcc ccaaaagaaa ttatcttctt agagggagaa 2580 acacttccca cagaagtgtt aacagaggaa gttgtcttga aaactggtga tttacaacca 2640 ttagaacaac ctactagtga agctgttgaa gctccattgg ttggtacacc agtttgtatt 2700 aacgggctta tgttgctcga aatcaaagac acagaaaagt actgtgccct tgcacctaat 2760 atgatggtaa caaacaatac cttcacactc aaaggcggtg caccaacaaa ggttactttt 2820 ggtgatgaca ctgtgataga agtgcaaggt tacaagagtg tgaatatcac ttttgaactt 2880 gatgaaagga ttgataaagt acttaatgag aagtgctctg cctatacagt tgaactcggt 2940 acagaagtaa atgagttcgc ctgtgttgtg gcagatgctg tcataaaaac tttgcaacca 3000 gtatctgaat tacttacacc actgggcatt gatttagatg agtggagtat ggctacatac 3060 tacttatttg atgagtctgg tgagtttaaa ttggcttcac atatgtattg ttctttctac 3120 cctccagatg aggatgaaga agaaggtgat tgtgaagaag aagagtttga gccatcaact 3180 caatatgagt atggtactga agatgattac caaggtaaac ctttggaatt tggtgccact 3240 tctgctgctt tacaacctga agaagaacaa gaagaagatt ggttagatga tgatagtcaa 3300 caaactgttg gtcaacaaga cggcagtgag gacaatcaga caactactat tcaaacaatt 3360 gttgaggttc aacctcaatt agagatggaa cttacaccag ttgttcagac tattgaagtg 3420 aatagtttta gtggttatct taaacttact gacaatgtat acatcaagaa tgcagacatt 3480 gtggaagaag ctaaaaaggt aaaaccaaca gtggttgtta atgcagccaa tgtttacctt 3540 aaacatggag gaggtgttgc aggagcctta aataaggcta ctaacaatgc catgcaagtt 3600 gaatctgatg attacatagc tactaatgga ccacttaaag tgggtggtag ttgtgtttta 3660 agcggacaca atcttgctaa acactgttta catgttgtcg gcccaaatgt taacaaaggt 3720 gaagatattc aacttcttaa gagtgcttat gaaaatttta accagcacga agttctactt 3780 gcaccattat tatcagctgg tatttttggt gctgacccta tacattcttt aagagtttgt 3840 gtagatactg ttcgcacaaa tgtctactta gctgtctttg ataaaaatct ctatgacaaa 3900 cttgtttcaa gctttttgga aatgaagagt gaaaagcaag ttgaacaaaa gatcgctgag 3960 attcctaaag aggaagttaa gccatttata actgaaagta aaccttcagt tgaacagaga 4020 aaacaagatg ataagaagat caaagcttgt gttgaagaag ttacaacaac tctggaagaa 4080 actaagttcc tcacagaaaa cttgctcctt tatatcgaca ttaatggcaa tcttcatcca 4140 gattctgcca ctcttgttag tgacattgac atcactttct taaagaaaga tgctccatat 4200 atagtgggtg atgttgttca agagggtgtt ttaactgctg tggttatacc tactaaaaag 4260 gctggtggca ctactgaaat gctagcgaaa gctttgagaa aagtgccaac agacaattat 4320 ataaccactt acccgggtca gggtttaaat ggttacactg tagaggaggc aaagacagtg 4380 cttaaaaagt gtaaaagtgc cttttacatt ctaccatcta ttatctctaa tgagaagcaa 4440 gaaattcttg gaactgtttc ttggaatttg cgagaaatgc ttgcacatgc agaagaaaca 4500 cgcaaattaa tgcctgtctg tgtggaaact aaagccatag tttcaactat acagcgtaaa 4560 tataagggta tcaagataca agagggtgtg gttgattatg gtgctagatt ttacttttac 4620 accagtaaaa caactgtagc gtcacttatc aacacactta acgatctaaa tgaaactctt 4680 gttacaatgc cacttggcta tgtaacacat ggcttaaatt tggaagaagc tgctcggtat 4740 atgagatctc tcaaagtgcc agctacagtt tctgtttctt cacctgatgc tgttacagcg 4800 tataatggtt atcttacttc ttcttctaaa acacctgaag aacattttat tgaaaccatc 4860 tcacttgctg gttcctataa agattggtcc tattctggac aatctacaca actaggtata 4920 gaatttctta agagaggtga taaaagtgta tattacacgt ccaatcctac cacattccac 4980 ctagatggtg aagttatcac ctttgacaat cttaagacac ttctttcttt gagagaagtg 5040 aggactatta aggtgtttac aacagtagac aacattaacc tccacacgca agttgtggac 5100 atgtcaatga catatggaca acagtttggt ccaacttatt tggatggagc tgatgttact 5160 aagataaaac ctcataactc acatgaaggt aaaacatttt acgttttgcc taatgatgac 5220 actctacgtg ttgaggcttt tgagtactac cacacaactg atcctagttt tctgggtagg 5280 tacatgtcag cattaaatca cactaaaaag tggaaatacc cacaagttaa tggtttaact 5340 tcgattaaat gggcagataa caactgttat cttgccactg cattgttaac actccaacaa 5400 atagagttga agtttaatcc acctgctcta caagatgctt attacagagc aagggctggt 5460 gaagctgcta acttttgtgc acttatctta gcctactgta ataagacagt aggtgagtta 5520 ggtgatgtta gagaaacaat gagttacttg tttcaacatg ccaatttaga ttcttgcaaa 5580 agagtcttga acgtggtgtg taaaacttgt ggacaacagc agacaaccct taagggtgta 5640 gaagctgtta tgtacatggg cacactttct tatgaacaat tcaagaaagg tgttcagata 5700 ccttgtacgt gtggtaaaca agctacaaaa tatctagtac aacaggagtc accttttgtt 5760 atgatgtcag caccacctgc tcagtatgaa cttaagcatg gtacatttac ttgtgctagt 5820 gagtacactg gtaattacca gtgtggtcac tataagcata taacttctaa ggaaactttg 5880 tattgcatag acggtgcttt acttacaaag tcctcagaat acaaaggtcc tattacggat 5940 gttttctaca aagaaaacag ttacacaaca accataaaac cagttactta taagttggat 6000 ggtgttgttt gtacagaaat tgaccctaag ttggacaatt attataagaa ggacaactct 6060 tatttcacag agcaaccaat tgatcttgta ccaaaccaac catatccaaa cgcaagcttc 6120 gataatttta agttcgtatg cgataatatc aaatttgctg atgatctcaa ccagttaact 6180 ggttataaga aacctgcttc aagagagctt aaagttacat ttttccctga cttaaatggt 6240 gatgtggtgg ctattgatta taaacactac acaccctctt ttaagaaagg agctaaattg 6300 ttacataagc ctattgtttg gcatgttaac aatgcaacta ataaagccac gtataaacca 6360 aatacctggt gtatacgttg tctttggagc acaaaaccag ttgaaacatc aaattcgttt 6420 gatgtactga agtcagagga cgcgcaggga atggataatc ttgcatgtga agatctaaaa 6480 ccagtctctg aagaagtagt ggaaaatcct accatacaga aagacgttct tgagtgtaat 6540 gtgaaaacta ccgaagttgt aggagacatt atacttaaac cagcaaataa tagtttgaag 6600 atcacagaag aggttggcca cacagatcta atggctgctt atgtagacaa ttctagtctt 6660 actattaaga aacctaatga actctctaga gtattaggtt tgaaaaccct tgctactcat 6720 ggtttagctg ctgttaatag tgtcccttgg gatactatag ctaattatgc taagcctttt 6780 cttaacaaag ttgttagtac aactactaac atagttacac ggtgtcttaa tcgtgtttgt 6840 actaattata tgccttactt ctttacttta ttgctacaat tgtgtacttt tactagaagt 6900 acaaattcta gaatcaaggc atctatgccg actactatag caaagaatac tgttaagagt 6960 gtcggtaaat tttgtctaga ggcttcattt aattatctca agtcacctaa cttttctaag 7020 ctgataaaca ttatcatctg gtttttgcta ttaagtgttt gcctaggttc tttaatctac 7080 tcaaccgctg ctttaggtgt tttaatgtct aatttaggca tgccttctta ctgtactggt 7140 tacagagaag gctatttgaa ctctactaat gtcactattg caacctactg tactggatct 7200 ataccttgta gtgtttgtct tagtggttta gattctttag acacctatcc ttctcttgaa 7260 actatacaga ttaccatttc atctttcaaa tgggatttaa ctgcttttgg cttagttgca 7320 gagtggtttt tggcatatat tcttttcact aggtttttct atgtacttgg attggctgca 7380 atcatgcaat tgtttttcag ctattttgca gtccatttta ttagtaactc ttggcttatg 7440 tggcttataa ttaatcttgt gcagatggcc ccgatttcag ctatggttag aatgtacatc 7500 ttctttgcct cattttatta tgtgtggaaa agttatgtgc atgttgtaga cggttgtaat 7560 tcatcaactt gtatgatgtg ttacaaacgt aatagagcaa caagagtcga atgtacaact 7620 attgttaatg gtgttagaag gtccttttat gtctatgcta atggaggtaa aggcttttgc 7680 aaactacaca attggaattg tgttaattgt gatacattct gtgctggtag tacatttatt 7740 agtgatgaag ttgcgagaga cttgtcacta cagtttaaaa gaccaataaa tcctactgac 7800 caatcttctt acatcgttga tagtgttaca gtgaagaatg gttccatcca tctttacttt 7860 gataaagctg gtcaaaagac ttatgaaaga cattctctct ctcattttgt taacttagac 7920 aacctgagag ctaataacac taaaggttca ttgcctatta atgttatcgt tttcgacggt 7980 aaatcaaaat gtgaagaatc atctgcaaaa tcagcgtctg tttactacag tcagcttatg 8040 tgtcaaccta tactgttact agatcaggca ttagtgtctg atgttggtga tagtgcggaa 8100 gttgcagtta aaatgtttga tgcttacgtt aatacgtttt catcaacttt taacgtacca 8160 atggaaaaac tcaaaacact agttgcaact gcagaagctg aacttgcaaa gaatgtgtcc 8220 ttagacaatg tcttatctac gtttatttca gcagctcggc aagggtttgt tgattcagat 8280 gtagaaacta aagatgttgt tgaatgtctt aaattgtcac atcaatctga catagaagtt 8340 actggcgata gttgtaataa ctatatgctc acctataaca aagttgaaaa catgacaccc 8400 cgtgaccttg gtgcttgtat tgactgtagt gctagacata ttaatgcgca ggtagcaaaa 8460 agtcacaaca ttgctttgat atggaacgtt aaagatttca tgtcattgtc tgaacaacta 8520 cgaaaacaaa tacgtagtgc tgctaaaaag aataacttac ccttcaagtt gacatgtgca 8580 actactagac aagttgttaa tgttgtaaca acaaagatag cacttaaggg tggtaaaatt 8640 gtgaataact ggttgaagca gcttattaaa gttacacttg tgttcctttt tgttgctgct 8700 attttctatc tgataacacc tgttcatgtc atgtctaaac atactgactt ttcaagtgaa 8760 atcataggat acaaggctat tgatggtggt gtcactcgtg acatagcatc tacagatact 8820 tgttttgcta acaaacatgc tgattttgac acatggttta gccagcgtgg tggtagttat 8880 actaatgaca aagcttgccc attgattgct gcagtcataa caagagaagt gggttttgtc 8940 gttcctggtt tgcctggaac gatattacgc acaactaatg gtgacttttt gcatttctta 9000 cctagagttt ttagtgcagt tggtaacatc tgttacacac catcaaaact tatagagtac 9060 actgactttg caacatcagc ttgtgttttg gctgctgaat gtacaatttt taaagacgct 9120 tctggtaagc cagtaccata ttgttatgat accaatgtac tagaaggttc tgttgcttat 9180 gaaagtttac gccctgacac acgttatgtg ctcatggatg gctctattat tcaatttcct 9240 aacacctacc ttgaaggttc tgtaagagtg gtaacaactt ttgattctga gtactgtagg 9300 cacggcactt gtgaaagatc agaagctggt gtttgtgtat ctactagtgg tagatgggta 9360 cttaacaacg attattacag atctttacca ggagttttct gtggtgtaga tgctgtaaat 9420 ttgcttacta acatgtttac accactaatt caacctattg gtgctttgga catatcagca 9480 tctatagtag ctggtggtat tgtagctatc gtagtaacat gccttgccta ctattttatg 9540 aggtttagac gtgcttttgg tgaatacagt catgtagttg cctttaatac tctcctattc 9600 cttatgtcat tcactgtact ctgtttaaca ccagtttact cattcttacc tggtgtttat 9660 tctgttattt acctgtactt gacattttat ctgactaatg atgtttcttt tctcgcacat 9720 attcagtgga tggttatgtt cacaccttta gtacctttct ggataacaat tgcttacatc 9780 atttgtattt ccacaaagca tttctattgg ttctttagta attacctaaa gagacgtgta 9840 gtctttaatg gtgtttcctt tagtactttt gaagaagctg cgctgtgcac ctttttgtta 9900 aataaggaga tgtatctaaa gttgcgtagt gatgtgctat tacctcttac gcaatataat 9960 agatacttag ctctttataa caagtacaag tatttcagtg gagcaatgga tacaactagc 10020 tacagagaag ctgcttgttg tcatctcgca aaggctctca atgacttcag taactcaggt 10080 tctgatgttc tttaccaacc accacaaacc tctatcacct cagctgtttt gcagagtggt 10140 tttagaaaaa tggcattccc atctggtaaa gttgagggtt gtatggtaca agtaacttgt 10200 ggtacaacta cacttaacgg tctttggctt gatgacgtag tttactgtcc aagacatgtg 10260 atctgcacct ctgaagatat gcttaaccct aattatgaag atctactcat ccgtaagtct 10320 aatcataact tcttggtaca ggctggtaat gttcaactca gggttattgg acattctatg 10380 caaaattgtg tacttaagct taaggttgat acagccaatc ctaagacacc taagtataag 10440 tttgttcgca ttcaaccagg acagactttt tcagtgttag cttgttacaa tggttcacca 10500 tctggtgttt accaatgtgc tatgaggccc aatttcacta ttaagggttc attccttaat 10560 ggttcatgtg gtagtgttgg ttttaacata gattatgact gtgtctcttt ttgttacatg 10620 caccatatgg aattaccaac tggagttcat gctggcacag acttagaagg taacttttat 10680 ggaccttttg ttgacaggca aacagcacaa gcagctggta cagatacaac tattacagtt 10740 aatgttcttg cttggttgta cgctgctgtt ataaatggag acaggtggtt tctcaatcga 10800 tttaccacaa ctcttaatga ctttaacctt gtggctatga agtacaatta tgaacctcta 10860 acacaagacc atgttgacat actaggacct ctttctgctc aaactggaat tgccgtttta 10920 gatatgtgtg cttcattaaa agaacttctg caaaatggta tgaatggacg taccatattg 10980 ggtagtgctt tattagaaga tgagtttaca ccttttgatg ttgttagaca atgctcaggt 11040 gttactttcc aaagtgcagt gaaaagaaca atcaagggta cacaccactg gttgttactc 11100 acaattttga cttcactttt agttttagtc cagagtactc aatggtcttt gttctttttc 11160 ttctacgaaa atgccttttt accttttgct atgggtatta ttgctatgtc tgcttttgca 11220 atgatgtttg tcaaacataa gcatgcattt ctctgtttgt ttttgttacc ttctcttgcc 11280 actgtagctt actttaatat ggtctacatg cctgctagtt gggtgatgcg tattatgaca 11340 tggttggata tggttgatac tagtttgtct ggttttaagc taaaagactg tgttatgtat 11400 gcatcagctg tagtgttact aatccttatg acagcaagaa ctgtgtatga tgatggtgct 11460 aggagagtgt ggacacttat gaatgtcttg acactcgttt ataaagttta ctatggcaac 11520 gctttagatc aagccatttc catgtgggct cttataatct ctgttacttc taactactca 11580 ggtgtagtta caactgtcat gtttttggcc agaggtattg tttttatgtg tgttgagtat 11640 tgccctattt tcttcataac tggtaataca cttcagtgta taatgctagt ctattgtttc 11700 ttaggctatt tttgtacttg ttacttcggc ctcttttgtt tactcaaccg ctactttaga 11760 ctgactcttg gtgtttatga ttacttagtg tctacacagg agtttagata tatgaattca 11820 cagggactac tcccacccaa gaatagcata gatgccttca aactcaacat taaattgttg 11880 ggtgttggtg gcaaaccttg tatcaaagta gccactgtac agtctaaaat gtcagatgta 11940 aagtgcacat cagtagtctt actctcagtt ttgcaacaac tcagagtaga atcatcatct 12000 aaattgtggg ctcaatgtgt ccagttacac aatgacattc tcttagctaa agatactact 12060 gaagcctttg aaaaaatggt ttcactactt tctgttttgc tttccatgca gggtgctgta 12120 gacataaaca agctttgtga agaaatgctg gacaacaggg caaccttaca agctatagcc 12180 tcagagttta gttcccttcc atcatatgca gcttttgcta ctgctcaaga agcttatgag 12240 caggctgttg ctaatggtga ttctgaagtt gttcttaaaa agttgaagaa gtctttgaat 12300 gtggctaaat ctgaatttga ccgtgatgca gccatgcaac gtaagttgga aaagatggct 12360 gatcaagcta tgacccaaat gtataaacag gctagatctg aggacaagag ggcaaaagtt 12420 actagtgcta tgcagacaat gcttttcact atgcttagaa agttggataa tgatgcactc 12480 aacaacatta tcaacaatgc aagagatggt tgtgttccct tgaacataat acctcttaca 12540 acagcagcca aactaatggt tgtcatacca gactacaaca catataagaa tacgtgtgat 12600 ggtacaacat ttacttatgc atcagcattg tgggaaatcc aacaggttgt agatgcagat 12660 agtaaaattg ttcagcttag tgaaattagt atggacaatt cacctaattt agcatggcct 12720 cttattgtaa cagctttaag ggccaattct gctgtcaaat tacagaataa tgagcttagt 12780 cctgttgcac taagacaaat gtcttgtgct gccggtacta cacaaactgc ttgcactgat 12840 gacaatgcgt tagcttacta caacacaaca aagggaggta ggtttgtact tgcactgtta 12900 tccgatttac aggatttgaa atgggctaga ttccctaaga gtgatggaac tggtactatc 12960 tatacagaac tggaaccacc ttgtaggttt gttacagaca cacctaaagg tcctaaagtg 13020 aagtatcttt acttcatcaa aggattaaac aacctaaata gaggtatggt acttggtagt 13080 ttagctgcca cagtacgttt acaagctggt aatgcaacag aagttcctgc taattcaact 13140 gtactttctt tctgtgcttt tgctgtagat gctgctaaag cttacaaaga ttatctagct 13200 agtgggggac aaccaatcac taattgtgtt aagatgttgt gtacacacac tggtactggt 13260 caggcaataa cagttacacc ggaagccaat atggatcaag aatcctttgg tggtgcatcg 13320 tgttgtctgt actgccgttg tcatatagat catccaaatc ctaaaggatt ttgtgactta 13380 aaaggtaagt atgtacaaat acctacaact tgtgctaatg accctgtggg ttttacactt 13440 aaaaacacag tctgtaccgt ctgcggtatg tggaaaggtt atggttgtag ttgtgatcaa 13500 ctccgcgaac ccatgcttca gtcagctgat gcacaatcgt ttttaaacgg gtttgcggtg 13560 taagtgcagc ccgtcttaca ccgtgcggca caggcactag tactgatgtc gtatatagag 13620 cttttgacat ctacaatgat aaagtagctg gttttgctaa gttcctaaaa actaattgtt 13680 gtcgcttcca agaaaaggac gaagatgaca atctcattga ttcttacttt gtagttaaga 13740 gacacacttt ctctaactac caacatgaag aaacaattta caacctgctt aaggattgtc 13800 cagctgttgc taaacatgac ttctttaagt ttagaataga cggtgacatg gtaccacata 13860 tatcacgtca acgtcttact aaatacacaa tggcagacct cgtctatgct ttaaggcatt 13920 ttgatgaagg taattgtgac acattaaaag aaatacttgt cacatacaat tgttgtgatg 13980 atgactactt caataaaaag gactggtatg attttgtaga aaacccagat atattacgcg 14040 tatacgccaa cttaggtgaa cgtgtacgcc aagctttgtt aaaaacagta cagttctgtg 14100 atgccatgcg aaatgctggt attgttggtg tactgacatt agataatcaa gatctcaatg 14160 gtaactggta tgactttggt gatttcatac aaaccacgcc aggtagtgga gttcctgttg 14220 tagactctta ttattcattg ctcatgccta tattaacctt gaccagggct ttaactgcag 14280 agtcacatgt tgacactgac ttaacaaagc cttacattaa gtgggatttg ttaaaatacg 14340 acttcacgga agagaggtta aaactctttg accgttattt taaatactgg gatcagacat 14400 accacccaaa ttgtgttaac tgtttggatg acagatgcat tctgcattgt gcaaacttta 14460 atgttctgtt ctctacagtg ttcccaccta caagttttgg accactagtg agaaaaatat 14520 ttgttgatgg tgttccattt gtagtttcaa ctggatacca cttcagagag ctaggtgttg 14580 tacataatca ggatgtaaac ttacatagct ctagacttag ttttaaggaa ttacttgtgt 14640 atgctgctga tcctgctatg catgctgctt ctggtaatct attactagat aaacgcacta 14700 cgtgcttttc agtagctgca cttactaaca atgttgcttt tcaaactgtc aaacccggta 14760 attttaacaa ggacttctat gactttgctg tgtctaaggg tttctttaag gaaggaagtt 14820 ctgttgaatt aaaacacttc ttctttgctc aggatggtaa tgctgctatc agcgattatg 14880 actactatcg ttataatcta ccaacaatgt gtgatatcag acaactacta tttgtagttg 14940 aagttgttga taagtacttt gattgttacg atggtggctg tattaatgct aaccaagtca 15000 tcgtcaacaa cctagacaaa tcagctggtt ttccatttaa taaatggggt aaggctagac 15060 tttattatga ttccatgagt tatgaggatc aagatgcact tttcgcatat acaaaacgta 15120 atgtcatccc tactataact caaatgaacc ttaagtatgc cattagtgca aagaatagag 15180 ctcgcaccgt agctggtgtc tctatctgta gtactatgac caatagacag tttcatcaaa 15240 aattactcaa gtcaatagcc gccactagag gagctactgt agtaattgga acaagcaaat 15300 tctatggtgg ttggcacaac atgctcaaaa ctgtttatag tgatgtagaa aaccctcacc 15360 ttatgggttg ggattatcct aaatgtgata gagccatgcc taacatgctt agaattatgg 15420 cctcacttgt tcttgctcgc aaacatacaa cgtgttgtag cttgtcacac cgtttctata 15480 gattagctaa tgagtgtgct caagtattga gtgaaatggt catgtgtggc ggttcactat 15540 atgttaaacc aggtggaacc tcatcaggag atgccacaac tgcttatgct aatagtgtgt 15600 ttaacatttg tcaagctgtc acggccaatg ttaatgcact tttatctact gatggtaaca 15660 aaattgccga taagtatgtc cgcaatttac aacacagact ttatgagtgt ctctatagaa 15720 atagagatgt tgacacagac tttgtgaatg agttttacgc atatttgcgt aaacatttct 15780 caatgatgat actctctgac gatgctgttg tgtgtttcaa tagcacttat gcatctcaag 15840 gtctagtggc tagcataaag aactttaagt cagttcttta ctatcaaaac aacgttttta 15900 tgtctgaagc aaaatgttgg actgagactg accttactaa aggacctcat gaattttgct 15960 ctcaacatac aatgctagtt aaacagggtg atgattatgt gtaccttcct tacccagatc 16020 catcaagaat cctaggtgcc ggttgttttg tagatgatat cgtaaaaaca gatggtacac 16080 ttatgattga acggttcgtg tctttagcta tagatgctta cccacttact aaacatccta 16140 atcaggagta tgctgatgtc tttcatttgt acttacaata catacgtaag ctacatgatg 16200 agttaacagg acacatgtta gacatgtatt ctgttatgct tactaatgat aacacttcaa 16260 ggtattggga acctgagttt tatgaggcta tgtacacacc gcatacagtc ttacaagctg 16320 ttggtgcttg tgttctttgc aattcacaga cttcattaag atgtggtgct tgcatacgta 16380 gaccattctt atgttgtaaa tgctgttacg accatgtcat ctcaacatca cataaattag 16440 tcttgtctgt taatccgtat gtttgcaatg ctccaggttg tgatgtcaca gatgtgactc 16500 aactttactt aggaggtatg agctattact gtaagtcaca taaaccaccc attagttttc 16560 cattgtgtgc taatggacaa gtttttggtc tctacaagaa tacatgtgtt ggtagcgata 16620 atgttactga ctttaatgca attgcaacat gtgactggac aaatgctggt gattacattt 16680 tagctaacac ctgtactgaa agactcaagc tttttgcagc agaaacgctc aaagctactg 16740 aggagacatt taaactgtct tatggtattg ctactgtacg tgaagtgctg tctgacagag 16800 aattacatct ttcatgggaa gttggtaaac ctagaccacc acttaaccga aattatgtct 16860 ttactggtta tcgtgtaact aaaaacagta aagtgcaaat cggagagtac acctttgaaa 16920 aaggtgacta tggtgatgct gttgtttacc gaggtacaac aacttacaaa ctcaacgttg 16980 gtgattattt tgtgctgaca tcacatacag taatgccatt aagtgcacct acactagtgc 17040 cacaagagca ctatgttaga attactggct tatacccaac actcaatatc tcagatgagt 17100 tttctagcaa tgttgcaaat tatcaaaagg ttggtatgca aaagtattct acactccagg 17160 gaccacctgg tactggtaaa agtcattttg ctattggtct agctctctac tacccttctg 17220 ctcgcatagt atatacagct tgctctcatg cagctgttga tgcactatgt gagaaggcat 17280 taaaatattt gcccatagac aaatgtagta gaattatacc tgcacgtgct cgtgtagagt 17340 gttttgataa attcaaggtg aattcaacat tagaacagta tgtcttttgt actgtaaatg 17400 cattgcctga gacgacagca gatatagttg tctttgatga aatttcaatg gccacaaatt 17460 atgatttgag tgttgtcaat gccagattac gtgctaagca ctatgtgtac attggtgatc 17520 ctgctcaatt acctgcacca cgcacattac taactaaggg tacactagaa ccagaatatt 17580 tcaattcagt gtgtagactt atgaaaacta taggtccaga catgttcctc ggaacttgtc 17640 gtagatgtcc tgctgaaatt gttgacactg tgagtgcttt ggtttatgat aataagctta 17700 aggcacataa agacaaatca gctcaatgct