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348 Warning: mysql_real_escape_string(): Access denied for user 'et1ssh96'@'localhost' (using password: NO) in /service/web/biospcmbl/comlib/dblib.php on line 30 Warning: mysql_real_escape_string(): A link to the server could not be established in /service/web/biospcmbl/comlib/dblib.php on line 30 Warning: mysql_query(): Access denied for user 'et1ssh96'@'localhost' (using password: NO) in /service/web/biospcmbl/comlib/dblib.php on line 530 Warning: mysql_query(): A link to the server could not be established in /service/web/biospcmbl/comlib/dblib.php on line 530 Warning: mysql_fetch_array() expects parameter 1 to be resource, boolean given in /service/web/biospcmbl/comlib/dblib.php on line 531 유전자치료제, 안전성 논란.."AAV, 원숭이서 심각한 독성" - 바이오스펙테이터

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유전자치료제, 안전성 논란.."AAV, 원숭이서 심각한 독성"

입력 2018-01-31 11:04 수정 2018-01-31 19:05

바이오스펙테이터 이은아 기자

이 기사는 유료회원만 이용할 수 있는 BioS+ 기사입니다.
원숭이, 돼지모델에서 고용량 AAV 유전자치료제에 따른 심각한 독성반응 보여..안전성 논란에 유전자치료 회사 Solid Bio, Avexis 등 관심 집중

▲재조합 AAV9 Capsid Shell (출처: Avexis 홈페이지)

고용량 AAV(Adeno-Associated Virus) 벡터 기반 유전자치료제를 투여받은 원숭이와 돼지에서 심각한 독성을 나타낸다는 연구결과가 발표되면서 유전자치료법의 안전성에 대한 논란이 불거졌다. AAV는 유전자물질을 인위적으로 전달하는 운반체다.

유전자치료의 선구자인 James Wilson 박사와 펜실베이니아대학 연구팀은 희귀 퇴행성 신경질환인 척수성근위축증(SMA, spinal muscular atrophy) 치료를 위해 hSMN 유전자를 발현하는 AAV9 벡터를 원숭이와 돼지에 고용량 정맥(Intravenous, IV) 투여하자 생명을 위협하는 심각한 독성반응을 관찰했다고 발표했다. 이번 연구는 Human Gene Therapy 저널에 30일 온라인 버전으로 공개됐다.

이번 연구는 미국 유전자치료 전문기업 솔리드 바이오사이언스(Solid Biosciences)가 약 2개월 전 FDA로부터 척수성근위측증에 대한 고용량 AAV 유전자치료의 임상시험 신청에 대해 보류 결과를 받은 것과 일치하는 결과다.

논문이 발표되면서 지난 30일 Solid Biosciences의 주식는 약 12% 하락했다. 이번 연구를 이끈 Wilson 박사는 최근 Solid Bio에서 맡고 있던 과학자문위원을 고용량 AAV 벡터 사용의 위험성에 대한 우려를 이유로 사임한 바 있다.

연구진은 운동신경세포에 유전자치료제의 전달 효율성을 평가하기 위해 hSMN 유전자를 발현하는 AAVhu68 벡터를 2 X 10^14 GC/kg 용량으로 투여했다. 4일 후 한 원숭이(14개월)는 심각한 간 손상과 쇼크를 보이며 결국 안락사 됐다. 두 마리의 다른 원숭이 역시 심각한 독성반응이 나타났다. 이러한 독성 이상반응은 기존의 다른 AAV 벡터에서 나타났던 것처럼 벡터 캡시드(vectro capsid)와 전이유전자(transgene)에 따른 T세포 면역반응과는 관련성이 없다고 밝혔다.

유사한 용량으로 전신 IV 투여받은 돼지(7~30일) 3마리도 운동실조(ataxia) 상태와 신경증상 등의 이상반응을 보였고, 결국 투여받은지 14일 이내 안락사됐다. 이러한 부작용 증상이 면역반응과는 무관하게 고용량 AAV 도입에 따른 직접적인 결과로 보인다는 것...

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