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[BioS 레터]'Oligonucleotide 치료제' 전달기술의 발전 - 바이오스펙테이터

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[BioS 레터]'Oligonucleotide 치료제' 전달기술의 발전

입력 2020-10-07 10:27 수정 2020-10-13 09:11

이의정 객원연구원

이 기사는 '프리미엄 뉴스서비스 BioS+' 기사입니다.
미국 FDA 승인받은 치료제들과 개발현황, 그리고 개발에 이용된 기술

올리고뉴클레오타이드(oligonucleotide)는 핵산 중합체(nucleic acid polymers)로, 이를 이용한 치료제는 유전자 발현을 조절하는 혁신적인 기술과 함께 차세대 약품으로 엄청난 잠재력을 보이고 있다. 올리고뉴클레오타이드는 타깃 유전자를 선택적으로 표적화하도록 설계될 수 있기 때문에 정밀의학(Precision medicine)을 가능하게 하는데, 예를 들어 난치 질환 환자가 가진 SNP와 같은 특정 대립 유전자와 같은 특이적 서열들을 표적하는 치료제를 고안할 수 있다. 대부분의 올리고뉴클레오타이드 치료제는 유전자 침묵(gene silencing)에 초점을 맞추고 있지만, 스플라이스 조절(splice modulation)과 유전자 활성화를 포함한 다른 전략들도 활발히 연구 진행중이다.

이 치료제 개발에 있어서 가장 중요한 것은 효과적으로 약을 전달할 수 있는 기술 개발이다. 올리고뉴클레오타이드는 전형적으로 크고 친수성 다가 음이온(polyanion)이며, 이는 그들이 세포막(plasma membrane)을 쉽게 통과하지 못한다는 것을 의미한다. 현재까지, 대부분의 올리고뉴클레오타이드 치료제 혹은 승인된 대부분의 핵산 약물은 국소적 전달(예: 눈이나 척수)이거나 간으로의 전달에 집중되어 있었다. 하지만, 간 이외의 전신 전달을 위한 효과적인 기술 개발은 올리고뉴클레오타이드 치료제 분야의 주요 목표로 남아 있다.

우선, 올리고뉴클레오타이드 치료제에 이용된 기술들을 정리해 보자면 다음 4가지의 기술이 연구개발 중에 있다. 현재 임상실험을 거치고 상용화 된 기술은 Antisense oligonucleotides와 RNA interference 기술이다.

Antisense oligonucleotides...

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