ttaaaatgtt ctacaagggt gttatcacgc 17760 atgatgtttc atctgcaatt aacaggccac aaataggcgt ggtaagagaa ttccttacac 17820 gtaaccctgc ttggagaaaa gctgtcttta tttcacctta caattcccag aatgctgtag 17880 cctcaaagat tttgggacta ccaactcaaa ctgttgattc atcacagggc tcagaatatg 17940 actatgtcat attcactcaa accactgaaa cagctcactc ttgtaatgta aacagattca 18000 acgttgctat taccagagca aaagtaggca tactttgcat aatgtctgat agagaccttt 18060 atgacaagtt gcaatttaca agtcttgaaa ttccacgtag gaatgtggca actttacaag 18120 ctgaaaatgt aacaggactc tttaaagatt gtagtaaggt aatcactggg ttacatccta 18180 cacaggcacc tacacactta agtgttgata ctaaattcaa aactgaaggt ttatgtgttg 18240 acatacctgg catacctaag gacatgacct atagaagatt aatctctatg atgggtttca 18300 aaatgaatta ccaggttaat ggttacccta acatgtttat cacccgcgaa gaagctataa 18360 gacatgtacg tgcatggatt ggcttcgatg tcgaaggttg tcatgctact agagaagctg 18420 ttggtaccaa tttaccttta cagctaggtt tttctacagg tgttaaccta gttgctgtac 18480 ctacaggtta tgttgataca cctaataata cagatttttc cagagttagt gctaaaccac 18540 cgcctggaga tcaatttaaa cacctcatac cacttatgta caaaggactt ccttggaatg 18600 tagtgcgtat aaagattgtc caaatgttaa gtgacacact taaaaatctc tctgacagag 18660 tcgtatttgt cttatgggca catggctttg agttgacatc tatgaagtat tttgtgaaga 18720 tcggacctga gcgcacatgt tgtctatgtg atagacgtgc tacatgcttt tccactgctt 18780 cagacactta tgcctgttgg catcattcta ttggatttga ttacgtctat aatccgttta 18840 tgattgatgt tcaacaatgg ggttttacag gtaacctaca aagcaaccat gatctgtatt 18900 gtcaagtcca tggtaatgca catgtagcta gttgtgatgc aatcatgact aggtgtctag 18960 ctgtccacga gtgctttgtt aagcgtgttg actggactat tgaatatcct ataatcggtg 19020 atgaactgaa gattaatgcg gcttgtagaa aggttcaaca catggttgtt aaagctgcat 19080 tattagcaga caaattccca gttcttcacg acattggtaa ccctaaagct attaagtgtg 19140 tacctcaagc tgatgtagaa tggaagttct atgatgcaca gccttgtagt gacaaagctt 19200 acaaaataga agaactgttc tattcttatg ccacacattc tgacaaattc acagatggtg 19260 tatgcctatt ttggaattgc aatgtcgata gatatcctgc taattccatt gtttgtagat 19320 ttgacactag agtgctatct aaccttaact tgcctggttg tgatggtggc agtttgtatg 19380 taaataagca tgcattccac acaccagctt ttgataaaag tgcttttgtt aatctaaagc 19440 aacttccatt tttctattac tctgacagtc catgtgagtc tcatggaaaa caagtagtgt 19500 cagatataga ttatgtacca ctaaagtctg ctacgtgtat aacacgttgc aatttaggtg 19560 gtgctgtctg tagacatcat gctaatgagt acagattgta tctcgatgct tataacatga 19620 tgatctcagc tggctttagc ttgtgggttt acaaacaatt tgatacctat aacctctgga 19680 acacttttac aagacttcag agtttagaaa atgtggcttt taatgttgta aataagggac 19740 actttgatgg acaacagggt gaagtaccag tttctatcat taacaacact gtttacacaa 19800 aagttgatgg tgttgatgta gaattgtttg agaacaaaac cacattacct gttaatgtag 19860 catttgagct ttgggctaag cgcaacatta aaccagtacc agaggtgaaa atactcaata 19920 atttgggtgt ggacattgct gctaatactg tgatctggga ctacaaaaga gatgctccag 19980 cacatatatc tactattggt gtttgttcta tgactgacat agccaagaaa ccaactgaaa 20040 cgatttgtgc accactcact gtcttttttg atggtagagt tgatggtcaa gtagacttat 20100 ttagaaatgc ccgtaatggt gttcttatta cagaaggtag tgttaaaggt ttacaaccat 20160 ctgtaggtcc caaacaagct agtcttaatg gagtcacatt aattggagaa gccgtaaaaa 20220 cacagttcaa ttattacaag aaagtggatg gtgttgtcca acaattacct gaaacttact 20280 ttactcagag tagaaactta caggaattta agcccaggag tcaaatggaa attgatttct 20340 tagaacttgc tatggatgaa ttcattgaac ggtataaatt agaaggctat gccttcgaac 20400 atatcgttta tggagatttt agtcatagtc agttaggtgg tttacatcta ctgattggac 20460 tagctaaacg ttttaaggaa tcaccttttg aacttgaaga ttttattcct atggacagta 20520 cagttaaaaa ctacttcata acagatgcgc aaacaggttc atctaagtgt gtgtgttctg 20580 ttattgatct tttacttgat gacttcgttg aaataataaa gtcccaagat ttatctgtag 20640 tttctaaggt tgtcaaagtg actattgact atacagaaat ctcatttatg ctttggtgta 20700 aagatggcca tgtagaaaca ttttacccaa aattacaatc tagtcaagcg tggcaaccgg 20760 gtgttgctat gcctaatctt tacaaaatgc aaagaatgct attagaaaag tgtgaccttc 20820 aaaattatgg tgatagtgca acattaccta aaggcataat gatgaatgtc gcaaaatata 20880 ctcaactgtg tcaatattta aacacactga cattagctgt accctataat atgagagtta 20940 tccattttgg tgctggttct gataaaggag ttgcaccagg tacagctgtt ttaagacaat 21000 ggttgcctac aggtacgctg cttgtcgatt cagatcttaa tgactttgtc tctgatgcag 21060 attcaacttt gattggtgat tgtgcaactg tacatacagc taataaatgg gatctcatta 21120 ttagtgatat gtacgaccct aagactaaga atgtcacaaa agaaaacgac tctaaagagg 21180 gttttttcac ttacatttgt gggtttatac aacaaaagct agctcttgga ggttccgtgg 21240 ctataaagat aacagaacat tcttggaatg ctgatcttta taagctcatg ggacacttcg 21300 catggtggac agcctttgtt actaatgtga atgcgtcatc atctgaagca tttttaatcg 21360 gatgtaacta ccttggcaaa ccacgcgaac aaatagatgg ttatgtcatg catgcaaatt 21420 acatattttg gaggaataca aatccaattc agctttcttc ttattcttta ttcgacatga 21480 gtaaattccc ccttaaatta aggggtactg ctgttatgtc tttaaaagaa ggtcaaatca 21540 atgatatgat tctctctctt cttagtaaag gtagacttat aattagagaa aacaacagag 21600 ttgttatttc tagtgatgtt cttgttaaca actaaacgaa caatgtttgt ttttcttgtt 21660 ttattgccac tagtctctag tcagtgtgtt aatcttacaa ccagaactca attaccccct 21720 gcatacacta attctttcac acgtggtgtt tattaccctg acaaagtttt cagatcctca 21780 gttttacatt caactcagga cttgttctta cctttctttt ccaatgttac ttggttccat 21840 gctatacatg tctctgggac caatggtact aagaggtttg ataaccctgt cctaccattt 21900 aatgatggtg tttactttgc ttccactgag aagtctaaca taataagagg ctggattttt 21960 ggtactactt tagattcgaa aacccagtcc ctacttattg ttaataacgc tactaatgtt 22020 gttatcaaag tctgtgaatt tcaattttgt aacgatccat ttttgggtgt ttattaccac 22080 aaaaacaaca aaagttggat ggaaagtgag ttcagagttt attctagtgc gaataattgc 22140 acttttgaat acgtctctca gccttttctt atggaccttg aaggaaaaca gggtaatttc 22200 aaaaatctta gggaatttgt gttcaagaat attgatggtt acttcaagat atactctaag 22260 cacacgccta ttaatttagt gcgtgatctc cctcagggtt tttcggcttt agaaccattg 22320 gtagatttgc caataggtat taacatcact aggtttcaaa ctttacttgc tttacataga 22380 agttatttaa ctcctggtga ttcttcttca ggttggacag ctggtgctgc agcttattat 22440 gtgggttatc ttcaacctag gacttttcta ctgaagtaca atgaaaatgg aaccattaca 22500 gatgctgtag actgtgcact tgaccctctc tcagaaacaa agtgtacgtt gaaatccttc 22560 actgtagaaa aaggaatcta tcaaacttct aactttagag tccaaccaac agaatctatt 22620 gttagatttc ctaacatcac aaacttgtgc ccttttggtg aagtttttaa cgccaccaga 22680 tttgcatctg tttatgcttg gaacaggaag agaatcagca actgtgttgc tgattattct 22740 gtcctgtata attccgcatc attttccact tttaagtgtt atggagtgtc tcctactaaa 22800 ttaaatgatc tctgctttac taatgtctat gcagattcat ttgtaattag aggtgatgaa 22860 gtcagacaaa tcgctccagg gcaaactgga aagattgctg attataacta caaattacca 22920 gatgatttta caggctgcgt tatagcttgg aattctaaca atcttgattc taaggttggt 22980 ggtaattata attacctgta cagattgttt aggaagtcta atctcaaacc ttttgagaga 23040 gatatttcaa ctgaaatcta tcaggccggt agcacacctt gtaatggtgt tgaaggtttt 23100 aattgttact ttcctctgca atcatatggt ttccaaccca ctaatggtgt tggttaccaa 23160 ccatacagag tagtagtact ttcttttgaa cttctacatg caccagcaac tgtttgtgga 23220 cctaaaaagt ctactaattt ggttaagaac aagtgtgtca atttcaactt caatggttta 23280 acaggcacag gtgttcttac tgagtctaac aaaaagtttc tgcctttcca acaatttggc 23340 agagacattg ctgacactac tgatgctgtt cgtgatccac aaacacttga gattcttgac 23400 attacaccat gttcttttgg tggtgtcagt gttataacac caggaacaaa tacttctaac 23460 caggttgctg ttctttatca ggatgttaac tgcacagaag tccctgttgc tattcatgca 23520 gatcaactta ctcctacttg gcgtgtttat tctacaggtt ctaatgtttt tcaaacacgt 23580 gcaggctgtt taataggggc tgaacatgtc aacaactcat atgagtgtga catacccatt 23640 ggtgcaggta tatgcgctag ttatcagact cagactaatt ctcctcggag agcaagaagt 23700 gtagctagtc aatccatcat tgcctacact atgtcacttg gtgcagaaaa ttcagttgct 23760 tactctaata actctattgc catacccaca aattttacta ttagcgttac cacagaaatt 23820 ctaccagtgt ctatgaccaa gacatcagta gattgtacaa tgtacatttg tggtgattca 23880 actgaatgca gcaatctttt gttgcaatat ggcagttttt gtacacaatt aaaccgtgct 23940 ttaactggaa tagctgttga acaagacaaa aacacccaag aagtttttgc acaagtcaaa 24000 caaatttaca agacaccacc aattaaagat tttggcggtt ttaattttag ccagatactg 24060 ccagatccat caaaaccaag caagaggtca tttattgaag atctactgtt caacaaagtg 24120 acacttgcag atgctggctt catcaaacaa tatggtgatt gccttggtga tattgctgct 24180 agagacctca tttgtgcaca aaagtttaac ggccttactg ttttgccacc tttgctcaca 24240 gatgaaatga ttgctcaata cacttctgca ctgttagcag gtacaatcac ttctggttgg 24300 acttttggtg caggtgctgc attacaaata ccatttgcta tgcaaatggc ttataggttt 24360 aatggtattg gagttacaca gaatgttctc tatgagaacc aaaaattgat tgccaaccaa 24420 tttaatagtg ctattggcaa aattcaagac tcactttctt ccacagcaag tgcacttgga 24480 aaacttcaag atgtggtcaa ccaaaatgca caagctttaa acacgcttgt taaacaactt 24540 agctccaatt ttggtgcaat ttcaagtgtt ttaaacgaca tcctttcacg tcttgacaaa 24600 gttgaggctg aagtgcaaat tgataggttg atcacaggca gacttcaaag tttgcagaca 24660 tatgtgactc aacaattaat tagagctgca gaaatcagag cttctgctaa tcttgctgct 24720 actaaaatgt cagagtgtgt acttggacaa tcaaaaagag ttgacttttg cggaaagggc 24780 tatcatctta tgtcatttcc tcagtcagca cctcatggtg tcgtcttttt gcatgtgact 24840 tatgtccctg cacaagaaaa gaacttcaca actgctcctg ccatttgtca tgatggaaaa 24900 gcacactttc ctcgtgaagg tgtctttgtt tcaaatggca cacactggtt tgtaacacaa 24960 aggaattttt atgaaccaca aatcattact acagacaaca catttgtgtc tggtaactgt 25020 gatgttgtaa taggaattgt caacaacaca gtttatgatc ctttgcaacc tgaattagac 25080 tcattcaagg aggagcttga taaatacttc aagaaccata cctcaccaga tgttgattta 25140 ggtgacatct ctggcattaa tgcttcagtt gtaaacattc agaaagaaat cgaccgcctc 25200 aatgaggttg ccaagaattt aaatgaatct ctcatcgatc tccaagaact tggaaagtat 25260 gagcagtata taaaatggcc atggtacatt tggctaggtt ttatagctgg cttgattgcc 25320 atagtaatgg tgacaattat gctttgctgt atgaccagtt gctgtagttg tctcaagggc 25380 tgttgttctt gtggatcctg ctgcaaattt gacgaggacg actctgagcc agtgctcaaa 25440 ggagtcaaat tacattacac ataaacgaac ttatggattt gtttatgaga atcttcacaa 25500 ttggaactgt aactttgaag caaggtgaaa tcaaggatgc tactccttca gattttgtta 25560 gagctactgc aacgataccg atacaagcat cacttccttt cggatggctt attgttggcg 25620 ttgcacttct tgctgttttt cagagcgctt ccaaaatcat aaccctcaaa aagagatggc 25680 aactagcact ctccaagggt gttcactttg tttgcaactt gctgttgttg tttgtaacag 25740 tttactcaca tcttttgctt gttgctgctg gccttgaagc cccttttctc tatctttatg 25800 ctttagtcta cttcttgcag agtataaact ttgtacgcat aataatgagg ctttggcttt 25860 gctggaaatg ccgttccaaa aacccattac tttatgatgc caactatttt ctttgctggc 25920 atactaattg ttacgactat tgtatacctt acaatagtgt aacttcttca attgtcatta 25980 cttcaggtga tggcacaaca agtcctattt ctgaacatga ctaccagatt ggtggttata 26040 ctgaaaaatg ggaatctgga gtaaaagact gtgttgtatt acacagttac ttcacttcag 26100 actattacca gctgtactca actcaattga gtacagacac tggtgttgaa catgttacct 26160 tcttcatcta caataaaatc gttgatgagc ctgaagaaca tgtccaaatt cacacaatcg 26220 acgtttcatc cggagttgtt aatccagtaa tggaaccaat ttatgatgaa ccgacgacga 26280 ctactagcgt gcctttgtaa gcacaagctg atgagtacga acttatggca gattccaacg 26340 gtactattac cgttgaggag ctgaaaaagc tccttgaaca atggaaccta gtaataggtt 26400 tcctattcct tacatggatt tgcctgctgc aatttgccta tgccaacagg aataggtttt 26460 tgtacatcat taagttgatt ttcctctggc tgttatggcc agtaacttta gcttgttttg 26520 tgcttgctgc tgtttacaga ataaattgga tcaccggtgg aattgctatt gcaatggctt 26580 gtcttgtagg attgatgtgg ctaagctact tcattgcttc tttcagactg tttgcgcgta 26640 cgcgttccat gtggtcattc aatccagaaa ctaacattct tctcaacgtg ccactccatg 26700 gaactattct gactagaccg cttctagaaa gtgaactcgt aatcggagct gttatccttc 26760 gtggacatct tcgtattgct ggacatcatc taggacgctg tgacatcaag gatctaccta 26820 aagaaatcac tgttgctaca tcacgaacgc tttcttatta caaattggga gcttcacagc 26880 gtgtagcagg tgattcaggt tttgctgcat atagtcgcta caggattggc aactataaat 26940 taaacacaga ccattccagt agcagtgaca atattgcttt gcttgtacag taaacgaaca 27000 tgaaaattat tcttttcttg gcactgataa cactcgctac ttgtgagctt tatcactacc 27060 aagagtgtgt tagaggtaca acagtacttt taaaagaacc ttgctcgtcg ggaacatacg 27120 agggcaattc accatttcat cctctagctg ataacaaatt tgcactgact tgctttagca 27180 ctcaatttgc ttttgcttgt cctgacggcg taaaacacgt ctatcagtta cgtgccagat 27240 cagtttcacc taaactgttc atcagacaag aggaagttca agaactttac tctccaattt 27300 ttcttattgt tgcggcaata gtgtttataa cactttgctt cacactcaaa agaaagacag 27360 aatgattgaa ctttcattaa ttgacttcta tttgtgcttt ttagcctttc tgctattcct 27420 tgttttaatt atgcttatta tcttttggtt ctcacttgaa ctgcaagatc ataatgaaac 27480 ttgtcacgcc taagacgttc gtgttgtttt agatttcatc taaacgaaca aactaaaatg 27540 tctgataatg gacctcaaaa tcagcgaaat gcacctcgca ttacgtttgg tggaccatca 27600 gattcaactg gcagtaacca gaatggagaa cgaagtggtg cgcgatcaaa acaacgccgc 27660 ccgcaaggtt tacccaataa tactgcgtct tggttcaccg ctctcactca acatggcaag 27720 gaagatttaa aattccctcg aggacaaggc gttccaatta acaccaatag cagtccagat 27780 gaccaaattg gctactaccg ccgcgccaca agacgaattc gtggtggtga tggtaaaatg 27840 aaagatctca gtccaagatg gtatttctac tatctaggaa ctgggccaga agctggactt 27900 ccttatggtg ctaacaaaga tggcatcata tgggttgcaa ctgagggagc cttgaataca 27960 ccaaaagatc acattggcac cagaaatcct gctaacaatg ctgcaatcgt gctacaactt 28020 cctcaaggaa caacattacc aaaaggtttt tacgcagaag ggtctagagg tggaagtcaa 28080 gcctcttcta gatcatcatc acgtagtcgc aacagttcaa gaaattcaac tccaggttca 28140 agtagaggaa cttctcctgc tagaatggct ggaaatggag gtgatgctgc tcttgctttg 28200 ttactacttg acagattgaa ccagcttgag agcaaaatgt ctggtaaagg ccaacaacaa 28260 caaggccaaa ctgtcactaa gaaatctgct gctgaggctt ctaagaagcc tagacaaaaa 28320 cgtactgcca ctaaagcata caatgtaaca caagctttcg gcagacgtgg tccagaacaa 28380 actcaaggaa attttgggga tcaggaacta atcagacaag gaactgatta caaacattgg 28440 ccgcaaattg cacaatttgc tccttctgct tcagcgttct ttggaatgtc gagaattgga 28500 atggaagtca caccttcggg aacatggttg acctatacag gtgccatcaa attggatgac 28560 aaagatccaa atttcaaaga tcaagtcatt ttgctgaata agcatattga cgcatacaaa 28620 acattcccac caacagagcc taaaaaggac aaaaagaaga aggctgatga aactcaagcc 28680 ttaccgcaga gacagaagaa acagcaaact gtgactcttc ttcctgctgc agatttggat 28740 gatttctcca aacaattgca acaatccatg agcagtgctg actcaactca ggcctaaact 28800 catgcagacc acacaaggca gatgggctat ataaacgttt tcgcttttcc gtttacgata 28860 tatagtctac tcttgtgcag aatgaattct cgtaactaca tagcacaagt agatgtagtt 28920 aactttaatc tcacatagca atctttaatc agtgtgtaac attagggagg acttgaaaga 28980 gccaccacat tttcaccgag gccacgcgga gtacgatcga gtgtacagtg aacaatgcta 29040 gggagagctg cctatatgga agagccctaa tgtgtaaaat taattttagt agtgctatcc 29100 ccatgtgatt ttaatagctt cttaggagaa tgacaaaaaa aaacaaaaaa aa 29152 <210> 44 <211> 29968 <212> DNA <213> Artificial Sequence <220> <223> Synthesis optimized <400> 44 caaatataac gaaaggctca gtcgaaagac tgggcctttc gttttatctg ttgtttgtcg 60 taatacgact cactataggg attaaaggtt tataccttcc caggtaacaa accaaccaac 120 tttcgatctc ttgtagatct gttctctaaa cgaactttaa aatctgtgtg gctgtcactc 180 ggctgcatgc ttagtgcact cacgcagtat aattaataac taattactgt cgttgacagg 240 acacgagtaa ctcgtctatc ttctgcaggc tgcttacggt ttcgtccgtg ttgcagccga 300 tcatcagcac atctaggttt cgtccgggtg tgaccgaaag gtaagatgga gagccttgtc 360 cctggtttca acgagaaaac acacgtccaa ctcagtttgc ctgttttaca ggttcgcgac 420 gtgttagtac gtggttttgg agattcagtg gaagaagtct tatcagaggc acgtcaacat 480 cttaaagatg gcacttgtgg cttagtagaa gttgaaaaag gcgttttgcc tcaacttgaa 540 cagccctatg tgttcatcaa acgttctgat gctagaactg cacctcatgg tcatgttatg 600 gttgagctgg tagcagaatt agaaggtatt cagtacggtc gtagtggtga gacattaggt 660 gttttagttc ctcatgtggg cgaaatacca gtggcttacc gcaaagttct tcttagaaag 720 aacggtaata aaggagctgg tggccatagt tacggcgctg atttaaagtc atttgactta 780 ggcgacgagc ttggcactga tccttatgaa gatttccaag aaaactggaa cactaaacat 840 agcagtggtg ttacccgtga actcatgcgt gagttaaatg gaggtgcata cactcgctat 900 gtcgataaca acttctgtgg acctgatggt taccctcttg agtgcattaa agaccttcta 960 gcacgtgctg gtaaagcttc atgcactttg tccgaacaac tggactttat tgacactaag 1020 aggggtgtat actgctgccg tgaacatgag catgaaattg cttggtacac ggaacgttct 1080 gaaaagagct atgaattgca gacacctttt gaaattaaac tggcaaagaa atttgacacc 1140 ttcaatgggg aatgtccaaa ttttgtattt cccctcaatt ccataatcaa gactattcaa 1200 ccaagggttg aaaagaaaaa gcttgatggc tttatgggta gaattcgatc tgtctatcca 1260 gttgcgtcac caaatgaatg caaccaaatg tgcctttcaa ctctcatgaa gtgtgatcat 1320 tgtggtgaaa cttcatggca gacgggcgat tttgttaaag ccacttgcga attttgtggc 1380 actgagaatt tgactaaaga aggtgccact acttgtggtt acttacccca aaatgctgtt 1440 gttaaaattt actgtccagc atgtcacaat tcagaagtag gacctgagca tagtcttgcc 1500 gaataccata atgaatctgg cttgaaaacc attcttcgta agggtggtcg cactattgct 1560 tttggaggat gtgtgttctc ttatgttggt tgccataaca agtgtgctta ttgggttcca 1620 cgtgcttcag ctaacatagg ttgtaaccat acaggtgttg ttggagaagg ttccgaaggt 1680 cttaatgaca accttcttga aatactccaa aaagagaaag tcaacatcaa tattgttggt 1740 gactttaaac ttaatgaaga gatcgccatt attttggcat ctttttctgc ttccacaagt 1800 gcttttgtgg aaactgtgaa aggtttggat tataaagcat tcaaacagat tgttgaatcc 1860 tgtggtaatt ttaaggttac aaagggaaaa gctaaaaaag gtgcctggaa tattggtgaa 1920 cagaaatcaa tactgagtcc tctttatgca tttgcatcag aggctgctcg tgttgtacga 1980 tcaattttct cccgcactct tgaaactgct caaaattctg tgcgtgtttt acagaaggcc 2040 gctataacaa tactagatgg aatttcacag tattcactga gactcattga tgctatgatg 2100 ttcacatctg atttggctac taacaatcta gttgtaatgg cctacattac aggtggtgtt 2160 gttcagttga cttcgcagtg gctaactaac atctttggca ctgtttatga aaaactcaaa 2220 cccgtccttg attggcttga agagaagttt aaggaaggtg tagagtttct tagagacggt 2280 tgggagattg ttaaattcat ctcaacctgt gcttgtgaaa ttgtcggtgg acaaattgtc 2340 acctgtgcta aggaaattaa ggagagtgtt cagacattct ttaagcttgt aaacaagttt 2400 ttggctttgt gtgctgactc tatcattatt ggtggagcta aacttaaagc cttgaattta 2460 ggtgaaacat ttgtcacgca ctcaaaggga ttgtacagaa agtgtgttaa atccagagaa 2520 gaaactggcc tactcatgcc tctaaaagcc ccaaaagaaa ttatcttctt agagggagaa 2580 acacttccca cagaagtgtt aacagaggaa gttgtcttga aaactggtga tttacaacca 2640 ttagaacaac ctactagtga agctgttgaa gctccattgg ttggtacacc agtttgtatt 2700 aacgggctta tgttgctcga aatcaaagac acagaaaagt actgtgccct tgcacctaat 2760 atgatggtaa caaacaatac cttcacactc aaaggcggtg caccaacaaa ggttactttt 2820 ggtgatgaca ctgtgataga agtgcaaggt tacaagagtg tgaatatcac ttttgaactt 2880 gatgaaagga ttgataaagt acttaatgag aagtgctctg cctatacagt tgaactcggt 2940 acagaagtaa atgagttcgc ctgtgttgtg gcagatgctg tcataaaaac tttgcaacca 3000 gtatctgaat tacttacacc actgggcatt gatttagatg agtggagtat ggctacatac 3060 tacttatttg atgagtctgg tgagtttaaa ttggcttcac atatgtattg ttctttctac 3120 cctccagatg aggatgaaga agaaggtgat tgtgaagaag aagagtttga gccatcaact 3180 caatatgagt atggtactga agatgattac caaggtaaac ctttggaatt tggtgccact 3240 tctgctgctt tacaacctga agaagaacaa gaagaagatt ggttagatga tgatagtcaa 3300 caaactgttg gtcaacaaga cggcagtgag gacaatcaga caactactat tcaaacaatt 3360 gttgaggttc aacctcaatt agagatggaa cttacaccag ttgttcagac tattgaagtg 3420 aatagtttta gtggttatct taaacttact gacaatgtat acatcaagaa tgcagacatt 3480 gtggaagaag ctaaaaaggt aaaaccaaca gtggttgtta atgcagccaa tgtttacctt 3540 aaacatggag gaggtgttgc aggagcctta aataaggcta ctaacaatgc catgcaagtt 3600 gaatctgatg attacatagc tactaatgga