Earticle

초록

영어

Targeting particular mRNAs has become an excellent approach for gene silencing. 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 of the light chain variable domain. With the cell-penetrating activity, 3D8 VL into he 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 single-stranded (ss)-DNAs than for off targets in the library by using 18bp-ssDNAs as target substrates. In particular, one 3D8 VL variant targeting the Her2 sequence showed more efficient downregulation of Her2 expression than a smallinterfering RNA targeting the same 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 tools in anti-cancer or anti-viral therapies.

키워드

저자

• Ja-Yeong LEE [ Dept. of Molecular Science and Technology, Ajou University ]
• Woo-Ram LEE [ Dept. of Molecular Science and Technology, Ajou University ]
• Ji-Young JANG [ Dept. of Microbiology, Ajou University School of Medicine ]
• Jeong-Sun KIM [ Dept. of Chemistry, Chonnam National University ]
• Myung-Hee KWON [ Dept. of Microbiology, Ajou University School of Medicine ]
• Yong-Sung KIM [ Dept. of Molecular Science and Technology, Ajou University ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국생물공학회 학술대회

• 간기

  반년간

• 수록기간

  1985~2013

• 십진분류

  KDC 476 DDC 576