Woo-Ram LEE, Ja-Yeong LEE, Dong-Ki CHOI, Aeyung KIM, Jeong-Sun KIM, Myung-Hee KWON, Yong-Sung KIM
언어
영어(ENG)
URL
https://www.earticle.net/Article/A119557
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원문정보
초록
영어
Targeting particular mRNAs has become an excellent approach for the silencing of gene expression. Here, we showed a cell-penetrating antibody (transbody) that specifically hydrolyzes targeted mRNAs in the cellular cytosol and leads to targeted gene silencing. We generated a synthetic library on the yeast surface based on 3D8 VL, which is a cell-penetrating and nucleic acid-hydrolyzing single domain antibody. With the cell-penetrating activity, 3D8 VL into the cytosol of living cells can selectively decrease the amount of target sequence-carrying mRNAs. We selected 3D8 VL variants had higher affinity and greater selective hydrolyzing activity for target ss-DNAs than for off targets in the library by using 18-bp single-stranded (ss)-DNAs as target substrates. In particular, one 3D8 VL variant targeting the Her2 sequence showed more efficient downregulation of Her2 expression than a small-interfering RNA targeting the same Her2 sequence, and the variant caused apoptotic cell death of Her2-overexpressing breast cancer cells. Our results demonstrate that the 3D8 VL variants with cell penetrating, nucleic acid-hydrolyzing activity and sequence-selectivity could degrade target mRNAs in the cytosol, which suggests that they would be potential toolds in anti-cancer, anti-viral therapies.
키워드
Protein engineeringGene silencingTransbodyCatalytic antibodyRNA targeting
저자
Woo-Ram LEE [ Dept. of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea. ]
Ja-Yeong LEE [ Dept. of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea. ]
Dong-Ki CHOI [ Dept. of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea. ]
Aeyung KIM [ Dept. of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea. ]
Jeong-Sun KIM [ Dept. of Chemistry, Chonnam National University, Gwangju 500-757, Korea. ]
Myung-Hee KWON [ Dept. of Microbiology, Ajou University School of Medicine, Suwon 442-721, Korea. ]
Yong-Sung KIM [ Dept. of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea. ]
한국생물공학회 [The Korean Society for Biotechnology and Bioengineering]
설립연도
1984
분야
공학>생물공학
소개
이 법인은 생물 공학의 발전과 보급에 이바지하고, 회원 상호 간의 연구 협력과 친목을 도모함을 목적으로 한다
1. 생물공학 분야의 발전을 위한 연구 협력
2. 생물공학의 실용화를 촉진시키기 위한 산학 협동
3. 학술연구 발표회, 강연회, 연수회 등 학술활동의 개최
4. 국,영문 학술지,소식지,학술회의 Proceedings 및 학술도서의 발간
5. 생물공학 발전을 위한 정책 건의
6. 기타 국제 교류 등 본 학회의 목적 달성을 위한 제반 활동