ccacttaaag tgggtggtag ttgtgtttta 3660 agcggacaca atcttgctaa acactgttta catgttgtcg gcccaaatgt taacaaaggt 3720 gaagatattc aacttcttaa gagtgcttat gaaaatttta accagcacga agttctactt 3780 gcaccattat tatcagctgg tatttttggt gctgacccta tacattcttt aagagtttgt 3840 gtagatactg ttcgcacaaa tgtctactta gctgtctttg ataaaaatct ctatgacaaa 3900 cttgtttcaa gctttttgga aatgaagagt gaaaagcaag ttgaacaaaa gatcgctgag 3960 attcctaaag aggaagttaa gccatttata actgaaagta aaccttcagt tgaacagaga 4020 aaacaagatg ataagaagat caaagcttgt gttgaagaag ttacaacaac tctggaagaa 4080 actaagttcc tcacagaaaa cttgctcctt tatatcgaca ttaatggcaa tcttcatcca 4140 gattctgcca ctcttgttag tgacattgac atcactttct taaagaaaga tgctccatat 4200 atagtgggtg atgttgttca agagggtgtt ttaactgctg tggttatacc tactaaaaag 4260 gctggtggca ctactgaaat gctagcgaaa gctttgagaa aagtgccaac agacaattat 4320 ataaccactt acccgggtca gggtttaaat ggttacactg tagaggaggc aaagacagtg 4380 cttaaaaagt gtaaaagtgc cttttacatt ctaccatcta ttatctctaa tgagaagcaa 4440 gaaattcttg gaactgtttc ttggaatttg cgagaaatgc ttgcacatgc agaagaaaca 4500 cgcaaattaa tgcctgtctg tgtggaaact aaagccatag tttcaactat acagcgtaaa 4560 tataagggta tcaagataca agagggtgtg gttgattatg gtgctagatt ttacttttac 4620 accagtaaaa caactgtagc gtcacttatc aacacactta acgatctaaa tgaaactctt 4680 gttacaatgc cacttggcta tgtaacacat ggcttaaatt tggaagaagc tgctcggtat 4740 atgagatctc tcaaagtgcc agctacagtt tctgtttctt cacctgatgc tgttacagcg 4800 tataatggtt atcttacttc ttcttctaaa acacctgaag aacattttat tgaaaccatc 4860 tcacttgctg gttcctataa agattggtcc tattctggac aatctacaca actaggtata 4920 gaatttctta agagaggtga taaaagtgta tattacacgt ccaatcctac cacattccac 4980 ctagatggtg aagttatcac ctttgacaat cttaagacac ttctttcttt gagagaagtg 5040 aggactatta aggtgtttac aacagtagac aacattaacc tccacacgca agttgtggac 5100 atgtcaatga catatggaca acagtttggt ccaacttatt tggatggagc tgatgttact 5160 aagataaaac ctcataactc acatgaaggt aaaacatttt acgttttgcc taatgatgac 5220 actctacgtg ttgaggcttt tgagtactac cacacaactg atcctagttt tctgggtagg 5280 tacatgtcag cattaaatca cactaaaaag tggaaatacc cacaagttaa tggtttaact 5340 tcgattaaat gggcagataa caactgttat cttgccactg cattgttaac actccaacaa 5400 atagagttga agtttaatcc acctgctcta caagatgctt attacagagc aagggctggt 5460 gaagctgcta acttttgtgc acttatctta gcctactgta ataagacagt aggtgagtta 5520 ggtgatgtta gagaaacaat gagttacttg tttcaacatg ccaatttaga ttcttgcaaa 5580 agagtcttga acgtggtgtg taaaacttgt ggacaacagc agacaaccct taagggtgta 5640 gaagctgtta tgtacatggg cacactttct tatgaacaat tcaagaaagg tgttcagata 5700 ccttgtacgt gtggtaaaca agctacaaaa tatctagtac aacaggagtc accttttgtt 5760 atgatgtcag caccacctgc tcagtatgaa cttaagcatg gtacatttac ttgtgctagt 5820 gagtacactg gtaattacca gtgtggtcac tataagcata taacttctaa ggaaactttg 5880 tattgcatag acggtgcttt acttacaaag tcctcagaat acaaaggtcc tattacggat 5940 gttttctaca aagaaaacag ttacacaaca accataaaac cagttactta taagttggat 6000 ggtgttgttt gtacagaaat tgaccctaag ttggacaatt attataagaa ggacaactct 6060 tatttcacag agcaaccaat tgatcttgta ccaaaccaac catatccaaa cgcaagcttc 6120 gataatttta agttcgtatg cgataatatc aaatttgctg atgatctcaa ccagttaact 6180 ggttataaga aacctgcttc aagagagctt aaagttacat ttttccctga cttaaatggt 6240 gatgtggtgg ctattgatta taaacactac acaccctctt ttaagaaagg agctaaattg 6300 ttacataagc ctattgtttg gcatgttaac aatgcaacta ataaagccac gtataaacca 6360 aatacctggt gtatacgttg tctttggagc acaaaaccag ttgaaacatc aaattcgttt 6420 gatgtactga agtcagagga cgcgcaggga atggataatc ttgcatgtga agatctaaaa 6480 ccagtctctg aagaagtagt ggaaaatcct accatacaga aagacgttct tgagtgtaat 6540 gtgaaaacta ccgaagttgt aggagacatt atacttaaac cagcaaataa tagtttgaag 6600 atcacagaag aggttggcca cacagatcta atggctgctt atgtagacaa ttctagtctt 6660 actattaaga aacctaatga actctctaga gtattaggtt tgaaaaccct tgctactcat 6720 ggtttagctg ctgttaatag tgtcccttgg gatactatag ctaattatgc taagcctttt 6780 cttaacaaag ttgttagtac aactactaac atagttacac ggtgtcttaa tcgtgtttgt 6840 actaattata tgccttactt ctttacttta ttgctacaat tgtgtacttt tactagaagt 6900 acaaattcta gaatcaaggc atctatgccg actactatag caaagaatac tgttaagagt 6960 gtcggtaaat tttgtctaga ggcttcattt aattatctca agtcacctaa cttttctaag 7020 ctgataaaca ttatcatctg gtttttgcta ttaagtgttt gcctaggttc tttaatctac 7080 tcaaccgctg ctttaggtgt tttaatgtct aatttaggca tgccttctta ctgtactggt 7140 tacagagaag gctatttgaa ctctactaat gtcactattg caacctactg tactggatct 7200 ataccttgta gtgtttgtct tagtggttta gattctttag acacctatcc ttctcttgaa 7260 actatacaga ttaccatttc atctttcaaa tgggatttaa ctgcttttgg cttagttgca 7320 gagtggtttt tggcatatat tcttttcact aggtttttct atgtacttgg attggctgca 7380 atcatgcaat tgtttttcag ctattttgca gtccatttta ttagtaactc ttggcttatg 7440 tggcttataa ttaatcttgt gcagatggcc ccgatttcag ctatggttag aatgtacatc 7500 ttctttgcct cattttatta tgtgtggaaa agttatgtgc atgttgtaga cggttgtaat 7560 tcatcaactt gtatgatgtg ttacaaacgt aatagagcaa caagagtcga atgtacaact 7620 attgttaatg gtgttagaag gtccttttat gtctatgcta atggaggtaa aggcttttgc 7680 aaactacaca attggaattg tgttaattgt gatacattct gtgctggtag tacatttatt 7740 agtgatgaag ttgcgagaga cttgtcacta cagtttaaaa gaccaataaa tcctactgac 7800 caatcttctt acatcgttga tagtgttaca gtgaagaatg gttccatcca tctttacttt 7860 gataaagctg gtcaaaagac ttatgaaaga cattctctct ctcattttgt taacttagac 7920 aacctgagag ctaataacac taaaggttca ttgcctatta atgttatcgt tttcgacggt 7980 aaatcaaaat gtgaagaatc atctgcaaaa tcagcgtctg tttactacag tcagcttatg 8040 tgtcaaccta tactgttact agatcaggca ttagtgtctg atgttggtga tagtgcggaa 8100 gttgcagtta aaatgtttga tgcttacgtt aatacgtttt catcaacttt taacgtacca 8160 atggaaaaac tcaaaacact agttgcaact gcagaagctg aacttgcaaa gaatgtgtcc 8220 ttagacaatg tcttatctac gtttatttca gcagctcggc aagggtttgt tgattcagat 8280 gtagaaacta aagatgttgt tgaatgtctt aaattgtcac atcaatctga catagaagtt 8340 actggcgata gttgtaataa ctatatgctc acctataaca aagttgaaaa catgacaccc 8400 cgtgaccttg gtgcttgtat tgactgtagt gctagacata ttaatgcgca ggtagcaaaa 8460 agtcacaaca ttgctttgat atggaacgtt aaagatttca tgtcattgtc tgaacaacta 8520 cgaaaacaaa tacgtagtgc tgctaaaaag aataacttac ccttcaagtt gacatgtgca 8580 actactagac aagttgttaa tgttgtaaca acaaagatag cacttaaggg tggtaaaatt 8640 gtgaataact ggttgaagca gcttattaaa gttacacttg tgttcctttt tgttgctgct 8700 attttctatc tgataacacc tgttcatgtc atgtctaaac atactgactt ttcaagtgaa 8760 atcataggat acaaggctat tgatggtggt gtcactcgtg acatagcatc tacagatact 8820 tgttttgcta acaaacatgc tgattttgac acatggttta gccagcgtgg tggtagttat 8880 actaatgaca aagcttgccc attgattgct gcagtcataa caagagaagt gggttttgtc 8940 gttcctggtt tgcctggaac gatattacgc acaactaatg gtgacttttt gcatttctta 9000 cctagagttt ttagtgcagt tggtaacatc tgttacacac catcaaaact tatagagtac 9060 actgactttg caacatcagc ttgtgttttg gctgctgaat gtacaatttt taaagacgct 9120 tctggtaagc cagtaccata ttgttatgat accaatgtac tagaaggttc tgttgcttat 9180 gaaagtttac gccctgacac acgttatgtg ctcatggatg gctctattat tcaatttcct 9240 aacacctacc ttgaaggttc tgtaagagtg gtaacaactt ttgattctga gtactgtagg 9300 cacggcactt gtgaaagatc agaagctggt gtttgtgtat ctactagtgg tagatgggta 9360 cttaacaacg attattacag atctttacca ggagttttct gtggtgtaga tgctgtaaat 9420 ttgcttacta acatgtttac accactaatt caacctattg gtgctttgga catatcagca 9480 tctatagtag ctggtggtat tgtagctatc gtagtaacat gccttgccta ctattttatg 9540 aggtttagac gtgcttttgg tgaatacagt catgtagttg cctttaatac tctcctattc 9600 cttatgtcat tcactgtact ctgtttaaca ccagtttact cattcttacc tggtgtttat 9660 tctgttattt acctgtactt gacattttat ctgactaatg atgtttcttt tctcgcacat 9720 attcagtgga tggttatgtt cacaccttta gtacctttct ggataacaat tgcttacatc 9780 atttgtattt ccacaaagca tttctattgg ttctttagta attacctaaa gagacgtgta 9840 gtctttaatg gtgtttcctt tagtactttt gaagaagctg cgctgtgcac ctttttgtta 9900 aataaggaga tgtatctaaa gttgcgtagt gatgtgctat tacctcttac gcaatataat 9960 agatacttag ctctttataa caagtacaag tatttcagtg gagcaatgga tacaactagc 10020 tacagagaag ctgcttgttg tcatctcgca aaggctctca atgacttcag taactcaggt 10080 tctgatgttc tttaccaacc accacaaacc tctatcacct cagctgtttt gcagagtggt 10140 tttagaaaaa tggcattccc atctggtaaa gttgagggtt gtatggtaca agtaacttgt 10200 ggtacaacta cacttaacgg tctttggctt gatgacgtag tttactgtcc aagacatgtg 10260 atctgcacct ctgaagatat gcttaaccct aattatgaag atctactcat ccgtaagtct 10320 aatcataact tcttggtaca ggctggtaat gttcaactca gggttattgg acattctatg 10380 caaaattgtg tacttaagct taaggttgat acagccaatc ctaagacacc taagtataag 10440 tttgttcgca ttcaaccagg acagactttt tcagtgttag cttgttacaa tggttcacca 10500 tctggtgttt accaatgtgc tatgaggccc aatttcacta ttaagggttc attccttaat 10560 ggttcatgtg gtagtgttgg ttttaacata gattatgact gtgtctcttt ttgttacatg 10620 caccatatgg aattaccaac tggagttcat gctggcacag acttagaagg taacttttat 10680 ggaccttttg ttgacaggca aacagcacaa gcagctggta cagatacaac tattacagtt 10740 aatgttcttg cttggttgta cgctgctgtt ataaatggag acaggtggtt tctcaatcga 10800 tttaccacaa ctcttaatga ctttaacctt gtggctatga agtacaatta tgaacctcta 10860 acacaagacc atgttgacat actaggacct ctttctgctc aaactggaat tgccgtttta 10920 gatatgtgtg cttcattaaa agaacttctg caaaatggta tgaatggacg taccatattg 10980 ggtagtgctt tattagaaga tgagtttaca ccttttgatg ttgttagaca atgctcaggt 11040 gttactttcc aaagtgcagt gaaaagaaca atcaagggta cacaccactg gttgttactc 11100 acaattttga cttcactttt agttttagtc cagagtactc aatggtcttt gttctttttc 11160 ttctacgaaa atgccttttt accttttgct atgggtatta ttgctatgtc tgcttttgca 11220 atgatgtttg tcaaacataa gcatgcattt ctctgtttgt ttttgttacc ttctcttgcc 11280 actgtagctt actttaatat ggtctacatg cctgctagtt gggtgatgcg tattatgaca 11340 tggttggata tggttgatac tagtttgtct ggttttaagc taaaagactg tgttatgtat 11400 gcatcagctg tagtgttact aatccttatg acagcaagaa ctgtgtatga tgatggtgct 11460 aggagagtgt ggacacttat gaatgtcttg acactcgttt ataaagttta ctatggcaac 11520 gctttagatc aagccatttc catgtgggct cttataatct ctgttacttc taactactca 11580 ggtgtagtta caactgtcat gtttttggcc agaggtattg tttttatgtg tgttgagtat 11640 tgccctattt tcttcataac tggtaataca cttcagtgta taatgctagt ctattgtttc 11700 ttaggctatt tttgtacttg ttacttcggc ctcttttgtt tactcaaccg ctactttaga 11760 ctgactcttg gtgtttatga ttacttagtg tctacacagg agtttagata tatgaattca 11820 cagggactac tcccacccaa gaatagcata gatgccttca aactcaacat taaattgttg 11880 ggtgttggtg gcaaaccttg tatcaaagta gccactgtac agtctaaaat gtcagatgta 11940 aagtgcacat cagtagtctt actctcagtt ttgcaacaac tcagagtaga atcatcatct 12000 aaattgtggg ctcaatgtgt ccagttacac aatgacattc tcttagctaa agatactact 12060 gaagcctttg aaaaaatggt ttcactactt tctgttttgc tttccatgca gggtgctgta 12120 gacataaaca agctttgtga agaaatgctg gacaacaggg caaccttaca agctatagcc 12180 tcagagttta gttcccttcc atcatatgca gcttttgcta ctgctcaaga agcttatgag 12240 caggctgttg ctaatggtga ttctgaagtt gttcttaaaa agttgaagaa gtctttgaat 12300 gtggctaaat ctgaatttga ccgtgatgca gccatgcaac gtaagttgga aaagatggct 12360 gatcaagcta tgacccaaat gtataaacag gctagatctg aggacaagag ggcaaaagtt 12420 actagtgcta tgcagacaat gcttttcact atgcttagaa agttggataa tgatgcactc 12480 aacaacatta tcaacaatgc aagagatggt tgtgttccct tgaacataat acctcttaca 12540 acagcagcca aactaatggt tgtcatacca gactacaaca catataagaa tacgtgtgat 12600 ggtacaacat ttacttatgc atcagcattg tgggaaatcc aacaggttgt agatgcagat 12660 agtaaaattg ttcagcttag tgaaattagt atggacaatt cacctaattt agcatggcct 12720 cttattgtaa cagctttaag ggccaattct gctgtcaaat tacagaataa tgagcttagt 12780 cctgttgcac taagacaaat gtcttgtgct gccggtacta cacaaactgc ttgcactgat 12840 gacaatgcgt tagcttacta caacacaaca aagggaggta ggtttgtact tgcactgtta 12900 tccgatttac aggatttgaa atgggctaga ttccctaaga gtgatggaac tggtactatc 12960 tatacagaac tggaaccacc ttgtaggttt gttacagaca cacctaaagg tcctaaagtg 13020 aagtatcttt acttcatcaa aggattaaac aacctaaata gaggtatggt acttggtagt 13080 ttagctgcca cagtacgttt acaagctggt aatgcaacag aagttcctgc taattcaact 13140 gtactttctt tctgtgcttt tgctgtagat gctgctaaag cttacaaaga ttatctagct 13200 agtgggggac aaccaatcac taattgtgtt aagatgttgt gtacacacac tggtactggt 13260 caggcaataa cagttacacc ggaagccaat atggatcaag aatcctttgg tggtgcatcg 13320 tgttgtctgt actgccgttg tcatatagat catccaaatc ctaaaggatt ttgtgactta 13380 aaaggtaagt atgtacaaat acctacaact tgtgctaatg accctgtggg ttttacactt 13440 aaaaacacag tctgtaccgt ctgcggtatg tggaaaggtt atggttgtag ttgtgatcaa 13500 ctccgcgaac ccatgcttca gtcagctgat gcacaatcgt ttttaaacgg gtttgcggtg 13560 taagtgcagc ccgtcttaca ccgtgcggca caggcactag tactgatgtc gtatatagag 13620 cttttgacat ctacaatgat aaagtagctg gttttgctaa gttcctaaaa actaattgtt 13680 gtcgcttcca agaaaaggac gaagatgaca atctcattga ttcttacttt gtagttaaga 13740 gacacacttt ctctaactac caacatgaag aaacaattta caacctgctt aaggattgtc 13800 cagctgttgc taaacatgac ttctttaagt ttagaataga cggtgacatg gtaccacata 13860 tatcacgtca acgtcttact aaatacacaa tggcagacct cgtctatgct ttaaggcatt 13920 ttgatgaagg taattgtgac acattaaaag aaatacttgt cacatacaat tgttgtgatg 13980 atgactactt caataaaaag gactggtatg attttgtaga aaacccagat atattacgcg 14040 tatacgccaa cttaggtgaa cgtgtacgcc aagctttgtt aaaaacagta cagttctgtg 14100 atgccatgcg aaatgctggt attgttggtg tactgacatt agataatcaa gatctcaatg 14160 gtaactggta tgactttggt gatttcatac aaaccacgcc aggtagtgga gttcctgttg 14220 tagactctta ttattcattg ctcatgccta tattaacctt gaccagggct ttaactgcag 14280 agtcacatgt tgacactgac ttaacaaagc cttacattaa gtgggatttg ttaaaatacg 14340 acttcacgga agagaggtta aaactctttg accgttattt taaatactgg gatcagacat 14400 accacccaaa ttgtgttaac tgtttggatg acagatgcat tctgcattgt gcaaacttta 14460 atgttctgtt ctctacagtg ttcccaccta caagttttgg accactagtg agaaaaatat 14520 ttgttgatgg tgttccattt gtagtttcaa ctggatacca cttcagagag ctaggtgttg 14580 tacataatca ggatgtaaac ttacatagct ctagacttag ttttaaggaa ttacttgtgt 14640 atgctgctga tcctgctatg catgctgctt ctggtaatct attactagat aaacgcacta 14700 cgtgcttttc agtagctgca cttactaaca atgttgcttt tcaaactgtc aaacccggta 14760 attttaacaa ggacttctat gactttgctg tgtctaaggg tttctttaag gaaggaagtt 14820 ctgttgaatt aaaacacttc ttctttgctc aggatggtaa tgctgctatc agcgattatg 14880 actactatcg ttataatcta ccaacaatgt gtgatatcag acaactacta tttgtagttg 14940 aagttgttga taagtacttt gattgttacg atggtggctg tattaatgct aaccaagtca 15000 tcgtcaacaa cctagacaaa tcagctggtt ttccatttaa taaatggggt aaggctagac 15060 tttattatga ttccatgagt tatgaggatc aagatgcact tttcgcatat acaaaacgta 15120 atgtcatccc tactataact caaatgaacc ttaagtatgc cattagtgca aagaatagag 15180 ctcgcaccgt agctggtgtc tctatctgta gtactatgac caatagacag tttcatcaaa 15240 aattactcaa gtcaatagcc gccactagag gagctactgt agtaattgga acaagcaaat 15300 tctatggtgg ttggcacaac atgctcaaaa ctgtttatag tgatgtagaa aaccctcacc 15360 ttatgggttg ggattatcct aaatgtgata gagccatgcc taacatgctt agaattatgg 15420 cctcacttgt tcttgctcgc aaacatacaa cgtgttgtag cttgtcacac cgtttctata 15480 gattagctaa tgagtgtgct caagtattga gtgaaatggt catgtgtggc ggttcactat 15540 atgttaaacc aggtggaacc tcatcaggag atgccacaac tgcttatgct aatagtgtgt 15600 ttaacatttg tcaagctgtc acggccaatg ttaatgcact tttatctact gatggtaaca 15660 aaattgccga taagtatgtc cgcaatttac aacacagact ttatgagtgt ctctatagaa 15720 atagagatgt tgacacagac tttgtgaatg agttttacgc atatttgcgt aaacatttct 15780 caatgatgat actctctgac gatgctgttg tgtgtttcaa tagcacttat gcatctcaag 15840 gtctagtggc tagcataaag aactttaagt cagttcttta ctatcaaaac aacgttttta 15900 tgtctgaagc aaaatgttgg actgagactg accttactaa aggacctcat gaattttgct 15960 ctcaacatac aatgctagtt aaacagggtg atgattatgt gtaccttcct tacccagatc 16020 catcaagaat cctaggtgcc ggttgttttg tagatgatat cgtaaaaaca gatggtacac 16080 ttatgattga acggttcgtg tctttagcta tagatgctta cccacttact aaacatccta 16140 atcaggagta tgctgatgtc tttcatttgt acttacaata catacgtaag ctacatgatg 16200 agttaacagg acacatgtta gacatgtatt ctgttatgct tactaatgat aacacttcaa 16260 ggtattggga acctgagttt tatgaggcta tgtacacacc gcatacagtc ttacaagctg 16320 ttggtgcttg tgttctttgc aattcacaga cttcattaag atgtggtgct tgcatacgta 16380 gaccattctt atgttgtaaa tgctgttacg accatgtcat ctcaacatca cataaattag 16440 tcttgtctgt taatccgtat gtttgcaatg ctccaggttg tgatgtcaca gatgtgactc 16500 aactttactt aggaggtatg agctattact gtaagtcaca taaaccaccc attagttttc 16560 cattgtgtgc taatggacaa gtttttggtc tctacaagaa tacatgtgtt ggtagcgata 16620 atgttactga ctttaatgca attgcaacat gtgactggac aaatgctggt gattacattt 16680 tagctaacac ctgtactgaa agactcaagc tttttgcagc agaaacgctc aaagctactg 16740 aggagacatt taaactgtct tatggtattg ctactgtacg tgaagtgctg tctgacagag 16800 aattacatct ttcatgggaa gttggtaaac ctagaccacc acttaaccga aattatgtct 16860 ttactggtta tcgtgtaact aaaaacagta aagtgcaaat cggagagtac acctttgaaa 16920 aaggtgacta tggtgatgct gttgtttacc gaggtacaac aacttacaaa ctcaacgttg 16980 gtgattattt tgtgctgaca tcacatacag taatgccatt aagtgcacct acactagtgc 17040 cacaagagca ctatgttaga attactggct tatacccaac actcaatatc tcagatgagt 17100 tttctagcaa tgttgcaaat tatcaaaagg ttggtatgca aaagtattct acactccagg 17160 gaccacctgg tactggtaaa agtcattttg ctattggtct agctctctac tacccttctg 17220 ctcgcatagt atatacagct tgctctcatg cagctgttga tgcactatgt gagaaggcat 17280 taaaatattt gcccatagac aaatgtagta gaattatacc tgcacgtgct cgtgtagagt 17340 gttttgataa attcaaggtg aattcaacat tagaacagta tgtcttttgt actgtaaatg 17400 cattgcctga gacgacagca gatatagttg tctttgatga aatttcaatg gccacaaatt 17460 atgatttgag tgttgtcaat gccagattac gtgctaagca ctatgtgtac attggtgatc 17520 ctgctcaatt acctgcacca cgcacattac taactaaggg tacactagaa ccagaatatt 17580 tcaattcagt gtgtagactt atgaaaacta taggtccaga catgttcctc ggaacttgtc 17640 gtagatgtcc tgctgaaatt gttgacactg tgagtgcttt ggtttatgat aataagctta 17700 aggcacataa agacaaatca gctcaatgct ttaaaatgtt ctacaagggt gttatcacgc 17760 atgatgtttc atctgcaatt aacaggccac aaataggcgt ggtaagagaa ttccttacac 17820 gtaaccctgc ttggagaaaa gctgtcttta tttcacctta caattcccag aatgctgtag 17880 cctcaaagat tttgggacta ccaactcaaa ctgttgattc atcacagggc tcagaatatg 17940 actatgtcat attcactcaa accactgaaa cagctcactc ttgtaatgta aacagattca 18000 acgttgctat taccagagca aaagtaggca tactttgcat aatgtctgat agagaccttt 18060 atgacaagtt gcaatttaca agtcttgaaa ttccacgtag gaatgtggca actttacaag 18120 ctgaaaatgt aacaggactc tttaaagatt gtagtaaggt aatcactggg ttacatccta 18180 cacaggcacc tacacactta agtgttgata ctaaattcaa aactgaaggt ttatgtgttg 18240 acatacctgg catacctaag gacatgacct atagaagatt aatctctatg atgggtttca 18300 aaatgaatta ccaggttaat ggttacccta acatgtttat cacccgcgaa gaagctataa 18360 gacatgtacg tgcatggatt ggcttcgatg tcgaaggttg tcatgctact agagaagctg 18420 ttggtaccaa tttaccttta cagctaggtt tttctacagg tgttaaccta gttgctgtac 18480 ctacaggtta tgttgataca cctaataata cagatttttc cagagttagt gctaaaccac 18540 cgcctggaga tcaatttaaa cacctcatac cacttatgta caaaggactt ccttggaatg 18600 tagtgcgtat aaagattgtc caaatgttaa gtgacacact taaaaatctc tctgacagag 18660 tcgtatttgt cttatgggca catggctttg agttgacatc tatgaagtat tttgtgaaga 18720 tcggacctga gcgcacatgt tgtctatgtg atagacgtgc tacatgcttt tccactgctt 18780 cagacactta tgcctgttgg