상세 보기
- Lee, Byung-Chul;
- Gin, Ashley;
- Wu, Chuanfeng;
- Singh, Komudi;
- Grice, Max;
- 외 10명
WEB OF SCIENCE
19SCOPUS
18초록
For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDR-edited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via p53 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs. © 2024 Elsevier Inc.
키워드
- 제목
- Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques
- 저자
- Lee, Byung-Chul; Gin, Ashley; Wu, Chuanfeng; Singh, Komudi; Grice, Max; Mortlock, Ryland; Abraham, Diana; Fan, Xing; Zhou, Yifan; AlJanahi, Aisha; Choi, Uimook; DeRavin, Suk See; Shin, Taehoon; Hong, Sogun; Dunbar, Cynthia E.
- 발행일
- 2024-04
- 유형
- Article
- 저널명
- Cell Stem Cell
- 권
- 31
- 호
- 4
- 페이지
- 455 ~ 466