Person:
Yan, Winston

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Yan

First Name

Winston

Name

Yan, Winston

Filters

2015 - 20162

Settings

Author's Publications: search.filters.isAuthorOfPublication.57abb040-76af-4438-888a-1274048925f2

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    In vivo genome editing using Staphylococcus aureus Cas9
    (2015) Ran, F. Ann; Cong, Le; Yan, Winston; Scott, David A.; Gootenberg, Jonathan; Kriz, Andrea J.; Zetsche, Bernd; Shalem, Ophir; Wu, Xuebing; Makarova, Kira S.; Koonin, Eugene; Sharp, Phillip A.; Zhang, Feng
    The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that employ the highly versatile adeno-associated virus (AAV) delivery vehicle. Here, we characterize six smaller Cas9 orthologs and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being >1kb shorter. We packaged SaCas9 and its sgRNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection, we observed >40% gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol levels. We further demonstrate the power of using BLESS to assess the genome-wide targeting specificity of SaCas9 and SpCas9, and show that SaCas9 can mediate genome editing in vivo with high specificity.
  • No Thumbnail Available
    Publication
    In Vivo Gene Editing in Dystrophic Mouse Muscle and Muscle Stem Cells
    (American Association for the Advancement of Science (AAAS), 2016-01-22) Tabebordbar, Mohammadsharif; Zhu, Kexian; Cheng, Jason K. W.; Chew, Wei Leong; Widrick, Jeffrey; Yan, Winston; Maesner, Claire; Wu, Elizabeth Y.; Xiao, Ru; Ran, F. Ann; Cong, Le; Zhang, Feng; Vandenberghe, Luk; Church, George; Wagers, Amy
    Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated but still functional protein. In this study, we develop and test a direct gene editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored Dystrophin reading frame in myofibers, cardiomyocytes and muscle stem cells following local or systemic delivery. AAV-Dmd CRISPR-treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.