catcattcta ttggatttga ttacgtctat aatccgttta 18840 tgattgatgt tcaacaatgg ggttttacag gtaacctaca aagcaaccat gatctgtatt 18900 gtcaagtcca tggtaatgca catgtagcta gttgtgatgc aatcatgact aggtgtctag 18960 ctgtccacga gtgctttgtt aagcgtgttg actggactat tgaatatcct ataatcggtg 19020 atgaactgaa gattaatgcg gcttgtagaa aggttcaaca catggttgtt aaagctgcat 19080 tattagcaga caaattccca gttcttcacg acattggtaa ccctaaagct attaagtgtg 19140 tacctcaagc tgatgtagaa tggaagttct atgatgcaca gccttgtagt gacaaagctt 19200 acaaaataga agaactgttc tattcttatg ccacacattc tgacaaattc acagatggtg 19260 tatgcctatt ttggaattgc aatgtcgata gatatcctgc taattccatt gtttgtagat 19320 ttgacactag agtgctatct aaccttaact tgcctggttg tgatggtggc agtttgtatg 19380 taaataagca tgcattccac acaccagctt ttgataaaag tgcttttgtt aatctaaagc 19440 aacttccatt tttctattac tctgacagtc catgtgagtc tcatggaaaa caagtagtgt 19500 cagatataga ttatgtacca ctaaagtctg ctacgtgtat aacacgttgc aatttaggtg 19560 gtgctgtctg tagacatcat gctaatgagt acagattgta tctcgatgct tataacatga 19620 tgatctcagc tggctttagc ttgtgggttt acaaacaatt tgatacctat aacctctgga 19680 acacttttac aagacttcag agtttagaaa atgtggcttt taatgttgta aataagggac 19740 actttgatgg acaacagggt gaagtaccag tttctatcat taacaacact gtttacacaa 19800 aagttgatgg tgttgatgta gaattgtttg agaacaaaac cacattacct gttaatgtag 19860 catttgagct ttgggctaag cgcaacatta aaccagtacc agaggtgaaa atactcaata 19920 atttgggtgt ggacattgct gctaatactg tgatctggga ctacaaaaga gatgctccag 19980 cacatatatc tactattggt gtttgttcta tgactgacat agccaagaaa ccaactgaaa 20040 cgatttgtgc accactcact gtcttttttg atggtagagt tgatggtcaa gtagacttat 20100 ttagaaatgc ccgtaatggt gttcttatta cagaaggtag tgttaaaggt ttacaaccat 20160 ctgtaggtcc caaacaagct agtcttaatg gagtcacatt aattggagaa gccgtaaaaa 20220 cacagttcaa ttattacaag aaagtggatg gtgttgtcca acaattacct gaaacttact 20280 ttactcagag tagaaactta caggaattta agcccaggag tcaaatggaa attgatttct 20340 tagaacttgc tatggatgaa ttcattgaac ggtataaatt agaaggctat gccttcgaac 20400 atatcgttta tggagatttt agtcatagtc agttaggtgg tttacatcta ctgattggac 20460 tagctaaacg ttttaaggaa tcaccttttg aacttgaaga ttttattcct atggacagta 20520 cagttaaaaa ctacttcata acagatgcgc aaacaggttc atctaagtgt gtgtgttctg 20580 ttattgatct tttacttgat gacttcgttg aaataataaa gtcccaagat ttatctgtag 20640 tttctaaggt tgtcaaagtg actattgact atacagaaat ctcatttatg ctttggtgta 20700 aagatggcca tgtagaaaca ttttacccaa aattacaatc tagtcaagcg tggcaaccgg 20760 gtgttgctat gcctaatctt tacaaaatgc aaagaatgct attagaaaag tgtgaccttc 20820 aaaattatgg tgatagtgca acattaccta aaggcataat gatgaatgtc gcaaaatata 20880 ctcaactgtg tcaatattta aacacactga cattagctgt accctataat atgagagtta 20940 tccattttgg tgctggttct gataaaggag ttgcaccagg tacagctgtt ttaagacaat 21000 ggttgcctac aggtacgctg cttgtcgatt cagatcttaa tgactttgtc tctgatgcag 21060 attcaacttt gattggtgat tgtgcaactg tacatacagc taataaatgg gatctcatta 21120 ttagtgatat gtacgaccct aagactaaga atgtcacaaa agaaaacgac tctaaagagg 21180 gttttttcac ttacatttgt gggtttatac aacaaaagct agctcttgga ggttccgtgg 21240 ctataaagat aacagaacat tcttggaatg ctgatcttta taagctcatg ggacacttcg 21300 catggtggac agcctttgtt actaatgtga atgcgtcatc atctgaagca tttttaatcg 21360 gatgtaacta ccttggcaaa ccacgcgaac aaatagatgg ttatgtcatg catgcaaatt 21420 acatattttg gaggaataca aatccaattc agctttcttc ttattcttta ttcgacatga 21480 gtaaattccc ccttaaatta aggggtactg ctgttatgtc tttaaaagaa ggtcaaatca 21540 atgatatgat tctctctctt cttagtaaag gtagacttat aattagagaa aacaacagag 21600 ttgttatttc tagtgatgtt cttgttaaca actaaacgaa caatgtttgt ttttcttgtt 21660 ttattgccac tagtctctag tcagtgtgtt aatcttacaa ccagaactca attaccccct 21720 gcatacacta attctttcac acgtggtgtt tattaccctg acaaagtttt cagatcctca 21780 gttttacatt caactcagga cttgttctta cctttctttt ccaatgttac ttggttccat 21840 gctatacatg tctctgggac caatggtact aagaggtttg ataaccctgt cctaccattt 21900 aatgatggtg tttactttgc ttccactgag aagtctaaca taataagagg ctggattttt 21960 ggtactactt tagattcgaa aacccagtcc ctacttattg ttaataacgc tactaatgtt 22020 gttatcaaag tctgtgaatt tcaattttgt aacgatccat ttttgggtgt ttattaccac 22080 aaaaacaaca aaagttggat ggaaagtgag ttcagagttt attctagtgc gaataattgc 22140 acttttgaat acgtctctca gccttttctt atggaccttg aaggaaaaca gggtaatttc 22200 aaaaatctta gggaatttgt gttcaagaat attgatggtt acttcaagat atactctaag 22260 cacacgccta ttaatttagt gcgtgatctc cctcagggtt tttcggcttt agaaccattg 22320 gtagatttgc caataggtat taacatcact aggtttcaaa ctttacttgc tttacataga 22380 agttatttaa ctcctggtga ttcttcttca ggttggacag ctggtgctgc agcttattat 22440 gtgggttatc ttcaacctag gacttttcta ctgaagtaca atgaaaatgg aaccattaca 22500 gatgctgtag actgtgcact tgaccctctc tcagaaacaa agtgtacgtt gaaatccttc 22560 actgtagaaa aaggaatcta tcaaacttct aactttagag tccaaccaac agaatctatt 22620 gttagatttc ctaacatcac aaacttgtgc ccttttggtg aagtttttaa cgccaccaga 22680 tttgcatctg tttatgcttg gaacaggaag agaatcagca actgtgttgc tgattattct 22740 gtcctgtata attccgcatc attttccact tttaagtgtt atggagtgtc tcctactaaa 22800 ttaaatgatc tctgctttac taatgtctat gcagattcat ttgtaattag aggtgatgaa 22860 gtcagacaaa tcgctccagg gcaaactgga aagattgctg attataacta caaattacca 22920 gatgatttta caggctgcgt tatagcttgg aattctaaca atcttgattc taaggttggt 22980 ggtaattata attacctgta cagattgttt aggaagtcta atctcaaacc ttttgagaga 23040 gatatttcaa ctgaaatcta tcaggccggt agcacacctt gtaatggtgt tgaaggtttt 23100 aattgttact ttcctctgca atcatatggt ttccaaccca ctaatggtgt tggttaccaa 23160 ccatacagag tagtagtact ttcttttgaa cttctacatg caccagcaac tgtttgtgga 23220 cctaaaaagt ctactaattt ggttaagaac aagtgtgtca atttcaactt caatggttta 23280 acaggcacag gtgttcttac tgagtctaac aaaaagtttc tgcctttcca acaatttggc 23340 agagacattg ctgacactac tgatgctgtt cgtgatccac aaacacttga gattcttgac 23400 attacaccat gttcttttgg tggtgtcagt gttataacac caggaacaaa tacttctaac 23460 caggttgctg ttctttatca ggatgttaac tgcacagaag tccctgttgc tattcatgca 23520 gatcaactta ctcctacttg gcgtgtttat tctacaggtt ctaatgtttt tcaaacacgt 23580 gcaggctgtt taataggggc tgaacatgtc aacaactcat atgagtgtga catacccatt 23640 ggtgcaggta tatgcgctag ttatcagact cagactaatt ctcctcggag agcaagaagt 23700 gtagctagtc aatccatcat tgcctacact atgtcacttg gtgcagaaaa ttcagttgct 23760 tactctaata actctattgc catacccaca aattttacta ttagcgttac cacagaaatt 23820 ctaccagtgt ctatgaccaa gacatcagta gattgtacaa tgtacatttg tggtgattca 23880 actgaatgca gcaatctttt gttgcaatat ggcagttttt gtacacaatt aaaccgtgct 23940 ttaactggaa tagctgttga acaagacaaa aacacccaag aagtttttgc acaagtcaaa 24000 caaatttaca agacaccacc aattaaagat tttggcggtt ttaattttag ccagatactg 24060 ccagatccat caaaaccaag caagaggtca tttattgaag atctactgtt caacaaagtg 24120 acacttgcag atgctggctt catcaaacaa tatggtgatt gccttggtga tattgctgct 24180 agagacctca tttgtgcaca aaagtttaac ggccttactg ttttgccacc tttgctcaca 24240 gatgaaatga ttgctcaata cacttctgca ctgttagcag gtacaatcac ttctggttgg 24300 acttttggtg caggtgctgc attacaaata ccatttgcta tgcaaatggc ttataggttt 24360 aatggtattg gagttacaca gaatgttctc tatgagaacc aaaaattgat tgccaaccaa 24420 tttaatagtg ctattggcaa aattcaagac tcactttctt ccacagcaag tgcacttgga 24480 aaacttcaag atgtggtcaa ccaaaatgca caagctttaa acacgcttgt taaacaactt 24540 agctccaatt ttggtgcaat ttcaagtgtt ttaaacgaca tcctttcacg tcttgacaaa 24600 gttgaggctg aagtgcaaat tgataggttg atcacaggca gacttcaaag tttgcagaca 24660 tatgtgactc aacaattaat tagagctgca gaaatcagag cttctgctaa tcttgctgct 24720 actaaaatgt cagagtgtgt acttggacaa tcaaaaagag ttgacttttg cggaaagggc 24780 tatcatctta tgtcatttcc tcagtcagca cctcatggtg tcgtcttttt gcatgtgact 24840 tatgtccctg cacaagaaaa gaacttcaca actgctcctg ccatttgtca tgatggaaaa 24900 gcacactttc ctcgtgaagg tgtctttgtt tcaaatggca cacactggtt tgtaacacaa 24960 aggaattttt atgaaccaca aatcattact acagacaaca catttgtgtc tggtaactgt 25020 gatgttgtaa taggaattgt caacaacaca gtttatgatc ctttgcaacc tgaattagac 25080 tcattcaagg aggagcttga taaatacttc aagaaccata cctcaccaga tgttgattta 25140 ggtgacatct ctggcattaa tgcttcagtt gtaaacattc agaaagaaat cgaccgcctc 25200 aatgaggttg ccaagaattt aaatgaatct ctcatcgatc tccaagaact tggaaagtat 25260 gagcagtata taaaatggcc atggtacatt tggctaggtt ttatagctgg cttgattgcc 25320 atagtaatgg tgacaattat gctttgctgt atgaccagtt gctgtagttg tctcaagggc 25380 tgttgttctt gtggatcctg ctgcaaattt gacgaggacg actctgagcc agtgctcaaa 25440 ggagtcaaat tacattacac ataaacgaac ttatggattt gtttatgaga atcttcacaa 25500 ttggaactgt aactttgaag caaggtgaaa tcaaggatgc tactccttca gattttgtta 25560 gagctactgc aacgataccg atacaagcat cacttccttt cggatggctt attgttggcg 25620 ttgcacttct tgctgttttt cagagcgctt ccaaaatcat aaccctcaaa aagagatggc 25680 aactagcact ctccaagggt gttcactttg tttgcaactt gctgttgttg tttgtaacag 25740 tttactcaca tcttttgctt gttgctgctg gccttgaagc cccttttctc tatctttatg 25800 ctttagtcta cttcttgcag agtataaact ttgtacgcat aataatgagg ctttggcttt 25860 gctggaaatg ccgttccaaa aacccattac tttatgatgc caactatttt ctttgctggc 25920 atactaattg ttacgactat tgtatacctt acaatagtgt aacttcttca attgtcatta 25980 cttcaggtga tggcacaaca agtcctattt ctgaacatga ctaccagatt ggtggttata 26040 ctgaaaaatg ggaatctgga gtaaaagact gtgttgtatt acacagttac ttcacttcag 26100 actattacca gctgtactca actcaattga gtacagacac tggtgttgaa catgttacct 26160 tcttcatcta caataaaatc gttgatgagc ctgaagaaca tgtccaaatt cacacaatcg 26220 acgtttcatc cggagttgtt aatccagtaa tggaaccaat ttatgatgaa ccgacgacga 26280 ctactagcgt gcctttgtaa gcacaagctg atgagtacga acttatgtac tcattcgttt 26340 cggaagagac aggtacgtta atagttaata gcgtacttct ttttcttgct ttcgtggtat 26400 tcttgctagt tacactagcc attcttactg cgcttcgatt gtgtgcgtac tgttgcaata 26460 ttgttaacgt gagtcttgta aaaccttctt tttacgttta ctctcgtgtt aaaaatctga 26520 attcttctcg ggttcctgat cttctggtct aaacgaacta aatattatat tagtttttct 26580 gtttggaact ttaattttag ccatggcaga ttccaacggt actattaccg ttgaggagct 26640 gaaaaagctc cttgaacaat ggaacctagt aataggtttc ctattcctta catggatttg 26700 cctgctgcaa tttgcctatg ccaacaggaa taggtttttg tacatcatta agttgatttt 26760 cctctggctg ttatggccag taactttagc ttgttttgtg cttgctgctg tttacagaat 26820 aaattggatc accggtggaa ttgctattgc aatggcttgt cttgtaggat tgatgtggct 26880 aagctacttc attgcttctt tcagactgtt tgcgcgtacg cgttccatgt ggtcattcaa 26940 tccagaaact aacattcttc tcaacgtgcc actccatgga actattctga ctagaccgct 27000 tctagaaagt gaactcgtaa tcggagctgt tatccttcgt ggacatcttc gtattgctgg 27060 acatcatcta ggacgctgtg acatcaagga tctacctaaa gaaatcactg ttgctacatc 27120 acgaacgctt tcttattaca aattgggagc ttcacagcgt gtagcaggtg attcaggttt 27180 tgctgcatat agtcgctaca ggattggcaa ctataaatta aacacagacc attccagtag 27240 cagtgacaat attgctttgc ttgtacagta agtgacaaca gatgtttcat ctcgttgact 27300 ttcaggttac tatagcagag atattactaa tcatcatgag gacttttaaa gtttccattt 27360 ggaatcttga ttacatcata aacctcataa ttaagaactt aagcaagtca ctaactgaga 27420 ataaatattc tcaactagac gaggagcagc caatggagat tgattaaacg aacatgaaaa 27480 ttattctttt cttggcactg ataacactcg ctacttgtga gctttatcac taccaagagt 27540 gtgttagagg tacaacagta cttttaaaag aaccttgctc gtcgggaaca tacgagggca 27600 attcaccatt tcatcctcta gctgataaca aatttgcact gacttgcttt agcactcaat 27660 ttgcttttgc ttgtcctgac ggcgtaaaac acgtctatca gttacgtgcc agatcagttt 27720 cacctaaact gttcatcaga caagaggaag ttcaagaact ttactctcca atttttctta 27780 ttgttgcggc aatagtgttt ataacacttt gcttcacact caaaagaaag acagaatgat 27840 tgaactttca ttaattgact tctatttgtg ctttttagcc tttctgctat tccttgtttt 27900 aattatgctt attatctttt ggttctcact tgaactgcaa gatcataatg aaacttgtca 27960 cgcctaaacg aacatgaaat ttcttgtttt cttaggaatc atcacaactg tagctgcatt 28020 tcaccaagaa tgtagtttac agtcatgtac tcaacatcaa ccatatgtag ttgatgaccc 28080 gtgtcctatt cacttctatt ctaaatggta tatcagagta ggagctagaa aatcagcacc 28140 tttaattgaa ttgtgcgtgg atgaggctgg ttctaaatca cccattcagt acatcgatat 28200 cggtaattat acagtttcct gtttaccttt tacaattaac tgccaggaac ctaaattggg 28260 tagtcttgta gtgcgttgtt cgttctacga ggacttttta gagtatcatg acgttcgtgt 28320 tgttttagat ttcatctaaa cgaacaaact aaaatgtctg ataatggacc tcaaaatcag 28380 cgaaatgcac ctcgcattac gtttggtgga ccatcagatt caactggcag taaccagaat 28440 ggagaacgaa gtggtgcgcg atcaaaacaa cgccgcccgc aaggtttacc caataatact 28500 gcgtcttggt tcaccgctct cactcaacat ggcaaggaag atttaaaatt ccctcgagga 28560 caaggcgttc caattaacac caatagcagt ccagatgacc aaattggcta ctaccgccgc 28620 gccacaagac gaattcgtgg tggtgatggt aaaatgaaag atctcagtcc aagatggtat 28680 ttctactatc taggaactgg gccagaagct ggacttcctt atggtgctaa caaagatggc 28740 atcatatggg ttgcaactga gggagccttg aatacaccaa aagatcacat tggcaccaga 28800 aatcctgcta acaatgctgc aatcgtgcta caacttcctc aaggaacaac attaccaaaa 28860 ggtttttacg cagaagggtc tagaggtgga agtcaagcct cttctagatc atcatcacgt 28920 agtcgcaaca gttcaagaaa ttcaactcca ggttcaagta gaggaacttc tcctgctaga 28980 atggctggaa atggaggtga tgctgctctt gctttgttac tacttgacag attgaaccag 29040 cttgagagca aaatgtctgg taaaggccaa caacaacaag gccaaactgt cactaagaaa 29100 tctgctgctg aggcttctaa gaagcctaga caaaaacgta ctgccactaa agcatacaat 29160 gtaacacaag ctttcggcag acgtggtcca gaacaaactc aaggaaattt tggggatcag 29220 gaactaatca gacaaggaac tgattacaaa cattggccgc aaattgcaca atttgctcct 29280 tctgcttcag cgttctttgg aatgtcgaga attggaatgg aagtcacacc ttcgggaaca 29340 tggttgacct atacaggtgc catcaaattg gatgacaaag atccaaattt caaagatcaa 29400 gtcattttgc tgaataagca tattgacgca tacaaaacat tcccaccaac agagcctaaa 29460 aaggacaaaa agaagaaggc tgatgaaact caagccttac cgcagagaca gaagaaacag 29520 caaactgtga ctcttcttcc tgctgcagat ttggatgatt tctccaaaca attgcaacaa 29580 tccatgagca gtgctgactc aactcaggcc taaactcatg cagaccacac aaggcagatg 29640 ggctatataa acgttttcgc ttttccgttt acgatatata gtctactctt gtgcagaatg 29700 aattctcgta actacatagc acaagtagat gtagttaact ttaatctcac atagcaatct 29760 ttaatcagtg tgtaacatta gggaggactt gaaagagcca ccacattttc accgaggcca 29820 cgcggagtac gatcgagtgt acagtgaaca atgctaggga gagctgccta tatggaagag 29880 ccctaatgtg taaaattaat tttagtagtg ctatccccat gtgattttaa tagcttctta 29940 ggagaatgac aaaaaaaaac aaaaaaaa 29968 <210> 45 <211> 10827 <212> DNA <213> Artificial Sequence <220> <223> vector <400> 45 cggccgtaag atacattgat gagtttggac aaaccacaac tagaatgcag tgaaaaaaat 60 gctttatttg tgaaatttgt gatgctatag ctttatttgt aaccattata agctgcaata 120 aacaagttgt ttaaaccacg tgatgaccat acacctcggg atactagatg tataatgtcc 180 gccatgcaga cgaaaccagt cggagattac cgagcattct atcacgtcgg cgaccaatag 240 tgagcttagg gataacaggg taataaacga tccccgggaa ttcactggcc gtcgttttac 300 aacgtcgtga ctgggaaaac cctggcgtta cccaacttaa tcgccttgca gcacatcccc 360 ctttcgccag ctggcgtaat agcgaagagg cccgcaccga tcgcccttcc caacagttgc 420 gcagcctgaa tggcgaatgg cgatagatcc ggtggatgac cttttgaatg acctttaata 480 gattatatta ctaattaatt ggggacccta gaggtcccct tttttatttt aaaaattttt 540 tcacaaaacg gtttacaagc ataaagctcg gacggatctt ttccgctgca taaccctgct 600 tcggggtcat tatagcgatt ttttcggtat atccatcctt tttcgcacga tatacaggat 660 tttgccaaag ggttcgtgta gactttcctt ggtgtatcca acggcgtcag ccgggcagga 720 taggtgaagt aggcccaccc gcgagcgggt gttccttctt cactgtccct tattcgcacc 780 tggcggtgct caacgggaat cctgctctgc gaggctggcc ggctaccgcc ggcgtaacag 840 atgagggcaa gcggatggct gatgaaacca agccaaccag gaagggcagc ccacctatca 900 aggtgtcgat gcaggggggg gggaaagcca cgttgtgtct caaaatctct gatgttacat 960 tgcacaagat aaaaatatat catcatgaac aataaaactg tctgcttaca taaacagtaa 1020 tacaaggggt gttatgagcc atattcaacg ggaaacgtct tgctcaaggc cgcgattaaa 1080 ttccaacatg gatgctgatt tatatgggta taaatgggct cgcgataatg tcgggcaatc 1140 aggtgcgaca atctatcgat tgtatgggaa gcccgatgcg ccagagttgt ttctgaaaca 1200 tggcaaaggt agcgttgcca atgatgttac agatgagatg gtcagactaa actggctgac 1260 ggaatttatg cctcttccga ccatcaagca ttttatccgt actcctgatg atgcatggtt 1320 actcaccact gcgatccccg gaaaaacagc attccaggta ttagaagaat atcctgattc 1380 aggtgaaaat attgttgatg cgctggcagt gttcctgcgc cggttgcatt cgattcctgt 1440 ttgtaattgt ccttttaaca gcgatcgcgt atttcgtctc gctcaggcgc aatcacgaat 1500 gaataacggt ttggttgatg cgagtgattt tgatgacgag cgtaatggct ggcctgttga 1560 acaagtctgg aaagaaatgc ataagttttt gccattctca ccggattcag tcgtcactca 1620 tggtgatttc tcacttgata accttatttt tgacgagggg aaattaatag gttgtattga 1680 tgttggacga gtcggaatcg cagaccgata ccaggatctt gccatcctat ggaactgcct 1740 cggtgagttt tctccttcat tacagaaacg gctttttcaa aaatatggta ttgataatcc 1800 tgatatgaat aaattgcagt ttcatttgat gctcgatgag tttttctaat cagaattggt 1860 taattggttg taacactggc agagcattac gctgacttga cgggacggcg gctttgttga 1920 ataaatcgaa cttttgctga gttgaaggat cagatcacgc atcttcccga caacgcagac 1980 cgttccgtgg caaagcaaaa gttcaaaatc accaactggt ccacctacaa caaagctctc 2040 atcaaccgtg gctccctcac tttctggctg gatgatgggg cgattcaggc ctggtatgag 2100 tcagcaacac cttcttcacg aggcagacct cagacggtat cggatcgatc ccccgatgtg 2160 tagcagtggc ggaccatata ggcagatcag aaggcgcggt tctcctacat gagcttttca 2220 attcaattca tcattttttt tttattcttt tttttgattt cggtttcctt gaaatttttt 2280 tgattcggta atctccgaac agaaggaaga acgaaggaag gagcacagac ttagattggt 2340 atatatacgc atatgtagtg ttgaagaaac atgaaattgc ccagtattct taacccaact 2400 gcacagaaca aaaacctgca ggaaacgaag ataaatcatg tcgaaagcta catataagga 2460 acgtgctgct actcatccta gtcctgttgc tgccaagcta tttaatatca tgcacgaaaa 2520 gcaaacaaac ttgtgtgctt cattggatgt tcgtaccacc aaggaattac tggagttagt 2580 tgaagcatta ggtcccaaaa tttgtttact aaaaacacat gtggatatct tgactgattt 2640 ttccatggag ggcacagtta agccgctaaa ggcattatcc gccaagtaca attttttact 2700 cttcgaagac agaaaatttg ctgacattgg taatacagtc aaattgcagt actctgcggg 2760 tgtatacaga atagcagaat gggcagacat tacgaatgca cacggtgtgg tgggcccagg 2820 tattgttagc ggtttgaagc aggcggcaga agaagtaaca aaggaaccta gaggcctttt 2880 gatgttagca gaattgtcat gcaagggctc cctatctact ggagaatata ctaagggtac 2940 tgttgacatt gcgaagagcg acaaagattt tgttatcggc tttattgctc aaagagacat 3000 gggtggaaga gatgaaggtt acgattggtt gattatgaca cccggtgtgg gtttagatga 3060 caagggagac gcattgggtc aacagtatag aaccgtggat gatgtggtct ctacaggatc 3120 tgacattatt attgttggaa gaggactatt tgcaaaggga agggatgcta aggtagaggg 3180 tgaacgttac agaaaagcag gctgggaagc atatttgaga agatgcggcc agcaaaacta 3240 aaaaactgta ttataagtaa atgcatgtat actaaactca caaattagag cttcaattta 3300 attatatcag ttattacccg ggaatctcgg tcgtaatgat ttttataatg acgaaaaaaa 3360 aaaaattgga aagaaaaagc tgggcgcgcc ggccggccct tttcatcacg tgctataaaa 3420 ataattataa tttaaatttt ttaatataaa tatataaatt aaaaatagaa agtaaaaaaa 3480 gaaattaaag aaaaaatagt ttttgttttc cgaagatgta aaagactcta gggggatcgc 3540 caacaaatac taccttttat cttgctcttc ctgctctcag gtattaatgc cgaattgttt 3600 catcttgtct gtgtagaaga ccacacacga aaatcctgtg attttacatt ttacttatcg 3660 ttaatcgaat gtatatctat ttaatctgct tttcttgtct aataaatata tatgtaaagt 3720 acgctttttg ttgaaatttt ttaaaccttt gtttattttt ttttttcttc attccgtaac 3780 tcttctacct tctttattta ctttctaaaa tccaaataca aaacataaaa ataaataaac 3840 acagagtaaa ttcccaaatt attccatcat taaaagatac gaggcgcgtg taagttacag 3900 