CRISPR-Cas9系統是一套高效率基因改造技術平台,對於基因研究應用在人類細胞、動物和植物帶來突破性大變革。此系統的重要核心Cas9核酸內切酶是利用短片段guide RNA辨識目標DNA序列,並切割DNA造成雙股斷裂。藉由 Cas9 進行的雙股DNA 切割,使基因體定㸃斷裂,進而啟動細胞修補機制。CRISPR-Cas9技術不僅能達成定㸃基因剔除, 剔入和基因修飾的目的,也開啟基因治療的契機。我們實驗室將發展更具有效率、精確和安全的CRISPR-Cas9系統,應用於人類基因組編輯。目前,我們的研究方向分為下列幾項:
A robust platform for expansion and genome editing of primary human natural killer cells.
Huang RS, Lai MC, Shih HA, Lin S*
J Exp Med. (2021)
Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection.
Huang KY, Lin MS, Kuo TC, Chen CL, Lin CC, Chou YC, Chao TL, Pang YH, Kao HC, Huang RS, Lin S, Chang SY, Yang PC
EMBO Mol Med. (2021)
Hsc70/Stub1 promotes the removal of individual oxidatively stressed peroxisomes.
Chen BH, Chang YJ, Lin S, Yang WY
Nat Commun. (2020)
A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo.
Chien JC, Tabet E, Pinkham K, da Hora CC, Chang JC, Lin S, Badr CE, Lai CP
Nucleic acids research (2020)
Enhanced NK-92 Cytotoxicity by CRISPR Genome Engineering Using Cas9 Ribonucleoproteins.
Huang RS, Shih HA, Lai MC, Chang YJ, Lin S*
Frontiers in Immunology (2020)
Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.
Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA & Marson A
Proc. Natl. Acad. Sci. USA (2015)
Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery.
Lin S, Staahl B & Doudna JA
eLIFE (2014)
High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity.
Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA & Liu DR
Nat. Biotechnol. (2013)
Structure of the enzyme-ACP substrate gatekeeper complex required for biotin synthesis.
Agarwal V, Lin S, Nair S & Cronan JE
Proc. Natl. Acad. Sci. USA (2012)
Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
Lin S, Hanson RE & Cronan JE
Nat. Chem. Biol. (2010)