gcaagcgatc ggccggcccg ggcatttaaa tgcaggccgc gtacgcgtcg acggtaccga 3960 attcgcttaa acgagctcat gttcgccggt gaacgcgttg aggaagccgg gcagtgcctc 4020 ggcaaaatcc ttgcgtgtag acaagacatc tgcgtagcag ttgtcctcaa caacgatgtc 4080 gaaatccaaa tcggagtgct catcgagtcc tccgtgaacg taagagccgc cgatcagaag 4140 agcgcggaag cgaacatcgg aagcgaccgc atcgcggatg cggttcaaga aagttgcatg 4200 agcttgtgga agtgtgctga gcataaatga ttctcctagc tgttctttgg gtaagtacgc 4260 catcaggacg ttgtgagtgg cgcgattttt agcggctgaa atcagccctt gagcctgtcg 4320 gcaagtcgcg tcatgaggtc catgcgctca tgcaggatcg ccacgaccaa cgcgggttcg 4380 cccgcacgcg gcaggcaaaa aacgtagtgg tgttcgcagc gggccatccg cagcgcggga 4440 aagagttcgc tcatgtcctt aaacgggcct tcgccggcgg caagcctggc tatgccctgt 4500 tccagcttag cgatatagcg gcgcacctgc gccgcgcccc actcccggcg cgtgtagcgg 4560 atgatgccgc gtagatcggc ttcggcctca gccgtgagga tgtaggccgt caagcgcgat 4620 ccccgctgag ttcttcatca agaatttcgc cgacgctctt ggtggacacc ttgccggcaa 4680 gcccatcgtt gatgcggttc cccagcatgg ttttcagttc ctgccatgcc tgatcggcat 4740 cagcgtcacc ggggaacaga cgttcgaggg cgtattgctt aatggtcttg ccctgcaagg 4800 cggccagggc tttcaggctc tggtgctgct ggtccgtcat gtcgattgtc aggcggctca 4860 ttggataacc tccataaaat acacgtaacc acattagcac atatgtgggc gtgaggctac 4920 agcgcgaggc gcattaaggt cgggaaaatg cgctaggcgc atttaaattg cgtattgctg 4980 taatgcgcca tgccggctag actaggccca aatgggtata cccaatttga ccaaggggga 5040 cgcgatgagg gcggccaagc actaccgaca acttctatcc atcgacttca acatcgaggc 5100 gctggccttc gtgcctggac ccgacggcac acgcggccgg cgcatccacg tcctggggcg 5160 cgaggtccgc gaccggcccg gcctggtcga gtacctttcg ccggcgttcg gctcgcgggt 5220 ggcgctggac ggctactgca aggccaattt cgatgcagtg ctgcacctgg cgtaccccga 5280 tcatcagcaa tggggccacg catgaagcgc cgaagctacg ccatgctgcg cgccgctgcc 5340 gcgctggccg tcctggtcgt tgcctcgccg gcatgggccg agctgcgcgg cgaggtcgtg 5400 cgcatcatcg acggcgacac catcgacgtg ctggtagaca agcagccggt gcgcgtgcgc 5460 ctggtggaca ttgacgcgcc ggaaaagcgg caagccttcg gcgaacgtgc gcgccaggcg 5520 ctggccggca tggtgttccg ccggcacgtc ctggtcgacg agaaggacac cgaccgttac 5580 ggccgcacgc tgggcaccgt gtgggtcaac atggagctgg ccagccggcc gccgcagccg 5640 cgcaacgtca acgccgcgat ggttcaccag ggcatggcgt gggcctatcg cttccacggc 5700 cgcgcggccg accctgaaat gctgcggctc gaacaggagg cgcgaggcaa gcgcgtcggc 5760 ctctggtccg atccgcacgc cgtcgagccg tggaaatggc gacgcgagag caacaaccgg 5820 agggacgaag gttgaaggtc gcccgcatct acctgcgcgc cagtacggac gagcagaatc 5880 ttgaacgcca ggagagcctt gtagcggcca cgcgggccgc cgggtactac gtcgccggca 5940 tctaccgcga gaaggcgtcc ggcgcacgcg ccgaccggcc cgagctgctg cgcatgatcg 6000 cggacctgca acctggtgaa gtcgtcgttg cggagaagat cgaccgcatc agccgcttgc 6060 cgttggccga ggccgagcgc ctggttgcgt cgatccgggc caaaggggcc aagctggccg 6120 tgcctggcgt ggtggacctg tcggagctgg ccgccgaggc gaacggagtg gcgaaaatcg 6180 ttctggaatc cgtccaggac atgcttttga agctcgcctt gcagatggcc cgcgacgact 6240 acgaggatcg gcgcgagcgt caacgtcagg gtgtccagtt ggcgaaggcc gccggccgct 6300 acaccggccg caaacgtgac gccggcatgc acgaccgcat catcacgctt cgctccggcg 6360 gatcgagcat tgccaagacg gccaagctgg tcggatgcag cccgagccag gtcaaacgag 6420 tgtgggcggc ctggaacgcg cagcagcaaa aataaagccg ggcagtgccc ggcttttctc 6480 accttttcgc gtcccgcagg gccgctgcga gcgccctacc tagatcctcg ctttccccct 6540 cggtgtagtc cggccagggc acgaagggcg cggatgcgaa cctgttgagc aggtacgcct 6600 tcgggcagcg gtagaccacc ggcgagttcg ccttttcatc ccaccgggcc aggatcacgt 6660 ccgcatcaca gtgcatgtcc ttcacctggt cgcggaagaa gccgaaggcc accatgccgc 6720 tatgttcgcc gaggaacgcc agttgcttcg cgctggcgat cgcgccgacg ccgccggcca 6780 aaaccgacgc catcacccag ccgacgaacc agaagctggc atgcttgcgg ttgaccaccg 6840 cacgcgcagc cgcgaccagg acaacggcca agctgccgac cagggccatg acgaccgtga 6900 tccggccgtt gtggaaagcg atgggcttgc cagcgtccgc ttgcacggcg tcgtaaatgc 6960 tggacccgat gggcgcgcac atcagcacga caggcagcag caccaggaac atcgtccgcg 7020 tccattgcgc gagtgccttg cggcgttcgc cggcggcaag cgcctccatc atcggcgtga 7080 agcccaacag ggccaccgca gccgccaagc cggcaacgat gccgcaggcg attacataca 7140 tacatcctcc ctaatgcgcc ttgcgcacgg ttgtagtcag agtccgcggt ggggcgataa 7200 gctcatgacc aaaatccctt aacgtgagtt ttcgttccac tgagcgtcag accccgtaga 7260 aaagatcaaa ggatcttctt gagatccttt ttttctgcgg gggatcagga ccgctgccgg 7320 agcgcaaccc actcactaca gcagagccat gtagacaaca tcccctcccc ctttccaccg 7380 cgtcagacgc ccgtagcagc ccgctacggg ctttttcatg ccctgcccta gcgtccaagc 7440 ctcacggccg cgctcggcct ctctggcggc cttctggcgc tcctgctgcg gcgtccgctc 7500 gtgggccgtg gcgcgggtcc gcgcgccggc ctcgtgcgcc tggcgctcgc gggcgaggtc 7560 cagggcggcc gtcttcacgt tctgccttgc gcagatgaga tagatcgatc tagcgtggac 7620 tcaaggctct cgcgaatggc tcgcgttgga aactttcatt gacacttgag gggcaccgca 7680 gggaaattct cgtccttgcg agaaccggct atgtcgtgct gcgcatcgag cctgcgccct 7740 tggcttgtct cgcccctctc cgcgtcgcta cggggcttcc agcgcctttc cgacgctcac 7800 cgggctggtt gccctcgccg ctgggctggc ggccgtctat ggccctgcaa acgcgccaga 7860 aacgccgtcg aagccgtgtg cgagacaccg cggccgccgg cgttgtggat acctcgcgga 7920 aaacttggcc ctcactgaca gatgaggggc ggacgttgac acttgagggg ccgactcacc 7980 cggcgcggcg ttgacagatg aggggcaggc tcgatttcgg ccggcgacgt ggagctggcc 8040 agcctcgcaa atcggcgaaa acgcctgatt ttacgcgagt ttcccacaga tgatgtggac 8100 aagcctgggg ataagtgccc tgcggtattg acacttgagg ggcgcgacta ctgacagatg 8160 aggggcgcga tccttgacac ttgaggggca gagtgctgac agatgagggg cgcacctatt 8220 gacatttgag gggctgtcca caggcagaaa atccagcatt tgcaagggtt tccgcccgtt 8280 tttcggccac cgctaacctg tcttttaacc tgcttttaaa ccaatattta taaaccttgt 8340 ttttaaccag ggctgcgccc tgtgcgcgtg accgcgcacg ccgaaggggg gtgccccccc 8400 ttctcgaacc ctcccggccc gctaacgcgg gcctcccatc cccccagggg ctgcgcccct 8460 cggccgcgaa cggcctcacc ccaaaaatgg cagcgctggc agtccttgcc attgccggga 8520 tcggggcagt aacgggatgg gcgatcagcc cgagcgcgac gcccggaagc attgacgtgc 8580 cgcaggtgct ggcatcgaca ttcagcgacc aggtgccggg cagtgagggc ggcggcctgg 8640 gtggcggcct gcccttcact tcggccgtcg gggcattcac ggacttcatg gcggggccgg 8700 caatttttac cttgggcatt cttggcatag tggtcgcggg tgccgtgctc gtgttcgggg 8760 gtgaattaat tccccggatc gatccgtcag cttcacgctg ccgcaagcac tcagggcgca 8820 agggctgcta aaggaagcgg aacacgtaga aagccagtcc gcagaaacgg tgctgacccc 8880 ggatgaatgt cagctactgg gctatctgga caagggaaaa cgcaagcgca aagagaaagc 8940 aggtagcttg cagtgggctt acatggcgat agctagactg ggcggtttta tggacagcaa 9000 gcgaaccgga attgccagct ggggcgccct ctggtaaggt tgggaagccc tgcaaagtaa 9060 actggatggc tttcttgccg ccaaggatct gatggcgcag gggatcaaga tcgacggatc 9120 gatccgggga attaattccg gggcaatccc gcaaggaggg tgaatgaatc ggacgtttga 9180 ccggaaggca tacaggcaag aactgatcga cgcggggttt tccgccgagg atgccgaaac 9240 catcgcaagc cgcaccgtca tgcgtgcgcc ccgcgaaacc ttccagtccg tcggctcgat 9300 ggtccagcaa gctacggcca agatcgagcg cgacagcgtg caactggctc cccctgccct 9360 gcccgcgcca tcggccgccg tggagcgttc gcgtcgtctc gaacaggagg cggcaggttt 9420 ggcgaagtcg atgaccatcg acacgcgagg aactatgacg accaagaagc gaaaaaccgc 9480 cggcgaggac ctggcaaaac aggtcagcga ggccaagcag gccgcgttgc tgaaacacac 9540 gaagcagcag atcaaggaaa tgcagctttc cttgttcgat attgcgccgt ggccggacac 9600 gatgcgagcg atgccaaacg acacggcccg ctctgccctg ttcaccacgc gcaacaagaa 9660 aatcccgcgc gaggcgctgc aaaacaaggt cattttccac gtcaacaagg acgtgaagat 9720 cacctacacc ggcgtcgagc tgcgggccga cgatgacgaa ctggtgtggc agcaggtgtt 9780 ggagtacgcg aagcgcaccc ctatcggcga gccgatcacc ttcacgttct acgagctttg 9840 ccaggacctg ggctggtcga tcaatggccg gtattacacg aaggccgagg aatgcctgtc 9900 gcgcctacag gcgacggcga tgggcttcac gtccgaccgc gttgggcacc tggaatcggt 9960 gtcgctgctg caccgcttcc gcgtcctgga ccgtggcaag aaaacgtccc gttgccaggt 10020 cctgatcgac gaggaaatcg tcgtgctgtt tgctggcgac cactacacga aattcatatg 10080 ggagaagtac cgcaagctgt cgccgacggc ccgacggatg ttcgactatt tcagctcgca 10140 ccgggagccg tacccgctca agctggaaac cttccgcctc atgtgcggat cggattccac 10200 ccgcgtgaag aagtggcgcg agcaggtcgg cgaagcctgc gaagagttgc gaggcagcgg 10260 cctggtggaa cacgcctggg tcaatgatga cctggtgcat tgcaaacgct agggccttgt 10320 ggggtcagtt ccggctgggg gttcagcagc cactcgatcg aggtcccaat acgcaaaccg 10380 cctctccccg cgcgttggcc gattcattaa tgcagctggc acgacaggtt tcccgactgg 10440 aaagcgggca gtgagcgcaa cgcaattaat gtgagttagc tcactcatta ggcaccccag 10500 gctttacact ttatgcttcc ggctcgtatg ttgtgtggaa ttgtgagcgg ataacaattt 10560 cacacaggaa acagctatga ccatgattac gccaagcttc catgggatat cgagatctcc 10620 tgcagagctc tagagtcgag actagtctcg acgggcccgg taccccctcg agggggccgc 10680 acttaagtta cgcgtggatc gtggagcttt cgggttttaa ctataacggt cctaaggtag 10740 cgaactcggg tcttgcctta atcccaacaa ccggattatc tacacggatt tcaatagctg 10800 atatagcgaa tcaccgagat taattaa 10827 <210> 46 <211> 506 <212> DNA <213> Artificial Sequence <220> <223> origin of replication <400> 46 atcacgtgct ataaaaataa ttataattta aattttttaa tataaatata taaattaaaa 60 atagaaagta aaaaaagaaa ttaaagaaaa aatagttttt gttttccgaa gatgtaaaag 120 actctagggg gatcgccaac aaatactacc ttttatcttg ctcttcctgc tctcaggtat 180 taatgccgaa ttgtttcatc ttgtctgtgt agaagaccac acacgaaaat cctgtgattt 240 tacattttac ttatcgttaa tcgaatgtat atctatttaa tctgcttttc ttgtctaata 300 aatatatatg taaagtacgc tttttgttga aattttttaa acctttgttt attttttttt 360 ttcttcattc cgtaactctt ctaccttctt tatttacttt ctaaaatcca aatacaaaac 420 ataaaaataa ataaacacag agtaaattcc caaattattc catcattaaa agatacgagg 480 cgcgtgtaag ttacaggcaa gcgatc 506 <210> 47 <211> 1020 <212> DNA <213> Artificial Sequence <220> <223> selectionmarker <400> 47 ttcaattcat catttttttt ttattctttt ttttgatttc ggtttccttg aaattttttt 60 gattcggtaa tctccgaaca gaaggaagaa cgaaggaagg agcacagact tagattggta 120 tatatacgca tatgtagtgt tgaagaaaca tgaaattgcc cagtattctt aacccaactg 180 cacagaacaa aaacctgcag gaaacgaaga taaatcatgt cgaaagctac atataaggaa 240 cgtgctgcta ctcatcctag tcctgttgct gccaagctat ttaatatcat gcacgaaaag 300 caaacaaact tgtgtgcttc attggatgtt cgtaccacca aggaattact ggagttagtt 360 gaagcattag gtcccaaaat ttgtttacta aaaacacatg tggatatctt gactgatttt 420 tccatggagg gcacagttaa gccgctaaag gcattatccg ccaagtacaa ttttttactc 480 ttcgaagaca gaaaatttgc tgacattggt aatacagtca aattgcagta ctctgcgggt 540 gtatacagaa tagcagaatg ggcagacatt acgaatgcac acggtgtggt gggcccaggt 600 attgttagcg gtttgaagca ggcggcagaa gaagtaacaa aggaacctag aggccttttg 660 atgttagcag aattgtcatg caagggctcc ctatctactg gagaatatac taagggtact 720 gttgacattg cgaagagcga caaagatttt gttatcggct ttattgctca aagagacatg 780 ggtggaagag atgaaggtta cgattggttg attatgacac ccggtgtggg tttagatgac 840 aagggagacg cattgggtca acagtataga accgtggatg atgtggtctc tacaggatct 900 gacattatta ttgttggaag aggactattt gcaaagggaa gggatgctaa ggtagagggt 960 gaacgttaca gaaaagcagg ctgggaagca tatttgagaa gatgcggcca gcaaaactaa 1020 <210> 48 <211> 228 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 E <400> 48 atgtactcat tcgtttcgga agagacaggt acgttaatag ttaatagcgt acttcttttt 60 cttgctttcg tggtattctt gctagttaca ctagccattc ttactgcgct tcgattgtgt 120 gcgtactgtt gcaatattgt taacgtgagt cttgtaaaac cttcttttta cgtttactct 180 cgtgttaaaa atctgaattc ttctcgggtt cctgatcttc tggtctaa 228 <210> 49 <211> 669 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 M <400> 49 atggcagatt ccaacggtac tattaccgtt gaggagctga aaaagctcct tgaacaatgg 60 aacctagtaa taggtttcct attccttaca tggatttgcc tgctgcaatt tgcctatgcc 120 aacaggaata ggtttttgta catcattaag ttgattttcc tctggctgtt atggccagta 180 actttagctt gttttgtgct tgctgctgtt tacagaataa attggatcac cggtggaatt 240 gctattgcaa tggcttgtct tgtaggattg atgtggctaa gctacttcat tgcttctttc 300 agactgtttg cgcgtacgcg ttccatgtgg tcattcaatc cagaaactaa cattcttctc 360 aacgtgccac tccatggaac tattctgact agaccgcttc tagaaagtga actcgtaatc 420 ggagctgtta tccttcgtgg acatcttcgt attgctggac atcatctagg acgctgtgac 480 atcaaggatc tacctaaaga aatcactgtt gctacatcac gaacgctttc ttattacaaa 540 ttgggagctt cacagcgtgt agcaggtgat tcaggttttg ctgcatatag tcgctacagg 600 attggcaact ataaattaaa cacagaccat tccagtagca gtgacaatat tgctttgctt 660 gtacagtaa 669 <210> 50 <211> 1260 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 N <400> 50 atgtctgata atggacctca aaatcagcga aatgcacctc gcattacgtt tggtggacca 60 tcagattcaa ctggcagtaa ccagaatgga gaacgaagtg gtgcgcgatc aaaacaacgc 120 cgcccgcaag gtttacccaa taatactgcg tcttggttca ccgctctcac tcaacatggc 180 aaggaagatt taaaattccc tcgaggacaa ggcgttccaa ttaacaccaa tagcagtcca 240 gatgaccaaa ttggctacta ccgccgcgcc acaagacgaa ttcgtggtgg tgatggtaaa 300 atgaaagatc tcagtccaag atggtatttc tactatctag gaactgggcc agaagctgga 360 cttccttatg gtgctaacaa agatggcatc atatgggttg caactgaggg agccttgaat 420 acaccaaaag atcacattgg caccagaaat cctgctaaca atgctgcaat cgtgctacaa 480 cttcctcaag gaacaacatt accaaaaggt ttttacgcag aagggtctag aggtggaagt 540 caagcctctt ctagatcatc atcacgtagt cgcaacagtt caagaaattc aactccaggt 600 tcaagtagag gaacttctcc tgctagaatg gctggaaatg gaggtgatgc tgctcttgct 660 ttgttactac ttgacagatt gaaccagctt gagagcaaaa tgtctggtaa aggccaacaa 720 caacaaggcc aaactgtcac taagaaatct gctgctgagg cttctaagaa gcctagacaa 780 aaacgtactg ccactaaagc atacaatgta acacaagctt tcggcagacg tggtccagaa 840 caaactcaag gaaattttgg ggatcaggaa ctaatcagac aaggaactga ttacaaacat 900 tggccgcaaa ttgcacaatt tgctccttct gcttcagcgt tctttggaat gtcgagaatt 960 ggaatggaag tcacaccttc gggaacatgg ttgacctata caggtgccat caaattggat 1020 gacaaagatc caaatttcaa agatcaagtc attttgctga ataagcatat tgacgcatac 1080 aaaacattcc caccaacaga gcctaaaaag gacaaaaaga agaaggctga tgaaactcaa 1140 gccttaccgc agagacagaa gaaacagcaa actgtgactc ttcttcctgc tgcagatttg 1200 gatgatttct ccaaacaatt gcaacaatcc atgagcagtg ctgactcaac tcaggcctaa 1260 <210> 51 <211> 21290 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 ORF1ab <400> 51 atggagagcc ttgtccctgg tttcaacgag aaaacacacg tccaactcag tttgcctgtt 60 ttacaggttc gcgacgtgtt agtacgtggt tttggagatt cagtggaaga agtcttatca 120 gaggcacgtc aacatcttaa agatggcact tgtggcttag tagaagttga aaaaggcgtt 180 ttgcctcaac ttgaacagcc ctatgtgttc atcaaacgtt ctgatgctag aactgcacct 240 catggtcatg ttatggttga gctggtagca gaattagaag gtattcagta cggtcgtagt 300 ggtgagacat taggtgtttt agttcctcat gtgggcgaaa taccagtggc ttaccgcaaa 360 gttcttctta gaaagaacgg taataaagga gctggtggcc atagttacgg cgctgattta 420 aagtcatttg acttaggcga cgagcttggc actgatcctt atgaagattt ccaagaaaac 480 tggaacacta aacatagcag tggtgttacc cgtgaactca tgcgtgagtt aaatggaggt 540 gcatacactc gctatgtcga taacaacttc tgtggacctg atggttaccc tcttgagtgc 600 attaaagacc ttctagcacg tgctggtaaa gcttcatgca ctttgtccga acaactggac 660 tttattgaca ctaagagggg tgtatactgc tgccgtgaac atgagcatga aattgcttgg 720 tacacggaac gttctgaaaa gagctatgaa ttgcagacac cttttgaaat taaactggca 780 aagaaatttg acaccttcaa tggggaatgt ccaaattttg tatttcccct caattccata 840 atcaagacta ttcaaccaag ggttgaaaag aaaaagcttg atggctttat gggtagaatt 900 cgatctgtct atccagttgc gtcaccaaat gaatgcaacc aaatgtgcct ttcaactctc 960 atgaagtgtg atcattgtgg tgaaacttca tggcagacgg gcgattttgt taaagccact 1020 tgcgaatttt gtggcactga gaatttgact aaagaaggtg ccactacttg tggttactta 1080 ccccaaaatg ctgttgttaa aatttactgt ccagcatgtc acaattcaga agtaggacct 1140 gagcatagtc ttgccgaata ccataatgaa tctggcttga aaaccattct tcgtaagggt 1200 ggtcgcacta ttgcttttgg aggatgtgtg ttctcttatg ttggttgcca taacaagtgt 1260 gcttattggg ttccacgtgc ttcagctaac ataggttgta accatacagg tgttgttgga 1320 gaaggttccg aaggtcttaa tgacaacctt cttgaaatac tccaaaaaga gaaagtcaac 1380 atcaatattg ttggtgactt taaacttaat gaagagatcg ccattatttt ggcatctttt 1440 tctgcttcca caagtgcttt tgtggaaact gtgaaaggtt tggattataa agcattcaaa 1500 cagattgttg aatcctgtgg taattttaag gttacaaagg gaaaagctaa aaaaggtgcc 1560 tggaatattg gtgaacagaa atcaatactg agtcctcttt atgcatttgc atcagaggct 1620 gctcgtgttg tacgatcaat tttctcccgc actcttgaaa ctgctcaaaa ttctgtgcgt 1680 gttttacaga aggccgctat aacaatacta gatggaattt cacagtattc actgagactc 1740 attgatgcta tgatgttcac atctgatttg gctactaaca atctagttgt aatggcctac 1800 attacaggtg gtgttgttca gttgacttcg cagtggctaa ctaacatctt tggcactgtt 1860 tatgaaaaac tcaaacccgt ccttgattgg cttgaagaga agtttaagga aggtgtagag 1920 tttcttagag acggttggga gattgttaaa ttcatctcaa cctgtgcttg tgaaattgtc 1980 ggtggacaaa ttgtcacctg tgctaaggaa attaaggaga gtgttcagac attctttaag 2040 cttgtaaaca agtttttggc tttgtgtgct gactctatca ttattggtgg agctaaactt 2100 aaagccttga atttaggtga aacatttgtc acgcactcaa agggattgta cagaaagtgt 2160 gttaaatcca gagaagaaac tggcctactc atgcctctaa aagccccaaa agaaattatc 2220 ttcttagagg gagaaacact tcccacagaa gtgttaacag aggaagttgt cttgaaaact 2280 ggtgatttac aaccattaga acaacctact agtgaagctg ttgaagctcc attggttggt 2340 acaccagttt gtattaacgg gcttatgttg ctcgaaatca aagacacaga aaagtactgt 2400 gcccttgcac ctaatatgat ggtaacaaac aataccttca cactcaaagg cggtgcacca 2460 acaaaggtta cttttggtga tgacactgtg atagaagtgc aaggttacaa gagtgtgaat 2520 atcacttttg aacttgatga aaggattgat aaagtactta atgagaagtg ctctgcctat 2580 acagttgaac tcggtacaga agtaaatgag ttcgcctgtg ttgtggcaga tgctgtcata 2640 aaaactttgc aaccagtatc tgaattactt acaccactgg gcattgattt agatgagtgg 2700 agtatggcta catactactt atttgatgag tctggtgagt ttaaattggc ttcacatatg 2760 tattgttctt tctaccctcc agatgaggat gaagaagaag gtgattgtga agaagaagag 2820 tttgagccat caactcaata tgagtatggt actgaagatg attaccaagg taaacctttg 2880 gaatttggtg ccacttctgc tgctttacaa cctgaagaag aacaagaaga agattggtta 2940 gatgatgata gtcaacaaac tgttggtcaa caagacggca gtgaggacaa tcagacaact 3000 actattcaaa caattgttga ggttcaacct caattagaga tggaacttac accagttgtt 3060 cagactattg aagtgaatag ttttagtggt tatcttaaac ttactgacaa tgtatacatc 3120 aagaatgcag acattgtgga agaagctaaa aaggtaaaac caacagtggt tgttaatgca 3180 gccaatgttt accttaaaca tggaggaggt gttgcaggag ccttaaataa ggctactaac 3240 aatgccatgc aagttgaatc tgatgattac atagctacta atggaccact taaagtgggt 3300 ggtagttgtg ttttaagcgg acacaatctt gctaaacact gtttacatgt tgtcggccca 3360 aatgttaaca aaggtgaaga tattcaactt cttaagagtg cttatgaaaa ttttaaccag 3420 cacgaagttc tacttgcacc attattatca gctggtattt ttggtgctga ccctatacat 3480 tctttaagag tttgtgtaga tactgttcgc acaaatgtct acttagctgt ctttgataaa 3540 aatctctatg acaaacttgt ttcaagcttt ttggaaatga agagtgaaaa gcaagttgaa 3600 caaaagatcg ctgagattcc taaagaggaa gttaagccat ttataactga aagtaaacct 3660 tcagttgaac agagaaaaca agatgataag aagatcaaag cttgtgttga agaagttaca 3720 acaactctgg aagaaactaa gttcctcaca gaaaacttgc tcctttatat cgacattaat 3780 ggcaatcttc atccagattc tgccactctt gttagtgaca ttgacatcac tttcttaaag 3840 aaagatgctc catatatagt gggtgatgtt gttcaagagg gtgttttaac tgctgtggtt 3900 atacctacta aaaaggctgg tggcactact gaaatgctag cgaaagcttt gagaaaagtg 3960 ccaacagaca attatataac cacttacccg ggtcagggtt taaatggtta cactgtagag 4020 gaggcaaaga cagtgcttaa aaagtgtaaa agtgcctttt acattctacc atctattatc 4080 tctaatgaga agcaagaaat tcttggaact gtttcttgga atttgcgaga aatgcttgca 4140 catgcagaag aaacacgcaa attaatgcct gtctgtgtgg aaactaaagc catagtttca 4200 actatacagc gtaaatataa gggtatcaag atacaagagg gtgtggttga ttatggtgct 4260 agattttact tttacaccag taaaacaact gtagcgtcac ttatcaacac acttaacgat 4320 ctaaatgaaa ctcttgttac aatgccactt ggctatgtaa cacatggctt aaatttggaa 4380 gaagctgctc ggtatatgag atctctcaaa gtgccagcta cagtttctgt ttcttcacct 4440 gatgctgtta cagcgtataa tggttatctt acttcttctt ctaaaacacc tgaagaacat 4500 tttattgaaa ccatctcact tgctggttcc tataaagatt ggtcctattc tggacaatct 4560 acacaactag gtatagaatt tcttaagaga ggtgataaaa gtgtatatta cacgtccaat 4620 cctaccacat tccacctaga tggtgaagtt atcacctttg acaatcttaa gacacttctt 4680 tctttgagag aagtgaggac tattaaggtg tttacaacag tagacaacat taacctccac 4740 acgcaagttg tggacatgtc aatgacatat ggacaacagt ttggtccaac ttatttggat 4800 ggagctgatg ttactaagat aaaacctcat aactcacatg aaggtaaaac attttacgtt 4860 ttgcctaatg atgacactct acgtgttgag gcttttgagt actaccacac aactgatcct 4920 agttttctgg gtaggtacat gtcagcatta aatcacacta aaaagtggaa atacccacaa 4980 gttaatggtt taacttcgat taaatgggca gataacaact gttatcttgc cactgcattg 5040 ttaacactcc aacaaataga gttgaagttt aatccacctg ctctacaaga tgcttattac 5100 agagcaaggg ctggtgaagc tgctaacttt tgtgcactta tcttagccta ctgtaataag 5160 acagtaggtg agttaggtga tgttagagaa acaatgagtt acttgtttca acatgccaat 5220 ttagattctt gcaaaagagt cttgaacgtg gtgtgtaaaa cttgtggaca acagcagaca 5280 acccttaagg gtgtagaagc tgttatgtac atgggcacac tttcttatga acaattcaag 5340 aaaggtgttc agataccttg tacgtgtggt aaacaagcta caaaatatct agtacaacag 5400 gagtcacctt ttgttatgat gtcagcacca cctgctcagt atgaacttaa gcatggtaca 5460 tttacttgtg ctagtgagta cactggtaat taccagtgtg gtcactataa gcatataact 5520 tctaaggaaa ctttgtattg catagacggt gctttactta caaagtcctc agaatacaaa 5580 ggtcctatta cggatgtttt ctacaaagaa aacagttaca caacaaccat aaaaccagtt 5640 acttataagt tggatggtgt tgtttgtaca gaaattgacc ctaagttgga caattattat 5700 aagaaggaca actcttattt cacagagcaa ccaattgatc ttgtaccaaa ccaaccatat 5760 ccaaacgcaa gcttcgataa ttttaagttc gtatgcgata atatcaaatt tgctgatgat 5820 ctcaaccagt taactggtta taagaaacct gcttcaagag agcttaaagt tacatttttc 5880 cctgacttaa atggtgatgt ggtggctatt gattataaac actacacacc ctcttttaag 5940 aaaggagcta aattgttaca taagcctatt gtttggcatg ttaacaatgc aactaataaa 6000 gccacgtata aaccaaatac ctggtgtata cgttgtcttt ggagcacaaa accagttgaa 6060 acatcaaatt cgtttgatgt actgaagtca gaggacgcgc agggaatgga taatcttgca 6120 tgtgaagatc taaaaccagt ctctgaagaa gtagtggaaa atcctaccat acagaaagac 6180 gttcttgagt gtaatgtgaa aactaccgaa gttgtaggag acattatact taaaccagca 6240 aataatagtt tgaagatcac agaagaggtt ggccacacag atctaatggc tgcttatgta 6300 gacaattcta gtcttactat taagaaacct aatgaactct ctagagtatt aggtttgaaa 6360 acccttgcta ctcatggttt agctgctgtt aatagtgtcc cttgggatac tatagctaat 6420 tatgctaagc cttttcttaa caaagttgtt agtacaacta ctaacatagt tacacggtgt 6480 cttaatcgtg tttgtactaa ttatatgcct tacttcttta ctttattgct acaattgtgt 6540 acttttacta gaagtacaaa ttctagaatc aaggcatcta tgccgactac tatagcaaag 6600 aatactgtta agagtgtcgg taaattttgt ctagaggctt catttaatta tctcaagtca 6660 cctaactttt ctaagctgat aaacattatc atctggtttt tgctattaag tgtttgccta 6720 ggttctttaa tctactcaac cgctgcttta ggtgttttaa tgtctaattt aggcatgcct 6780 tcttactgta ctggttacag agaaggctat ttgaactcta ctaatgtcac tattgcaacc 6840 tactgtactg gatctatacc ttgtagtgtt tgtcttagtg gtttagattc tttagacacc 6900 tatccttctc ttgaaactat acagattacc atttcatctt tcaaatggga tttaactgct 6960 tttggcttag ttgcagagtg gtttttggca tatattcttt tcactaggtt tttctatgta 7020 cttggattgg ctgcaatcat gcaattgttt ttcagctatt ttgcagtcca ttttattagt 7080 aactcttggc ttatgtggct tataattaat cttgtgcaga tggccccgat ttcagctatg 7140 gttagaatgt acatcttctt tgcctcattt tattatgtgt ggaaaagtta tgtgcatgtt 7200 gtagacggtt gtaattcatc aacttgtatg atgtgttaca aacgtaatag agcaacaaga 7260 gtcgaatgta caactattgt taatggtgtt agaaggtcct tttatgtcta tgctaatgga 7320 ggtaaaggct tttgcaaact acacaattgg aattgtgtta attgtgatac attctgtgct 7380 ggtagtacat ttattagtga tgaagttgcg agagacttgt cactacagtt taaaagacca 7440 ataaatccta ctgaccaatc ttcttacatc gttgatagtg ttacagtgaa gaatggttcc 7500 atccatcttt actttgataa agctggtcaa aagacttatg aaagacattc tctctctcat 7560 tttgttaact tagacaacct gagagctaat aacactaaag gttcattgcc tattaatgtt 7620 atcgttttcg acggtaaatc aaaatgtgaa gaatcatctg caaaatcagc gtctgtttac 7680 tacagtcagc ttatgtgtca acctatactg ttactagatc aggcattagt gtctgatgtt 7740 ggtgatagtg cggaagttgc agttaaaatg tttgatgctt acgttaatac gttttcatca 7800 acttttaacg taccaatgga aaaactcaaa acactagttg caactgcaga agctgaactt 7860 gcaaagaatg tgtccttaga caatgtctta tctacgttta tttcagcagc tcggcaaggg 7920 tttgttgatt cagatgtaga aactaaagat gttgttgaat gtcttaaatt gtcacatcaa 7980 tctgacatag aagttactgg cgatagttgt aataactata tgctcaccta taacaaagtt 8040 gaaaacatga caccccgtga ccttggtgct tgtattgact gtagtgctag acatattaat 8100 gcgcaggtag caaaaagtca caacattgct ttgatatgga acgttaaaga tttcatgtca 8160 ttgtctgaac aactacgaaa acaaatacgt agtgctgcta aaaagaataa cttacccttc 8220 aagttgacat gtgcaactac tagacaagtt gttaatgttg taacaacaaa gatagcactt 8280 aagggtggta aaattgtgaa taactggttg aagcagctta ttaaagttac acttgtgttc 8340 ctttttgttg ctgctatttt ctatctgata acacctgttc atgtcatgtc taaacatact 8400 gacttttcaa gtgaaatcat aggatacaag gctattgatg gtggtgtcac tcgtgacata 8460 gcatctacag atacttgttt tgctaacaaa catgctgatt ttgacacatg gtttagccag 8520 cgtggtggta gttatactaa tgacaaagct tgcccattga ttgctgcagt cataacaaga 8580 gaagtgggtt ttgtcgttcc tggtttgcct ggaacgatat tacgcacaac taatggtgac 8640 tttttgcatt tcttacctag agtttttagt gcagttggta acatctgtta cacaccatca 8700 aaacttatag agtacactga ctttgcaaca tcagcttgtg ttttggctgc tgaatgtaca 8760 atttttaaag acgcttctgg taagccagta ccatattgtt atgataccaa tgtactagaa 8820 ggttctgttg cttatgaaag tttacgccct gacacacgtt atgtgctcat ggatggctct 8880 attattcaat ttcctaacac ctaccttgaa ggttctgtaa gagtggtaac aacttttgat 8940 tctgagtact gtaggcacgg cacttgtgaa agatcagaag ctggtgtttg tgtatctact 9000 agtggtagat gggtacttaa caacgattat tacagatctt taccaggagt tttctgtggt 9060 gtagatgctg taaatttgct tactaacatg tttacaccac taattcaacc tattggtgct 9120 ttggacatat cagcatctat agtagctggt ggtattgtag ctatcgtagt aacatgcctt 9180 gcctactatt ttatgaggtt tagacgtgct tttggtgaat acagtcatgt agttgccttt 9240 aatactctcc tattccttat gtcattcact gtactctgtt taacaccagt ttactcattc 9300 ttacctggtg tttattctgt tatttacctg tacttgacat tttatctgac taatgatgtt 9360 tcttttctcg cacatattca gtggatggtt atgttcacac ctttagtacc tttctggata 9420 acaattgctt acatcatttg tatttccaca aagcatttct attggttctt tagtaattac 9480 ctaaagagac gtgtagtctt taatggtgtt tcctttagta cttttgaaga agctgcgctg 9540 tgcacctttt tgttaaataa ggagatgtat ctaaagttgc gtagtgatgt gctattacct 9600 cttacgcaat ataatagata cttagctctt tataacaagt acaagtattt cagtggagca 9660 atggatacaa ctagctacag agaagctgct tgttgtcatc tcgcaaaggc tctcaatgac 9720 ttcagtaact caggttctga tgttctttac caaccaccac aaacctctat cacctcagct 9780 gttttgcaga gtggttttag aaaaatggca ttcccatctg gtaaagttga gggttgtatg 9840 gtacaagtaa cttgtggtac aactacactt aacggtcttt ggcttgatga cgtagtttac 9900 tgtccaagac atgtgatctg cacctctgaa gatatgctta accctaatta tgaagatcta 9960 ctcatccgta agtctaatca taacttcttg gtacaggctg gtaatgttca actcagggtt 10020 attggacatt ctatgcaaaa ttgtgtactt aagcttaagg ttgatacagc caatcctaag 10080 acacctaagt ataagtttgt tcgcattcaa ccaggacaga ctttttcagt gttagcttgt 10140 tacaatggtt caccatctgg tgtttaccaa tgtgctatga ggcccaattt cactattaag 10200 ggttcattcc ttaatggttc atgtggtagt gttggtttta acatagatta tgactgtgtc 10260 tctttttgtt acatgcacca tatggaatta ccaactggag ttcatgctgg cacagactta 10320 gaaggtaact tttatggacc ttttgttgac aggcaaacag cacaagcagc tggtacagat 10380 acaactatta cagttaatgt tcttgcttgg ttgtacgctg ctgttataaa tggagacagg 10440 tggtttctca atcgatttac cacaactctt aatgacttta accttgtggc tatgaagtac 10500 aattatgaac ctctaacaca agaccatgtt gacatactag gacctctttc tgctcaaact 10560 ggaattgccg ttttagatat gtgtgcttca ttaaaagaac ttctgcaaaa tggtatgaat 10620 ggacgtacca tattgggtag tgctttatta gaagatgagt ttacaccttt tgatgttgtt 10680 agacaatgct caggtgttac tttccaaagt gcagtgaaaa gaacaatcaa gggtacacac 10740 cactggttgt tactcacaat tttgacttca cttttagttt tagtccagag tactcaatgg 10800 tctttgttct ttttcttcta cgaaaatgcc tttttacctt ttgctatggg tattattgct 10860 atgtctgctt ttgcaatgat gtttgtcaaa cataagcatg catttctctg tttgtttttg 10920 ttaccttctc ttgccactgt agcttacttt aatatggtct acatgcctgc tagttgggtg 10980 atgcgtatta tgacatggtt ggatatggtt gatactagtt tgtctggttt taagctaaaa 11040 gactgtgtta tgtatgcatc agctgtagtg ttactaatcc ttatgacagc aagaactgtg 11100 tatgatgatg gtgctaggag agtgtggaca cttatgaatg tcttgacact cgtttataaa 11160 gtttactatg gcaacgcttt agatcaagcc atttccatgt gggctcttat aatctctgtt 11220 acttctaact actcaggtgt agttacaact gtcatgtttt tggccagagg tattgttttt 11280 atgtgtgttg agtattgccc tattttcttc ataactggta atacacttca gtgtataatg 11340 ctagtctatt gtttcttagg ctatttttgt acttgttact tcggcctctt ttgtttactc 11400 aaccgctact ttagactgac tcttggtgtt tatgattact tagtgtctac acaggagttt 11460 agatatatga attcacaggg actactccca cccaagaata gcatagatgc cttcaaactc 11520 aacattaaat tgttgggtgt tggtggcaaa ccttgtatca aagtagccac tgtacagtct 11580 aaaatgtcag atgtaaagtg cacatcagta gtcttactct cagttttgca acaactcaga 11640 gtagaatcat catctaaatt gtgggctcaa tgtgtccagt tacacaatga cattctctta 11700 gctaaagata ctactgaagc ctttgaaaaa atggtttcac tactttctgt tttgctttcc 11760 atgcagggtg ctgtagacat aaacaagctt tgtgaagaaa tgctggacaa cagggcaacc 11820 ttacaagcta tagcctcaga gtttagttcc cttccatcat atgcagcttt tgctactgct 11880 caagaagctt atgagcaggc tgttgctaat ggtgattctg aagttgttct taaaaagttg 11940 aagaagtctt tgaatgtggc taaatctgaa tttgaccgtg atgcagccat gcaacgtaag 12000 ttggaaaaga tggctgatca agctatgacc caaatgtata aacaggctag atctgaggac 12060 aagagggcaa aagttactag tgctatgcag acaatgcttt tcactatgct tagaaagttg 12120 gataatgatg cactcaacaa cattatcaac aatgcaagag atggttgtgt tcccttgaac 12180 ataatacctc ttacaacagc agccaaacta atggttgtca taccagacta caacacatat 12240 aagaatacgt gtgatggtac aacatttact tatgcatcag cattgtggga aatccaacag 12300 gttgtagatg cagatagtaa aattgttcag cttagtgaaa ttagtatgga caattcacct 12360 aatttagcat ggcctcttat tgtaacagct ttaagggcca attctgctgt caaattacag 12420 aataatgagc ttagtcctgt tgcactaaga caaatgtctt gtgctgccgg tactacacaa 12480 actgcttgca ctgatgacaa tgcgttagct tactacaaca caacaaaggg aggtaggttt 12540 gtacttgcac tgttatccga tttacaggat ttgaaatggg ctagattccc taagagtgat 12600 ggaactggta ctatctatac agaactggaa ccaccttgta ggtttgttac agacacacct 12660 aaaggtccta aagtgaagta tctttacttc atcaaaggat taaacaacct aaatagaggt 12720 atggtacttg gtagtttagc tgccacagta cgtttacaag ctggtaatgc aacagaagtt 12780 cctgctaatt caactgtact ttctttctgt gcttttgctg tagatgctgc taaagcttac 12840 aaagattatc tagctagtgg gggacaacca atcactaatt gtgttaagat gttgtgtaca 12900 cacactggta ctggtcaggc aataacagtt acaccggaag ccaatatgga tcaagaatcc 12960 tttggtggtg catcgtgttg tctgtactgc cgttgtcata tagatcatcc aaatcctaaa 13020 ggattttgtg acttaaaagg taagtatgta caaataccta caacttgtgc taatgaccct 13080 gtgggtttta cacttaaaaa cacagtctgt accgtctgcg gtatgtggaa aggttatggt 13140 tgtagttgtg atcaactccg cgaacccatg cttcagtcag ctgatgcaca atcgttttta 13200 aacgggtttg cggtgtaagt gcagcccgtc ttacaccgtg cggcacaggc actagtactg 13260 atgtcgtata tagagctttt gacatctaca atgataaagt agctggtttt gctaagttcc 13320 taaaaactaa ttgttgtcgc ttccaagaaa aggacgaaga tgacaatctc attgattctt 13380 actttgtagt taagagacac actttctcta actaccaaca tgaagaaaca atttacaacc 13440 tgcttaagga ttgtccagct gttgctaaac atgacttctt taagtttaga atagacggtg 13500 acatggtacc acatatatca cgtcaacgtc ttactaaata cacaatggca gacctcgtct 13560 atgctttaag gcattttgat gaaggtaatt gtgacacatt aaaagaaata cttgtcacat 13620 acaattgttg tgatgatgac tacttcaata aaaaggactg gtatgatttt gtagaaaacc 13680 cagatatatt acgcgtatac gccaacttag gtgaacgtgt acgccaagct ttgttaaaaa 13740 cagtacagtt ctgtgatgcc atgcgaaatg ctggtattgt tggtgtactg acattagata 13800 atcaagatct caatggtaac tggtatgact ttggtgattt catacaaacc acgccaggta 13860 gtggagttcc tgttgtagac tcttattatt cattgctcat gcctatatta accttgacca 13920 gggctttaac tgcagagtca catgttgaca ctgacttaac aaagccttac attaagtggg 13980 atttgttaaa atacgacttc acggaagaga ggttaaaact ctttgaccgt tattttaaat 14040 actgggatca gacataccac ccaaattgtg ttaactgttt ggatgacaga tgcattctgc 14100 attgtgcaaa ctttaatgtt ctgttctcta cagtgttccc acctacaagt tttggaccac 14160 tagtgagaaa aatatttgtt gatggtgttc catttgtagt ttcaactgga taccacttca 14220 gagagctagg tgttgtacat aatcaggatg taaacttaca tagctctaga cttagtttta 14280 aggaattact tgtgtatgct gctgatcctg ctatgcatgc tgcttctggt aatctattac 14340 tagataaacg cactacgtgc ttttcagtag ctgcacttac taacaatgtt gcttttcaaa 14400 ctgtcaaacc cggtaatttt aacaaggact tctatgactt tgctgtgtct aagggtttct 14460 ttaaggaagg aagttctgtt gaattaaaac acttcttctt tgctcaggat ggtaatgctg 14520 ctatcagcga ttatgactac tatcgttata atctaccaac aatgtgtgat atcagacaac 14580 tactatttgt agttgaagtt gttgataagt actttgattg ttacgatggt ggctgtatta 14640 atgctaacca agtcatcgtc aacaacctag acaaatcagc tggttttcca tttaataaat 14700 ggggtaaggc tagactttat tatgattcca tgagttatga ggatcaagat gcacttttcg 14760 catatacaaa acgtaatgtc atccctacta taactcaaat gaaccttaag tatgccatta 14820 gtgcaaagaa tagagctcgc accgtagctg gtgtctctat ctgtagtact atgaccaata 14880 gacagtttca tcaaaaatta ctcaagtcaa tagccgccac tagaggagct actgtagtaa 14940 ttggaacaag caaattctat ggtggttggc acaacatgct caaaactgtt tatagtgatg 15000 tagaaaaccc tcaccttatg ggttgggatt atcctaaatg tgatagagcc atgcctaaca 15060 tgcttagaat tatggcctca cttgttcttg ctcgcaaaca tacaacgtgt tgtagcttgt 15120 cacaccgttt ctatagatta gctaatgagt gtgctcaagt attgagtgaa atggtcatgt 15180 gtggcggttc actatatgtt aaaccaggtg gaacctcatc aggagatgcc acaactgctt 15240 atgctaatag tgtgtttaac atttgtcaag ctgtcacggc caatgttaat gcacttttat 15300 ctactgatgg taacaaaatt gccgataagt atgtccgcaa tttacaacac agactttatg 15360 agtgtctcta tagaaataga gatgttgaca cagactttgt gaatgagttt tacgcatatt 15420 tgcgtaaaca tttctcaatg atgatactct ctgacgatgc tgttgtgtgt ttcaatagca 15480 cttatgcatc tcaaggtcta gtggctagca taaagaactt taagtcagtt ctttactatc 15540 aaaacaacgt ttttatgtct gaagcaaaat gttggactga gactgacctt actaaaggac 15600 ctcatgaatt ttgctctcaa catacaatgc tagttaaaca gggtgatgat tatgtgtacc 15660 ttccttaccc agatccatca agaatcctag gtgccggttg ttttgtagat gatatcgtaa 15720 aaacagatgg tacacttatg attgaacggt tcgtgtcttt agctatagat gcttacccac 15780 ttactaaaca tcctaatcag gagtatgctg atgtctttca tttgtactta caatacatac 15840 gtaagctaca tgatgagtta acaggacaca tgttagacat gtattctgtt atgcttacta 15900 atgataacac ttcaaggtat tgggaacctg agttttatga ggctatgtac acaccgcata 15960 cagtcttaca agctgttggt gcttgtgttc tttgcaattc acagacttca ttaagatgtg 16020 gtgcttgcat acgtagacca ttcttatgtt gtaaatgctg ttacgaccat gtcatctcaa 16080 catcacataa attagtcttg tctgttaatc cgtatgtttg caatgctcca ggttgtgatg 16140 tcacagatgt gactcaactt tacttaggag gtatgagcta ttactgtaag tcacataaac 16200 cacccattag ttttccattg tgtgctaatg gacaagtttt tggtctctac aagaatacat 16260 gtgttggtag cgataatgtt actgacttta atgcaattgc aacatgtgac tggacaaatg 16320 ctggtgatta cattttagct aacacctgta ctgaaagact caagcttttt gcagcagaaa 16380 cgctcaaagc tactgaggag acatttaaac tgtcttatgg tattgctact gtacgtgaag 16440 tgctgtctga cagagaatta catctttcat gggaagttgg taaacctaga ccaccactta 16500 accgaaatta tgtctttact ggttatcgtg taactaaaaa cagtaaagtg caaatcggag 16560 agtacacctt tgaaaaaggt gactatggtg atgctgttgt ttaccgaggt acaacaactt 16620 acaaactcaa cgttggtgat tattttgtgc tgacatcaca tacagtaatg ccattaagtg 16680 cacctacact agtgccacaa gagcactatg ttagaattac tggcttatac ccaacactca 16740 atatctcaga tgagttttct agcaatgttg caaattatca aaaggttggt atgcaaaagt 16800 attctacact ccagggacca cctggtactg gtaaaagtca ttttgctatt ggtctagctc 16860 tctactaccc ttctgctcgc atagtatata cagcttgctc tcatgcagct gttgatgcac 16920 tatgtgagaa ggcattaaaa tatttgccca tagacaaatg tagtagaatt atacctgcac 16980 gtgctcgtgt agagtgtttt gataaattca aggtgaattc aacattagaa cagtatgtct 17040 tttgtactgt aaatgcattg cctgagacga cagcagatat agttgtcttt gatgaaattt 17100 caatggccac aaattatgat ttgagtgttg tcaatgccag attacgtgct aagcactatg 17160 tgtacattgg tgatcctgct caattacctg caccacgcac attactaact aagggtacac 17220 tagaaccaga atatttcaat tcagtgtgta gacttatgaa aactataggt ccagacatgt 17280 tcctcggaac ttgtcgtaga tgtcctgctg aaattgttga cactgtgagt gctttggttt 17340 atgataataa gcttaaggca cataaagaca aatcagctca atgctttaaa atgttctaca 17400 agggtgttat cacgcatgat gtttcatctg caattaacag gccacaaata ggcgtggtaa 17460 gagaattcct tacacgtaac cctgcttgga gaaaagctgt ctttatttca ccttacaatt 17520 cccagaatgc tgtagcctca aagattttgg gactaccaac tcaaactgtt gattcatcac 17580 agggctcaga atatgactat gtcatattca ctcaaaccac tgaaacagct cactcttgta 17640 atgtaaacag attcaacgtt gctattacca gagcaaaagt aggcatactt tgcataatgt 17700 ctgatagaga cctttatgac aagttgcaat ttacaagtct tgaaattcca cgtaggaatg 17760 tggcaacttt acaagctgaa aatgtaacag gactctttaa agattgtagt aaggtaatca 17820 ctgggttaca tcctacacag gcacctacac acttaagtgt tgatactaaa ttcaaaactg 17880 aaggtttatg tgttgacata cctggcatac ctaaggacat gacctataga agattaatct 17940 ctatgatggg tttcaaaatg aattaccagg ttaatggtta ccctaacatg tttatcaccc 18000 gcgaagaagc tataagacat gtacgtgcat ggattggctt cgatgtcgaa ggttgtcatg 18060 ctactagaga agctgttggt accaatttac ctttacagct aggtttttct acaggtgtta 18120 acctagttgc tgtacctaca ggttatgttg atacacctaa taatacagat ttttccagag 18180 ttagtgctaa accaccgcct ggagatcaat ttaaacacct cataccactt atgtacaaag 18240 gacttccttg gaatgtagtg cgtataaaga ttgtccaaat gttaagtgac acacttaaaa 18300 atctctctga cagagtcgta tttgtcttat gggcacatgg ctttgagttg acatctatga 18360 agtattttgt gaagatcgga cctgagcgca catgttgtct atgtgataga cgtgctacat 18420 gcttttccac tgcttcagac acttatgcct gttggcatca ttctattgga tttgattacg 18480 tctataatcc gtttatgatt gatgttcaac aatggggttt tacaggtaac ctacaaagca 18540 accatgatct gtattgtcaa gtccatggta atgcacatgt agctagttgt gatgcaatca 18600 tgactaggtg tctagctgtc cacgagtgct ttgttaagcg tgttgactgg actattgaat 18660 atcctataat cggtgatgaa ctgaagatta atgcggcttg tagaaaggtt caacacatgg 18720 ttgttaaagc tgcattatta gcagacaaat tcccagttct tcacgacatt ggtaacccta 18780 aagctattaa gtgtgtacct caagctgatg tagaatggaa gttctatgat gcacagcctt 18840 gtagtgacaa agcttacaaa atagaagaac tgttctattc ttatgccaca cattctgaca 18900 aattcacaga tggtgtatgc ctattttgga attgcaatgt cgatagatat cctgctaatt 18960 ccattgtttg tagatttgac actagagtgc tatctaacct taacttgcct ggttgtgatg 19020 gtggcagttt gtatgtaaat aagcatgcat tccacacacc agcttttgat aaaagtgctt 19080 ttgttaatct aaagcaactt ccatttttct attactctga cagtccatgt gagtctcatg 19140 gaaaacaagt agtgtcagat atagattatg taccactaaa gtctgctacg tgtataacac 19200 gttgcaattt aggtggtgct gtctgtagac atcatgctaa tgagtacaga ttgtatctcg 19260 atgcttataa catgatgatc tcagctggct ttagcttgtg ggtttacaaa caatttgata 19320 cctataacct ctggaacact tttacaagac ttcagagttt agaaaatgtg gcttttaatg 19380 ttgtaaataa gggacacttt gatggacaac agggtgaagt accagtttct atcattaaca 19440 acactgttta cacaaaagtt gatggtgttg atgtagaatt gtttgagaac aaaaccacat 19500 tacctgttaa tgtagcattt gagctttggg ctaagcgcaa cattaaacca gtaccagagg 19560 tgaaaatact caataatttg ggtgtggaca ttgctgctaa tactgtgatc tgggactaca 19620 aaagagatgc tccagcacat atatctacta ttggtgtttg ttctatgact gacatagcca 19680 agaaaccaac tgaaacgatt tgtgcaccac tcactgtctt ttttgatggt agagttgatg 19740 gtcaagtaga cttatttaga aatgcccgta atggtgttct tattacagaa ggtagtgtta 19800 aaggtttaca accatctgta ggtcccaaac aagctagtct taatggagtc acattaattg 19860 gagaagccgt aaaaacacag ttcaattatt acaagaaagt ggatggtgtt gtccaacaat 19920 tacctgaaac ttactttact cagagtagaa acttacagga atttaagccc aggagtcaaa 19980 tggaaattga tttcttagaa cttgctatgg atgaattcat tgaacggtat aaattagaag 20040 gctatgcctt cgaacatatc gtttatggag attttagtca tagtcagtta ggtggtttac 20100 atctactgat tggactagct aaacgtttta aggaatcacc ttttgaactt gaagatttta 20160 ttcctatgga cagtacagtt aaaaactact tcataacaga tgcgcaaaca ggttcatcta 20220 agtgtgtgtg ttctgttatt gatcttttac ttgatgactt cgttgaaata ataaagtccc 20280 aagatttatc tgtagtttct aaggttgtca aagtgactat tgactataca gaaatctcat 20340 ttatgctttg gtgtaaagat ggccatgtag aaacatttta cccaaaatta caatctagtc 20400 aagcgtggca accgggtgtt gctatgccta atctttacaa aatgcaaaga atgctattag 20460 aaaagtgtga ccttcaaaat tatggtgata gtgcaacatt acctaaaggc ataatgatga 20520 atgtcgcaaa atatactcaa ctgtgtcaat atttaaacac actgacatta gctgtaccct 20580 ataatatgag agttatccat tttggtgctg gttctgataa aggagttgca ccaggtacag 20640 ctgttttaag acaatggttg cctacaggta cgctgcttgt cgattcagat cttaatgact 20700 ttgtctctga tgcagattca actttgattg gtgattgtgc aactgtacat acagctaata 20760 aatgggatct cattattagt gatatgtacg accctaagac taagaatgtc acaaaagaaa 20820 acgactctaa agagggtttt ttcacttaca tttgtgggtt tatacaacaa aagctagctc 20880 ttggaggttc cgtggctata aagataacag aacattcttg gaatgctgat ctttataagc 20940 tcatgggaca cttcgcatgg tggacagcct ttgttactaa tgtgaatgcg tcatcatctg 21000 aagcattttt aatcggatgt aactaccttg gcaaaccacg cgaacaaata gatggttatg 21060 tcatgcatgc aaattacata ttttggagga atacaaatcc aattcagctt tcttcttatt 21120 ctttattcga catgagtaaa ttccccctta aattaagggg tactgctgtt atgtctttaa 21180 aagaaggtca aatcaatgat atgattctct ctcttcttag taaaggtaga cttataatta 21240 gagaaaacaa cagagttgtt atttctagtg atgttcttgt taacaactaa 21290 <210> 52 <211> 828 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 ORF3a <400> 52 atggatttgt ttatgagaat cttcacaatt ggaactgtaa ctttgaagca aggtgaaatc 60 aaggatgcta ctccttcaga ttttgttaga gctactgcaa cgataccgat acaagcatca 120 cttcctttcg gatggcttat tgttggcgtt gcacttcttg ctgtttttca gagcgcttcc 180 aaaatcataa ccctcaaaaa gagatggcaa ctagcactct ccaagggtgt tcactttgtt 240 tgcaacttgc tgttgttgtt tgtaacagtt tactcacatc ttttgcttgt tgctgctggc 300 cttgaagccc cttttctcta tctttatgct ttagtctact tcttgcagag tataaacttt 360 gtacgcataa taatgaggct ttggctttgc tggaaatgcc gttccaaaaa cccattactt 420 tatgatgcca actattttct ttgctggcat actaattgtt acgactattg tataccttac 480 aatagtgtaa cttcttcaat tgtcattact tcaggtgatg gcacaacaag tcctatttct 540 gaacatgact accagattgg tggttatact gaaaaatggg aatctggagt aaaagactgt 600 gttgtattac acagttactt cacttcagac tattaccagc tgtactcaac tcaattgagt 660 acagacactg gtgttgaaca tgttaccttc ttcatctaca ataaaatcgt tgatgagcct 720 gaagaacatg tccaaattca cacaatcgac gtttcatccg gagttgttaa tccagtaatg 780 gaaccaattt atgatgaacc gacgacgact actagcgtgc ctttgtaa 828 <210> 53 <211> 186 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 ORF6 <400> 53 atgtttcatc tcgttgactt tcaggttact atagcagaga tattactaat catcatgagg 60 acttttaaag tttccatttg gaatcttgat tacatcataa acctcataat taagaactta 120 agcaagtcac taactgagaa taaatattct caactagacg aggagcagcc aatggagatt 180 gattaa 186 <210> 54 <211> 366 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 ORF7a <400> 54 atgaaaatta ttcttttctt ggcactgata acactcgcta cttgtgagct ttatcactac 60 caagagtgtg ttagaggtac aacagtactt ttaaaagaac cttgctcgtc gggaacatac 120 gagggcaatt caccatttca tcctctagct gataacaaat ttgcactgac ttgctttagc 180 actcaatttg cttttgcttg tcctgacggc gtaaaacacg tctatcagtt acgtgccaga 240 tcagtttcac ctaaactgtt catcagacaa gaggaagttc aagaacttta ctctccaatt 300 tttcttattg ttgcggcaat agtgtttata acactttgct tcacactcaa aagaaagaca 360 gaatga 366 <210> 55 <211> 366 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 ORF8 <400> 55 atgaaatttc ttgttttctt aggaatcatc acaactgtag ctgcatttca ccaagaatgt 60 agtttacagt catgtactca acatcaacca tatgtagttg atgacccgtg tcctattcac 120 ttctattcta aatggtatat cagagtagga gctagaaaat cagcaccttt aattgaattg 180 tgcgtggatg aggctggttc taaatcaccc attcagtaca tcgatatcgg taattataca 240 gtttcctgtt taccttttac aattaactgc caggaaccta aattgggtag tcttgtagtg 300 cgttgttcgt tctacgagga ctttttagag tatcatgacg ttcgtgttgt tttagatttc 360 atctaa 366 <210> 56 <211> 265 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 5'UTR <400> 56 attaaaggtt tataccttcc caggtaacaa accaaccaac tttcgatctc ttgtagatct 60 gttctctaaa cgaactttaa aatctgtgtg gctgtcactc ggctgcatgc ttagtgcact 120 cacgcagtat aattaataac taattactgt cgttgacagg acacgagtaa ctcgtctatc 180 ttctgcaggc tgcttacggt ttcgtccgtg ttgcagccga tcatcagcac atctaggttt 240 cgtccgggtg tgaccgaaag gtaag 265 <210> 57 <211> 206 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 3'UTR <400> 57 caatctttaa tcagtgtgta acattaggga ggacttgaaa gagccaccac attttcaccg 60 aggccacgcg gagtacgatc gagtgtacag tgaacaatgc tagggagagc tgcctatatg 120 gaagagccct aatgtgtaaa attaatttta gtagtgctat ccccatgtga ttttaatagc 180 ttcttaggag aatgacaaaa aaaaac 206 <210> 58 <211> 13203 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 orf1a <400> 58 atggagagcc ttgtccctgg tttcaacgag aaaacacacg tccaactcag tttgcctgtt 60 ttacaggttc gcgacgtgtt agtacgtggt tttggagatt cagtggaaga agtcttatca 120 gaggcacgtc aacatcttaa agatggcact tgtggcttag tagaagttga aaaaggcgtt 180 ttgcctcaac ttgaacagcc ctatgtgttc atcaaacgtt ctgatgctag aactgcacct 240 catggtcatg ttatggttga gctggtagca gaattagaag gtattcagta cggtcgtagt 300 ggtgagacat taggtgtttt agttcctcat gtgggcgaaa taccagtggc ttaccgcaaa 360 gttcttctta gaaagaacgg taataaagga gctggtggcc atagttacgg cgctgattta 420 aagtcatttg acttaggcga cgagcttggc actgatcctt atgaagattt ccaagaaaac 480 tggaacacta aacatagcag tggtgttacc cgtgaactca tgcgtgagtt aaatggaggt 540 gcatacactc gctatgtcga taacaacttc tgtggacctg atggttaccc tcttgagtgc 600 attaaagacc ttctagcacg tgctggtaaa gcttcatgca ctttgtccga acaactggac 660 tttattgaca ctaagagggg tgtatactgc tgccgtgaac atgagcatga aattgcttgg 720 tacacggaac gttctgaaaa gagctatgaa ttgcagacac cttttgaaat taaactggca 780 aagaaatttg acaccttcaa tggggaatgt ccaaattttg tatttcccct caattccata 840 atcaagacta ttcaaccaag ggttgaaaag aaaaagcttg atggctttat gggtagaatt 900 cgatctgtct atccagttgc gtcaccaaat gaatgcaacc aaatgtgcct ttcaactctc 960 atgaagtgtg atcattgtgg tgaaacttca tggcagacgg gcgattttgt taaagccact 1020 tgcgaatttt gtggcactga gaatttgact aaagaaggtg ccactacttg tggttactta 1080 ccccaaaatg ctgttgttaa aatttactgt ccagcatgtc acaattcaga agtaggacct 1140 gagcatagtc ttgccgaata ccataatgaa tctggcttga aaaccattct tcgtaagggt 1200 ggtcgcacta ttgcttttgg aggatgtgtg ttctcttatg ttggttgcca taacaagtgt 1260 gcttattggg ttccacgtgc ttcagctaac ataggttgta accatacagg tgttgttgga 1320 gaaggttccg aaggtcttaa tgacaacctt cttgaaatac tccaaaaaga gaaagtcaac 1380 atcaatattg ttggtgactt taaacttaat gaagagatcg ccattatttt ggcatctttt 1440 tctgcttcca caagtgcttt tgtggaaact gtgaaaggtt tggattataa agcattcaaa 1500 cagattgttg aatcctgtgg taattttaag gttacaaagg gaaaagctaa aaaaggtgcc 1560 tggaatattg gtgaacagaa atcaatactg agtcctcttt atgcatttgc atcagaggct 1620 gctcgtgttg tacgatcaat tttctcccgc actcttgaaa ctgctcaaaa ttctgtgcgt 1680 gttttacaga aggccgctat aacaatacta gatggaattt cacagtattc actgagactc 1740 attgatgcta tgatgttcac atctgatttg gctactaaca atctagttgt aatggcctac 1800 attacaggtg gtgttgttca gttgacttcg cagtggctaa ctaacatctt tggcactgtt 1860 tatgaaaaac tcaaacccgt ccttgattgg cttgaagaga agtttaagga aggtgtagag 1920 tttcttagag acggttggga gattgttaaa ttcatctcaa cctgtgcttg tgaaattgtc 1980 ggtggacaaa ttgtcacctg tgctaaggaa attaaggaga gtgttcagac attctttaag 2040 cttgtaaaca agtttttggc tttgtgtgct gactctatca ttattggtgg agctaaactt 2100 aaagccttga atttaggtga aacatttgtc acgcactcaa agggattgta cagaaagtgt 2160 gttaaatcca gagaagaaac tggcctactc atgcctctaa aagccccaaa agaaattatc 2220 ttcttagagg gagaaacact tcccacagaa gtgttaacag aggaagttgt cttgaaaact 2280 ggtgatttac aaccattaga acaacctact agtgaagctg ttgaagctcc attggttggt 2340 acaccagttt gtattaacgg gcttatgttg ctcgaaatca aagacacaga aaagtactgt 2400 gcccttgcac ctaatatgat ggtaacaaac aataccttca cactcaaagg cggtgcacca 2460 acaaaggtta cttttggtga tgacactgtg atagaagtgc aaggttacaa gagtgtgaat 2520 atcacttttg aacttgatga aaggattgat aaagtactta atgagaagtg ctctgcctat 2580 acagttgaac tcggtacaga agtaaatgag ttcgcctgtg ttgtggcaga tgctgtcata 2640 aaaactttgc aaccagtatc tgaattactt acaccactgg gcattgattt agatgagtgg 2700 agtatggcta catactactt atttgatgag tctggtgagt ttaaattggc ttcacatatg 2760 tattgttctt tctaccctcc agatgaggat gaagaagaag gtgattgtga agaagaagag 2820 tttgagccat caactcaata tgagtatggt actgaagatg attaccaagg taaacctttg 2880 gaatttggtg ccacttctgc tgctttacaa cctgaagaag aacaagaaga agattggtta 2940 gatgatgata gtcaacaaac tgttggtcaa caagacggca gtgaggacaa tcagacaact 3000 actattcaaa caattgttga ggttcaacct caattagaga tggaacttac accagttgtt 3060 cagactattg aagtgaatag ttttagtggt tatcttaaac ttactgacaa tgtatacatc 3120 aagaatgcag acattgtgga agaagctaaa aaggtaaaac caacagtggt tgttaatgca 3180 gccaatgttt accttaaaca tggaggaggt gttgcaggag ccttaaataa ggctactaac 3240 aatgccatgc aagttgaatc tgatgattac atagctacta atggaccact taaagtgggt 3300 ggtagttgtg ttttaagcgg acacaatctt gctaaacact gtttacatgt tgtcggccca 3360 aatgttaaca aaggtgaaga tattcaactt cttaagagtg cttatgaaaa ttttaaccag 3420 cacgaagttc tacttgcacc attattatca gctggtattt ttggtgctga ccctatacat 3480 tctttaagag tttgtgtaga tactgttcgc acaaatgtct acttagctgt ctttgataaa 3540 aatctctatg acaaacttgt ttcaagcttt ttggaaatga agagtgaaaa gcaagttgaa 3600 caaaagatcg ctgagattcc taaagaggaa gttaagccat ttataactga aagtaaacct 3660 tcagttgaac agagaaaaca agatgataag aagatcaaag cttgtgttga agaagttaca 3720 acaactctgg aagaaactaa gttcctcaca gaaaacttgc tcctttatat cgacattaat 3780 ggcaatcttc atccagattc tgccactctt gttagtgaca ttgacatcac tttcttaaag 3840 aaagatgctc catatatagt gggtgatgtt gttcaagagg gtgttttaac tgctgtggtt 3900 atacctacta aaaaggctgg tggcactact gaaatgctag cgaaagcttt gagaaaagtg 3960 ccaacagaca attatataac cacttacccg ggtcagggtt taaatggtta cactgtagag 4020 gaggcaaaga cagtgcttaa aaagtgtaaa agtgcctttt acattctacc atctattatc 4080 tctaatgaga agcaagaaat tcttggaact gtttcttgga atttgcgaga aatgcttgca 4140 catgcagaag aaacacgcaa attaatgcct gtctgtgtgg aaactaaagc catagtttca 4200 actatacagc gtaaatataa gggtatcaag atacaagagg gtgtggttga ttatggtgct 4260 agattttact tttacaccag taaaacaact gtagcgtcac ttatcaacac acttaacgat 4320 ctaaatgaaa ctcttgttac aatgccactt ggctatgtaa cacatggctt aaatttggaa 4380 gaagctgctc ggtatatgag atctctcaaa gtgccagcta cagtttctgt ttcttcacct 4440 gatgctgtta cagcgtataa tggttatctt acttcttctt ctaaaacacc tgaagaacat 4500 tttattgaaa ccatctcact tgctggttcc tataaagatt ggtcctattc tggacaatct 4560 acacaactag gtatagaatt tcttaagaga ggtgataaaa gtgtatatta cacgtccaat 4620 cctaccacat tccacctaga tggtgaagtt atcacctttg acaatcttaa gacacttctt 4680 tctttgagag aagtgaggac tattaaggtg tttacaacag tagacaacat taacctccac 4740 acgcaagttg tggacatgtc aatgacatat ggacaacagt ttggtccaac ttatttggat 4800 ggagctgatg ttactaagat aaaacctcat aactcacatg aaggtaaaac attttacgtt 4860 ttgcctaatg atgacactct acgtgttgag gcttttgagt actaccacac aactgatcct 4920 agttttctgg gtaggtacat gtcagcatta aatcacacta aaaagtggaa atacccacaa 4980 gttaatggtt taacttcgat taaatgggca gataacaact gttatcttgc cactgcattg 5040 ttaacactcc aacaaataga gttgaagttt aatccacctg ctctacaaga tgcttattac 5100 agagcaaggg ctggtgaagc tgctaacttt tgtgcactta tcttagccta ctgtaataag 5160 acagtaggtg agttaggtga tgttagagaa acaatgagtt acttgtttca acatgccaat 5220 ttagattctt gcaaaagagt cttgaacgtg gtgtgtaaaa cttgtggaca acagcagaca 5280 acccttaagg gtgtagaagc tgttatgtac atgggcacac tttcttatga acaattcaag 5340 aaaggtgttc agataccttg tacgtgtggt aaacaagcta caaaatatct agtacaacag 5400 gagtcacctt ttgttatgat gtcagcacca cctgctcagt atgaacttaa gcatggtaca 5460 tttacttgtg ctagtgagta cactggtaat taccagtgtg gtcactataa gcatataact 5520 tctaaggaaa ctttgtattg catagacggt gctttactta caaagtcctc agaatacaaa 5580 ggtcctatta cggatgtttt ctacaaagaa aacagttaca caacaaccat aaaaccagtt 5640 acttataagt tggatggtgt tgtttgtaca gaaattgacc ctaagttgga caattattat 5700 aagaaggaca actcttattt cacagagcaa ccaattgatc ttgtaccaaa ccaaccatat 5760 ccaaacgcaa gcttcgataa ttttaagttc gtatgcgata atatcaaatt tgctgatgat 5820 ctcaaccagt taactggtta taagaaacct gcttcaagag agcttaaagt tacatttttc 5880 cctgacttaa atggtgatgt ggtggctatt gattataaac actacacacc ctcttttaag 5940 aaaggagcta aattgttaca taagcctatt gtttggcatg ttaacaatgc aactaataaa 6000 gccacgtata aaccaaatac ctggtgtata cgttgtcttt ggagcacaaa accagttgaa 6060 acatcaaatt cgtttgatgt actgaagtca gaggacgcgc agggaatgga taatcttgca 6120 tgtgaagatc taaaaccagt ctctgaagaa gtagtggaaa atcctaccat acagaaagac 6180 gttcttgagt gtaatgtgaa aactaccgaa gttgtaggag acattatact taaaccagca 6240 aataatagtt tgaagatcac agaagaggtt ggccacacag atctaatggc tgcttatgta 6300 gacaattcta gtcttactat taagaaacct aatgaactct ctagagtatt aggtttgaaa 6360 acccttgcta ctcatggttt agctgctgtt aatagtgtcc cttgggatac tatagctaat 6420 tatgctaagc cttttcttaa caaagttgtt agtacaacta ctaacatagt tacacggtgt 6480 cttaatcgtg tttgtactaa ttatatgcct tacttcttta ctttattgct acaattgtgt 6540 acttttacta gaagtacaaa ttctagaatc aaggcatcta tgccgactac tatagcaaag 6600 aatactgtta agagtgtcgg taaattttgt ctagaggctt catttaatta tctcaagtca 6660 cctaactttt ctaagctgat aaacattatc atctggtttt tgctattaag tgtttgccta 6720 ggttctttaa tctactcaac cgctgcttta ggtgttttaa tgtctaattt aggcatgcct 6780 tcttactgta ctggttacag agaaggctat ttgaactcta ctaatgtcac tattgcaacc 6840 tactgtactg gatctatacc ttgtagtgtt tgtcttagtg gtttagattc tttagacacc 6900 tatccttctc ttgaaactat acagattacc atttcatctt tcaaatggga tttaactgct 6960 tttggcttag ttgcagagtg gtttttggca tatattcttt tcactaggtt tttctatgta 7020 cttggattgg ctgcaatcat gcaattgttt ttcagctatt ttgcagtcca ttttattagt 7080 aactcttggc ttatgtggct tataattaat cttgtgcaga tggccccgat ttcagctatg 7140 gttagaatgt acatcttctt tgcctcattt tattatgtgt ggaaaagtta tgtgcatgtt 7200 gtagacggtt gtaattcatc aacttgtatg atgtgttaca aacgtaatag agcaacaaga 7260 gtcgaatgta caactattgt taatggtgtt agaaggtcct tttatgtcta tgctaatgga 7320 ggtaaaggct tttgcaaact acacaattgg aattgtgtta attgtgatac attctgtgct 7380 ggtagtacat ttattagtga tgaagttgcg agagacttgt cactacagtt taaaagacca 7440 ataaatccta ctgaccaatc ttcttacatc gttgatagtg ttacagtgaa gaatggttcc 7500 atccatcttt actttgataa agctggtcaa aagacttatg aaagacattc tctctctcat 7560 tttgttaact tagacaacct gagagctaat aacactaaag gttcattgcc tattaatgtt 7620 atcgttttcg acggtaaatc aaaatgtgaa gaatcatctg caaaatcagc gtctgtttac 7680 tacagtcagc ttatgtgtca acctatactg ttactagatc aggcattagt gtctgatgtt 7740 ggtgatagtg cggaagttgc agttaaaatg tttgatgctt acgttaatac gttttcatca 7800 acttttaacg taccaatgga aaaactcaaa acactagttg caactgcaga agctgaactt 7860 gcaaagaatg tgtccttaga caatgtctta tctacgttta tttcagcagc tcggcaaggg 7920 tttgttgatt cagatgtaga aactaaagat gttgttgaat gtcttaaatt gtcacatcaa 7980 tctgacatag aagttactgg cgatagttgt aataactata tgctcaccta taacaaagtt 8040 gaaaacatga caccccgtga ccttggtgct tgtattgact gtagtgctag acatattaat 8100 gcgcaggtag caaaaagtca caacattgct ttgatatgga acgttaaaga tttcatgtca 8160 ttgtctgaac aactacgaaa acaaatacgt agtgctgcta aaaagaataa cttacccttc 8220 aagttgacat gtgcaactac tagacaagtt gttaatgttg taacaacaaa gatagcactt 8280 aagggtggta aaattgtgaa taactggttg aagcagctta ttaaagttac acttgtgttc 8340 ctttttgttg ctgctatttt ctatctgata acacctgttc atgtcatgtc taaacatact 8400 gacttttcaa gtgaaatcat aggatacaag gctattgatg gtggtgtcac tcgtgacata 8460 gcatctacag atacttgttt tgctaacaaa catgctgatt ttgacacatg gtttagccag 8520 cgtggtggta gttatactaa tgacaaagct tgcccattga ttgctgcagt cataacaaga 8580 gaagtgggtt ttgtcgttcc tggtttgcct ggaacgatat tacgcacaac taatggtgac 8640 tttttgcatt tcttacctag agtttttagt gcagttggta acatctgtta cacaccatca 8700 aaacttatag agtacactga ctttgcaaca tcagcttgtg ttttggctgc tgaatgtaca 8760 atttttaaag acgcttctgg taagccagta ccatattgtt atgataccaa tgtactagaa 8820 ggttctgttg cttatgaaag tttacgccct gacacacgtt atgtgctcat ggatggctct 8880 attattcaat ttcctaacac ctaccttgaa ggttctgtaa gagtggtaac aacttttgat 8940 tctgagtact gtaggcacgg cacttgtgaa agatcagaag ctggtgtttg tgtatctact 9000 agtggtagat gggtacttaa caacgattat tacagatctt taccaggagt tttctgtggt 9060 gtagatgctg taaatttgct tactaacatg tttacaccac taattcaacc tattggtgct 9120 ttggacatat cagcatctat agtagctggt ggtattgtag ctatcgtagt aacatgcctt 9180 gcctactatt ttatgaggtt tagacgtgct tttggtgaat acagtcatgt agttgccttt 9240 aatactctcc tattccttat gtcattcact gtactctgtt taacaccagt ttactcattc 9300 ttacctggtg tttattctgt tatttacctg tacttgacat tttatctgac taatgatgtt 9360 tcttttctcg cacatattca gtggatggtt atgttcacac ctttagtacc tttctggata 9420 acaattgctt acatcatttg tatttccaca aagcatttct attggttctt tagtaattac 9480 ctaaagagac gtgtagtctt taatggtgtt tcctttagta cttttgaaga agctgcgctg 9540 tgcacctttt tgttaaataa ggagatgtat ctaaagttgc gtagtgatgt gctattacct 9600 cttacgcaat ataatagata cttagctctt tataacaagt acaagtattt cagtggagca 9660 atggatacaa ctagctacag agaagctgct tgttgtcatc tcgcaaaggc tctcaatgac 9720 ttcagtaact caggttctga tgttctttac caaccaccac aaacctctat cacctcagct 9780 gttttgcaga gtggttttag aaaaatggca ttcccatctg gtaaagttga gggttgtatg 9840 gtacaagtaa cttgtggtac aactacactt aacggtcttt ggcttgatga cgtagtttac 9900 tgtccaagac atgtgatctg cacctctgaa gatatgctta accctaatta tgaagatcta 9960 ctcatccgta agtctaatca taacttcttg gtacaggctg gtaatgttca actcagggtt 10020 attggacatt ctatgcaaaa ttgtgtactt aagcttaagg ttgatacagc caatcctaag 10080 acacctaagt ataagtttgt tcgcattcaa ccaggacaga ctttttcagt gttagcttgt 10140 tacaatggtt caccatctgg tgtttaccaa tgtgctatga ggcccaattt cactattaag 10200 ggttcattcc ttaatggttc atgtggtagt gttggtttta acatagatta tgactgtgtc 10260 tctttttgtt acatgcacca tatggaatta ccaactggag ttcatgctgg cacagactta 10320 gaaggtaact tttatggacc ttttgttgac aggcaaacag cacaagcagc tggtacagat 10380 acaactatta cagttaatgt tcttgcttgg ttgtacgctg ctgttataaa tggagacagg 10440 tggtttctca atcgatttac cacaactctt aatgacttta accttgtggc tatgaagtac 10500 aattatgaac ctctaacaca agaccatgtt gacatactag gacctctttc tgctcaaact 10560 ggaattgccg ttttagatat gtgtgcttca ttaaaagaac ttctgcaaaa tggtatgaat 10620 ggacgtacca tattgggtag tgctttatta gaagatgagt ttacaccttt tgatgttgtt 10680 agacaatgct caggtgttac tttccaaagt gcagtgaaaa gaacaatcaa gggtacacac 10740 cactggttgt tactcacaat tttgacttca cttttagttt tagtccagag tactcaatgg 10800 tctttgttct ttttcttcta cgaaaatgcc tttttacctt ttgctatggg tattattgct 10860 atgtctgctt ttgcaatgat gtttgtcaaa cataagcatg catttctctg tttgtttttg 10920 ttaccttctc ttgccactgt agcttacttt aatatggtct acatgcctgc tagttgggtg 10980 atgcgtatta tgacatggtt ggatatggtt gatactagtt tgtctggttt taagctaaaa 11040 gactgtgtta tgtatgcatc agctgtagtg ttactaatcc ttatgacagc aagaactgtg 11100 tatgatgatg gtgctaggag agtgtggaca cttatgaatg tcttgacact cgtttataaa 11160 gtttactatg gcaacgcttt agatcaagcc atttccatgt gggctcttat aatctctgtt 11220 acttctaact actcaggtgt agttacaact gtcatgtttt tggccagagg tattgttttt 11280 atgtgtgttg agtattgccc tattttcttc ataactggta atacacttca gtgtataatg 11340 ctagtctatt gtttcttagg ctatttttgt acttgttact tcggcctctt ttgtttactc 11400 aaccgctact ttagactgac tcttggtgtt tatgattact tagtgtctac acaggagttt 11460 agatatatga attcacaggg actactccca cccaagaata gcatagatgc cttcaaactc 11520 aacattaaat tgttgggtgt tggtggcaaa ccttgtatca aagtagccac tgtacagtct 11580 aaaatgtcag atgtaaagtg cacatcagta gtcttactct cagttttgca acaactcaga 11640 gtagaatcat catctaaatt gtgggctcaa tgtgtccagt tacacaatga cattctctta 11700 gctaaagata ctactgaagc ctttgaaaaa atggtttcac tactttctgt tttgctttcc 11760 atgcagggtg ctgtagacat aaacaagctt tgtgaagaaa tgctggacaa cagggcaacc 11820 ttacaagcta tagcctcaga gtttagttcc cttccatcat atgcagcttt tgctactgct 11880 caagaagctt atgagcaggc tgttgctaat ggtgattctg aagttgttct taaaaagttg 11940 aagaagtctt tgaatgtggc taaatctgaa tttgaccgtg atgcagccat gcaacgtaag 12000 ttggaaaaga tggctgatca agctatgacc caaatgtata aacaggctag atctgaggac 12060 aagagggcaa aagttactag tgctatgcag acaatgcttt tcactatgct tagaaagttg 12120 gataatgatg cactcaacaa cattatcaac aatgcaagag atggttgtgt tcccttgaac 12180 ataatacctc ttacaacagc agccaaacta atggttgtca taccagacta caacacatat 12240 aagaatacgt gtgatggtac aacatttact tatgcatcag cattgtggga aatccaacag 12300 gttgtagatg cagatagtaa aattgttcag cttagtgaaa ttagtatgga caattcacct 12360 aatttagcat ggcctcttat tgtaacagct ttaagggcca attctgctgt caaattacag 12420 aataatgagc ttagtcctgt tgcactaaga caaatgtctt gtgctgccgg tactacacaa 12480 actgcttgca ctgatgacaa tgcgttagct tactacaaca caacaaaggg aggtaggttt 12540 gtacttgcac tgttatccga tttacaggat ttgaaatggg ctagattccc taagagtgat 12600 ggaactggta ctatctatac agaactggaa ccaccttgta ggtttgttac agacacacct 12660 aaaggtccta aagtgaagta tctttacttc atcaaaggat taaacaacct aaatagaggt 12720 atggtacttg gtagtttagc tgccacagta cgtttacaag ctggtaatgc aacagaagtt 12780 cctgctaatt caactgtact ttctttctgt gcttttgctg tagatgctgc taaagcttac 12840 aaagattatc tagctagtgg gggacaacca atcactaatt gtgttaagat gttgtgtaca 12900 cacactggta ctggtcaggc aataacagtt acaccggaag ccaatatgga tcaagaatcc 12960 tttggtggtg catcgtgttg tctgtactgc cgttgtcata tagatcatcc aaatcctaaa 13020 ggattttgtg acttaaaagg taagtatgta caaataccta caacttgtgc taatgaccct 13080 gtgggtttta cacttaaaaa cacagtctgt accgtctgcg gtatgtggaa aggttatggt 13140 tgtagttgtg atcaactccg cgaacccatg cttcagtcag ctgatgcaca atcgttttta 13200 aac 13203 <210> 59 <211> 8088 <212> DNA <213> Artificial Sequence <220> <223> SARS-CoV-2 orf1b <400> 59 cgggtttgcg gtgtaagtgc agcccgtctt acaccgtgcg gcacaggcac tagtactgat 60 gtcgtatata gagcttttga catctacaat gataaagtag ctggttttgc taagttccta 120 aaaactaatt gttgtcgctt ccaagaaaag gacgaagatg acaatctcat tgattcttac 180 tttgtagtta agagacacac tttctctaac taccaacatg aagaaacaat ttacaacctg 240 cttaaggatt gtccagctgt tgctaaacat gacttcttta agtttagaat agacggtgac 300 atggtaccac atatatcacg tcaacgtctt actaaataca caatggcaga cctcgtctat 360 gctttaaggc attttgatga aggtaattgt gacacattaa aagaaatact tgtcacatac 420 aattgttgtg atgatgacta cttcaataaa aaggactggt atgattttgt agaaaaccca 480 gatatattac gcgtatacgc caacttaggt gaacgtgtac gccaagcttt gttaaaaaca 540 gtacagttct gtgatgccat gcgaaatgct ggtattgttg gtgtactgac attagataat 600 caagatctca atggtaactg gtatgacttt ggtgatttca tacaaaccac gccaggtagt 660 ggagttcctg ttgtagactc ttattattca ttgctcatgc ctatattaac cttgaccagg 720 gctttaactg cagagtcaca tgttgacact gacttaacaa agccttacat taagtgggat 780 ttgttaaaat acgacttcac ggaagagagg ttaaaactct ttgaccgtta ttttaaatac 840 tgggatcaga cataccaccc aaattgtgtt aactgtttgg atgacagatg cattctgcat 900 tgtgcaaact ttaatgttct gttctctaca gtgttcccac ctacaagttt tggaccacta 960 gtgagaaaaa tatttgttga tggtgttcca tttgtagttt caactggata ccacttcaga 1020 gagctaggtg ttgtacataa tcaggatgta aacttacata gctctagact tagttttaag 1080 gaattacttg tgtatgctgc tgatcctgct atgcatgctg cttctggtaa tctattacta 1140 gataaacgca ctacgtgctt ttcagtagct gcacttacta acaatgttgc ttttcaaact 1200 gtcaaacccg gtaattttaa caaggacttc tatgactttg ctgtgtctaa gggtttcttt 1260 aaggaaggaa gttctgttga attaaaacac ttcttctttg ctcaggatgg taatgctgct 1320 atcagcgatt atgactacta tcgttataat ctaccaacaa tgtgtgatat cagacaacta 1380 ctatttgtag ttgaagttgt tgataagtac tttgattgtt acgatggtgg ctgtattaat 1440 gctaaccaag tcatcgtcaa caacctagac aaatcagctg gttttccatt taataaatgg 1500 ggtaaggcta gactttatta tgattccatg agttatgagg atcaagatgc acttttcgca 1560 tatacaaaac gtaatgtcat ccctactata actcaaatga accttaagta tgccattagt 1620 gcaaagaata gagctcgcac cgtagctggt gtctctatct gtagtactat gaccaataga 1680 cagtttcatc aaaaattact caagtcaata gccgccacta gaggagctac tgtagtaatt 1740 ggaacaagca aattctatgg tggttggcac aacatgctca aaactgttta tagtgatgta 1800 gaaaaccctc accttatggg ttgggattat cctaaatgtg atagagccat gcctaacatg 1860 cttagaatta tggcctcact tgttcttgct cgcaaacata caacgtgttg tagcttgtca 1920 caccgtttct atagattagc taatgagtgt gctcaagtat tgagtgaaat ggtcatgtgt 1980 ggcggttcac tatatgttaa accaggtgga acctcatcag gagatgccac aactgcttat 2040 gctaatagtg tgtttaacat ttgtcaagct gtcacggcca atgttaatgc acttttatct 2100 actgatggta acaaaattgc cgataagtat gtccgcaatt tacaacacag actttatgag 2160 tgtctctata gaaatagaga tgttgacaca gactttgtga atgagtttta cgcatatttg 2220 cgtaaacatt tctcaatgat gatactctct gacgatgctg ttgtgtgttt caatagcact 2280 tatgcatctc aaggtctagt ggctagcata aagaacttta agtcagttct ttactatcaa 2340 aacaacgttt ttatgtctga agcaaaatgt tggactgaga ctgaccttac taaaggacct 2400 catgaatttt gctctcaaca tacaatgcta gttaaacagg gtgatgatta tgtgtacctt 2460 ccttacccag atccatcaag aatcctaggt gccggttgtt ttgtagatga tatcgtaaaa 2520 acagatggta cacttatgat tgaacggttc gtgtctttag ctatagatgc ttacccactt 2580 actaaacatc ctaatcagga gtatgctgat gtctttcatt tgtacttaca atacatacgt 2640 aagctacatg atgagttaac aggacacatg ttagacatgt attctgttat gcttactaat 2700 gataacactt caaggtattg ggaacctgag ttttatgagg ctatgtacac accgcataca 2760 gtcttacaag ctgttggtgc ttgtgttctt tgcaattcac agacttcatt aagatgtggt 2820 gcttgcatac gtagaccatt cttatgttgt aaatgctgtt acgaccatgt catctcaaca 2880 tcacataaat tagtcttgtc tgttaatccg tatgtttgca atgctccagg ttgtgatgtc 2940 acagatgtga ctcaacttta cttaggaggt atgagctatt actgtaagtc acataaacca 3000 cccattagtt ttccattgtg tgctaatgga caagtttttg gtctctacaa gaatacatgt 3060 gttggtagcg ataatgttac tgactttaat gcaattgcaa catgtgactg gacaaatgct 3120 ggtgattaca ttttagctaa cacctgtact gaaagactca agctttttgc agcagaaacg 3180 ctcaaagcta ctgaggagac atttaaactg tcttatggta ttgctactgt acgtgaagtg 3240 ctgtctgaca gagaattaca tctttcatgg gaagttggta aacctagacc accacttaac 3300 cgaaattatg tctttactgg ttatcgtgta actaaaaaca gtaaagtgca aatcggagag 3360 tacacctttg aaaaaggtga ctatggtgat gctgttgttt accgaggtac aacaacttac 3420 aaactcaacg ttggtgatta ttttgtgctg acatcacata cagtaatgcc attaagtgca 3480 cctacactag tgccacaaga gcactatgtt agaattactg gcttataccc aacactcaat 3540 atctcagatg agttttctag caatgttgca aattatcaaa aggttggtat gcaaaagtat 3600 tctacactcc agggaccacc tggtactggt aaaagtcatt ttgctattgg tctagctctc 3660 tactaccctt ctgctcgcat agtatataca gcttgctctc atgcagctgt tgatgcacta 3720 tgtgagaagg cattaaaata tttgcccata gacaaatgta gtagaattat acctgcacgt 3780 gctcgtgtag agtgttttga taaattcaag gtgaattcaa cattagaaca gtatgtcttt 3840 tgtactgtaa atgcattgcc tgagacgaca gcagatatag ttgtctttga tgaaatttca 3900 atggccacaa attatgattt gagtgttgtc aatgccagat tacgtgctaa gcactatgtg 3960 tacattggtg atcctgctca attacctgca ccacgcacat tactaactaa gggtacacta 4020 gaaccagaat atttcaattc agtgtgtaga cttatgaaaa ctataggtcc agacatgttc 4080 ctcggaactt gtcgtagatg tcctgctgaa attgttgaca ctgtgagtgc tttggtttat 4140 gataataagc ttaaggcaca taaagacaaa tcagctcaat gctttaaaat gttctacaag 4200 ggtgttatca cgcatgatgt ttcatctgca attaacaggc cacaaatagg cgtggtaaga 4260 gaattcctta cacgtaaccc tgcttggaga aaagctgtct ttatttcacc ttacaattcc 4320 cagaatgctg tagcctcaaa gattttggga ctaccaactc aaactgttga ttcatcacag 4380 ggctcagaat atgactatgt catattcact caaaccactg aaacagctca ctcttgtaat 4440 gtaaacagat tcaacgttgc tattaccaga gcaaaagtag gcatactttg cataatgtct 4500 gatagagacc tttatgacaa gttgcaattt acaagtcttg aaattccacg taggaatgtg 4560 gcaactttac aagctgaaaa tgtaacagga ctctttaaag attgtagtaa ggtaatcact 4620 gggttacatc ctacacaggc acctacacac ttaagtgttg atactaaatt caaaactgaa 4680 ggtttatgtg ttgacatacc tggcatacct aaggacatga cctatagaag attaatctct 4740 atgatgggtt tcaaaatgaa ttaccaggtt aatggttacc ctaacatgtt tatcacccgc 4800 gaagaagcta taagacatgt acgtgcatgg attggcttcg atgtcgaagg ttgtcatgct 4860 actagagaag ctgttggtac caatttacct ttacagctag gtttttctac aggtgttaac 4920 ctagttgctg tacctacagg ttatgttgat acacctaata atacagattt ttccagagtt 4980 agtgctaaac caccgcctgg agatcaattt aaacacctca taccacttat gtacaaagga 5040 cttccttgga atgtagtgcg tataaagatt gtccaaatgt taagtgacac acttaaaaat 5100 ctctctgaca gagtcgtatt tgtcttatgg gcacatggct ttgagttgac atctatgaag 5160 tattttgtga agatcggacc tgagcgcaca tgttgtctat gtgatagacg tgctacatgc 5220 ttttccactg cttcagacac ttatgcctgt tggcatcatt ctattggatt tgattacgtc 5280 tataatccgt ttatgattga tgttcaacaa tggggtttta caggtaacct acaaagcaac 5340 catgatctgt attgtcaagt ccatggtaat gcacatgtag ctagttgtga tgcaatcatg 5400 actaggtgtc tagctgtcca cgagtgcttt gttaagcgtg ttgactggac tattgaatat 5460 cctataatcg gtgatgaact gaagattaat gcggcttgta gaaaggttca acacatggtt 5520 gttaaagctg cattattagc agacaaattc ccagttcttc acgacattgg taaccctaaa 5580 gctattaagt gtgtacctca agctgatgta gaatggaagt tctatgatgc acagccttgt 5640 agtgacaaag cttacaaaat agaagaactg ttctattctt atgccacaca ttctgacaaa 5700 ttcacagatg gtgtatgcct attttggaat tgcaatgtcg atagatatcc tgctaattcc 5760 attgtttgta gatttgacac tagagtgcta tctaacctta acttgcctgg ttgtgatggt 5820 ggcagtttgt atgtaaataa gcatgcattc cacacaccag cttttgataa aagtgctttt 5880 gttaatctaa agcaacttcc atttttctat tactctgaca gtccatgtga gtctcatgga 5940 aaacaagtag tgtcagatat agattatgta ccactaaagt ctgctacgtg tataacacgt 6000 tgcaatttag gtggtgctgt ctgtagacat catgctaatg agtacagatt gtatctcgat 6060 gcttataaca tgatgatctc agctggcttt agcttgtggg tttacaaaca atttgatacc 6120 tataacctct ggaacacttt tacaagactt cagagtttag aaaatgtggc ttttaatgtt 6180 gtaaataagg gacactttga tggacaacag ggtgaagtac cagtttctat cattaacaac 6240 actgtttaca caaaagttga tggtgttgat gtagaattgt ttgagaacaa aaccacatta 6300 cctgttaatg tagcatttga gctttgggct aagcgcaaca ttaaaccagt accagaggtg 6360 aaaatactca ataatttggg tgtggacatt gctgctaata ctgtgatctg ggactacaaa 6420 agagatgctc cagcacatat atctactatt ggtgtttgtt ctatgactga catagccaag 6480 aaaccaactg aaacgatttg tgcaccactc actgtctttt ttgatggtag agttgatggt 6540 caagtagact tatttagaaa tgcccgtaat ggtgttctta ttacagaagg tagtgttaaa 6600 ggtttacaac catctgtagg tcccaaacaa gctagtctta atggagtcac attaattgga 6660 gaagccgtaa aaacacagtt caattattac aagaaagtgg atggtgttgt ccaacaatta 6720 cctgaaactt actttactca gagtagaaac ttacaggaat ttaagcccag gagtcaaatg 6780 gaaattgatt tcttagaact tgctatggat gaattcattg aacggtataa attagaaggc 6840 tatgccttcg aacatatcgt ttatggagat tttagtcata gtcagttagg tggtttacat 6900 ctactgattg gactagctaa acgttttaag gaatcacctt ttgaacttga agattttatt 6960 cctatggaca gtacagttaa aaactacttc ataacagatg cgcaaacagg ttcatctaag 7020 tgtgtgtgtt ctgttattga tcttttactt gatgacttcg ttgaaataat aaagtcccaa 7080 gatttatctg tagtttctaa ggttgtcaaa gtgactattg actatacaga aatctcattt 7140 atgctttggt gtaaagatgg ccatgtagaa acattttacc caaaattaca atctagtcaa 7200 gcgtggcaac cgggtgttgc tatgcctaat ctttacaaaa tgcaaagaat gctattagaa 7260 aagtgtgacc ttcaaaatta tggtgatagt gcaacattac ctaaaggcat aatgatgaat 7320 gtcgcaaaat atactcaact gtgtcaatat ttaaacacac tgacattagc tgtaccctat 7380 aatatgagag ttatccattt tggtgctggt tctgataaag gagttgcacc aggtacagct 7440 gttttaagac aatggttgcc tacaggtacg ctgcttgtcg attcagatct taatgacttt 7500 gtctctgatg cagattcaac tttgattggt gattgtgcaa ctgtacatac agctaataaa 7560 tgggatctca ttattagtga tatgtacgac cctaagacta agaatgtcac aaaagaaaac 7620 gactctaaag agggtttttt cacttacatt tgtgggttta tacaacaaaa gctagctctt 7680 ggaggttccg tggctataaa gataacagaa cattcttgga atgctgatct ttataagctc 7740 atgggacact tcgcatggtg gacagccttt gttactaatg tgaatgcgtc atcatctgaa 7800 gcatttttaa tcggatgtaa ctaccttggc aaaccacgcg aacaaataga tggttatgtc 7860 atgcatgcaa attacatatt ttggaggaat acaaatccaa ttcagctttc ttcttattct 7920 ttattcgaca tgagtaaatt cccccttaaa ttaaggggta ctgctgttat gtctttaaaa 7980 gaaggtcaaa tcaatgatat gattctctct cttcttagta aaggtagact tataattaga 8040 gaaaacaaca gagttgttat ttctagtgat gttcttgtta acaactaa 8088

Claims (21)

  1. 적어도 4,000개의 염기를 갖는 완전 합성 장쇄 핵산으로서,
    임의의 배열로 4개의 서열 부분 A-D 중 적어도 2개를 포함하거나, 또는
    서열 부분 A-D에 따른 데옥시리보핵산 서열에 상응하는 리보핵산 서열을 포함하는 것을 특징으로 하는 핵산:
    여기서,
    i) 서열 부분 A는
    a) 서열 번호 50에 정의된 서열 또는 서열 번호 50에 정의된 서열과 적어도 98.5% 서열 동일성을 갖는 서열; 또는
    b) 서열 번호 3에 정의된 서열
    을 포함하고;
    ii) 서열 부분 B는
    a) 서열 번호 48에 정의된 서열 또는 서열 번호 48에 정의된 서열과 적어도 98.3% 서열 동일성을 갖는 서열; 또는
    b) 서열 번호 7에 정의된 서열
    을 포함하고;
    iii) 서열 부분 C는
    a) 서열 번호 49에 정의된 서열 또는 서열 번호 49에 정의된 서열과 적어도 97.2% 서열 동일성을 갖는 서열; 또는
    b) 서열 번호 11에 정의된 서열
    을 포함하고;
    iv) 서열 부분 D는 서열 번호 17에 정의된 서열 또는 서열 번호 17에 정의된 서열과 적어도 98.5% 서열 동일성을 갖는 서열을 포함한다.
  2. 제1항에 있어서, 정의된 서열에서 적어도 8,000개의 염기, 바람직하게는 적어도 20,000개의 염기를 갖는 것을 특징으로 하는 핵산.
  3. 제1항 또는 제2항에 있어서, 하기를 추가로 포함하는 핵산:
    a) 1.) 서열 번호 51에 의해 정의된 ORF1ab 서열 또는 서열 번호 51과 적어도 98.5% 서열 동일성을 갖는 서열; 또는
    2.) i) 서열 번호 59에 의해 정의된 ORF1b 서열 또는 서열 번호 59와 적어도 98.5% 서열 동일성을 갖는 서열; 및
    ii) 서열 번호 58에 의해 정의된 ORF1 서열 또는 서열 번호 58과 적어도 98.6% 서열 동일성을 갖는 서열;
    b) 서열 번호 52에 의해 정의된 ORF3a 서열 또는 서열 번호 52와 적어도 99% 서열 동일성을 갖는 서열; 및
    c) 서열 번호 54에 의해 정의된 ORF7a 서열 또는 서열 번호 54와 적어도 99.5% 서열 동일성을 갖는 서열.
  4. 제3항에 있어서, 하기를 추가로 포함하는 핵산:
    a) 서열 번호 53에 의해 정의된 ORF6 서열 또는 서열 번호 53과 적어도 94.1% 서열 동일성을 갖는 서열; 및/또는
    b) 서열 번호 55에 의해 정의된 ORF8 서열 또는 서열 번호 55와 적어도 99% 서열 동일성을 갖는 서열.
  5. 제1항 내지 제4항 중 어느 한 항에 있어서, 서열 부분 A 내지 C가 서열 번호 19에 따른 서열 또는 상응하는 리보핵산 서열에 상응하는 것을 특징으로 하는 핵산.
  6. 제1항 내지 제5항 중 어느 한 항에 있어서, 핵산이 임의의 배열로 4개의 서열 부분 A-D 중 적어도 3개 또는 서열 부분 A-D에 따른 데옥시리보핵산 서열에 상응하는 리보핵산 서열을 갖는 4개 서열 부분 중 적어도 3개를 포함하는 것을 특징으로 하는 핵산.
  7. 제1항 내지 제6항 중 어느 한 항에 있어서, 핵산이 임의의 배열로 4개의 서열 부분 A-D 또는 서열 부분 A-D에 따른 데옥시리보핵산 서열에 상응하는 리보핵산 서열을 갖는 4개의 서열 부분을 포함하는 것을 특징으로 하는 핵산.
  8. 제1항 내지 제7항 중 어느 한 항에 있어서,
    서열 번호 15
    서열 번호 28
    서열 번호 29 및
    서열 번호 30
    으로 이루어진 적어도 하나의 서열을 추가로 포함하거나,
    서열 부분인 서열 번호 15, 서열 번호 28, 서열 번호 29 및 서열 번호 30에 따른 데옥시리보핵산 서열 중 하나 또는 상응하는 리보핵산 서열을 포함하는 것을 특징으로 하는 핵산.
  9. 제1항 내지 제8항 중 어느 한 항에 있어서, 1,000,000개 염기의 최대 크기, 바람직하게는 200,000개 염기의 최대 크기를 갖는 것을 특징으로 하는 핵산.
  10. 제1항 내지 제9항 중 어느 한 항에 따른 핵산을 포함하는 벡터.
  11. 제10항에 있어서, 서열 번호 46 및 서열 번호 47에 의해 정의된 서열을 포함하는 벡터.
  12. 제10항 또는 제11항에 있어서, 플라스미드 벡터인 벡터.
  13. 제1항 내지 제9항 중 어느 한 항에 따른 2개 이상의 핵산을 포함하는 키트.
  14. 제13항에 있어서, 핵산이 적어도 하나의 플라스미드, 바람직하게는 2개 이상의 플라스미드에 존재하는 것인 키트.
  15. 제10항 내지 제12항 중 어느 한 항에 따른 적어도 하나의 벡터를 포함하는 생명공학적 생산 유닛.
  16. 제1항 내지 제9항 중 어느 한 항에 따른 적어도 하나의 핵산, 제10항 내지 제12항 중 어느 한 항에 따른 벡터, 제13항 또는 제14항에 따른 키트, 또는 제15항에 따른 생명공학적 생산 유닛을 사용하여 유전자 발현에 의해 수득 가능한 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질로서, 제1항 내지 제9항 중 어느 한 항에 따른 적어도 하나의 핵산을 패키징하는 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질.
  17. 제1항 내지 제9항 중 어느 한 항에 따른 적어도 하나의 핵산 및 생산 유기체에서 제1항 내지 제9항 중 어느 한 항에 따른 적어도 하나의 핵산, 제10항 내지 제12항 중 어느 한 항에 따른 벡터, 제13항 또는 제14항에 따른 키트를 사용하여 유전자 발현에 의해 수득 가능한 생성물을 포함하고, 특히 제16항에 따른 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신.
  18. 제17항에 있어서, 단백질 성분 a, b1, b2, c1, c2, d1 또는 d2로 이루어진 군으로부터 선택되는 적어도 2개의 분자적으로 정확하게 정의된 단백질 성분을 포함하고, 여기서,
    (i) 단백질 성분은
    a) SARS-CoV-2의 S 단백질과 유사한 서열 번호 14에 따른 서열 또는 서열 번호 14와 적어도 90% 서열 동일성을 갖는 서열; 또는
    b) SARS-CoV-2의 S 단백질과 유사한 서열 번호 18에 따른 서열 또는 서열 번호 18과 적어도 90% 서열 동일성을 갖는 서열
    을 포함하고;
    (ii) 단백질 성분 b1은
    a) SARS-CoV-2의 외피 단백질 E와 유사한 서열 번호 6에 따른 서열 또는 서열 번호 6과 적어도 90% 서열 동일성을 갖는 서열; 또는
    b) SARS-CoV-2의 외피 단백질 E와 유사한 서열 번호 21에 따른 서열 또는 서열 번호 21과 적어도 90% 서열 동일성을 갖는 서열
    을 포함하고;
    단백질 성분 b2는 MHV59A의 외피 단백질 E 또는 등가 단백질과 유사한 서열 번호 8에 따른 서열 또는 서열 번호 8과 적어도 90% 서열 동일성을 갖는 서열을 포함하고;
    (iii) 단백질 성분 c1은
    a) SARS-CoV-2의 외피 단백질 M과 유사한 서열 번호 10에 따른 서열 또는 서열 번호 10과 적어도 90% 서열 동일성을 갖는 서열; 또는
    b) SARS-CoV-2의 막 단백질 M과 유사한 서열 번호 22에 따른 서열 또는 서열 번호 22와 적어도 90% 서열 동일성을 갖는 서열
    을 포함하고;
    단백질 성분 c2는 MHV59A의 막 단백질 M 또는 등가 단백질과 유사한 서열 번호 12에 따른 서열 또는 서열 번호 12와 적어도 90% 서열 동일성을 갖는 서열을 포함하고;
    (iv) 단백질 성분 d1은
    a) SARS-CoV-2의 뉴클레오캡시드 인단백질 N과 유사한 서열 번호 2에 따른 서열 또는 서열 번호 2와 적어도 90% 서열 동일성을 갖는 서열; 또는
    b) SARS-CoV-2의 뉴클레오캡시드 인단백질 N과 유사한 서열 번호 26에 따른 서열 또는 서열 번호 26과 적어도 90% 서열 동일성을 갖는 서열
    을 포함하고;
    단백질 성분 d2는 MHV59A의 뉴클레오캡시드 인단백질 N 또는 등가 단백질과 유사한 서열 번호 4에 따른 서열 또는 서열 번호 4와 적어도 90% 서열 동일성을 갖는 서열을 포함하는 것인 백신.
  19. 하기의 연속 단계를 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신의 생산 방법:
    a) 제1항 내지 제9항 중 어느 한 항에 따른 뉴클레오티드 산 서열을 생명공학적 생산 유닛, 특히 세포주에 도입하는 단계로서,
    단백질 성분 a, b1, b2, c1, c2, d1 또는 d2로 이루어진 군으로부터 선택된 단백질 성분 중 적어도 2개를 코딩하는 핵산 기반 mRNA는 번역에 의해 제조되는 것인 단계;
    b) 단계 a)에서 생명공학적 생산 유닛으로부터 단백질 성분을 수득하는 단계; 및
    c) 수득된 단백질 성분을 정제하여 코로나바이러스 SARS-CoV-2에 대한 백신을 수득하는 단계.
  20. 하기의 연속 단계를 포함하는 제16항에 따른 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신의 생산 방법:
    a) 제1항 내지 제9항 중 어느 한 항에 따른 뉴클레오티드 산 서열을 생명공학적 생산 유닛에 도입하는 단계로서, 생명공학적 생산 유닛은 단백질 성분 a, b1, c1 및 d1로 이루어진 군으로부터 선택된 단백질 성분 중 적어도 하나를 코딩하는 뉴클레오티드 산을 포함하는 것인 단계;
    b) 단계 a)에서 생명공학적 생산 유닛으로부터 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 수득하는 단계; 및
    c) 수득된 단백질 성분을 정제하여 제16항에 따른 바이러스 외피, 바이러스 외피의 단편 및/또는 바이러스 외피 단백질을 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신을 수득하는 단계.
  21. 하기의 연속 단계를 포함하는 코로나바이러스 SARS-CoV-2에 대한 백신의 생산 방법:
    a) 제10항 내지 제12항 중 어느 한 항에 따른 벡터를 증폭 생명공학적 생산 유닛에 도입하는 단계;
    b) 증폭 생명공학적 생산 유닛에서 제1항 내지 제9항 중 어느 한 항에 따른 뉴클레오티드 산을 증폭하는 단계;
    c) 단계 b)에서 증폭된 뉴클레오티드 산을 수득하는 단계;
    d) 제19항 또는 제20항에 따른 방법을 사용하여 코로나바이러스 SARS-CoV-2에 대한 백신을 수득하는 단계.
KR1020227033430A 2020-03-03 2021-03-03 코로나바이러스를 방지하는 백신 생산을 위한 완전 합성 장쇄 핵산 KR20220150323A (ko)

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