Your browser doesn't support javascript.
loading
Evaluation of the Elements of Short Hairpin RNAs in Developing shRNA-Containing CAR T Cells.
Urak, Ryan; Gittins, Brenna; Soemardy, Citradewi; Grepo, Nicole; Goldberg, Lior; Maker, Madeleine; Shevchenko, Galina; Davis, Alicia; Li, Shirley; Scott, Tristan; Morris, Kevin V; Forman, Stephen J; Wang, Xiuli.
Afiliação
  • Urak R; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Gittins B; Center for Gene Therapy, Beckman Research Institute, Duarte, CA 91010, USA.
  • Soemardy C; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Grepo N; Center for Gene Therapy, Beckman Research Institute, Duarte, CA 91010, USA.
  • Goldberg L; Center for Gene Therapy, Beckman Research Institute, Duarte, CA 91010, USA.
  • Maker M; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Shevchenko G; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Davis A; Center for Gene Therapy, Beckman Research Institute, Duarte, CA 91010, USA.
  • Li S; Center for Gene Therapy, Beckman Research Institute, Duarte, CA 91010, USA.
  • Scott T; Center for Gene Therapy, Beckman Research Institute, Duarte, CA 91010, USA.
  • Morris KV; Center for Gene Therapy, Beckman Research Institute, Duarte, CA 91010, USA.
  • Forman SJ; Menzies Health Institute Queensland, School of Pharmacy and Medical Science, Griffith University, Gold Coast Campus, Southport, QLD 4215, Australia.
  • Wang X; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
Cancers (Basel) ; 15(10)2023 May 20.
Article em En | MEDLINE | ID: mdl-37345185
ABSTRACT
Short hairpin RNAs (shRNAs) have emerged as a powerful tool for gene knockdown in various cellular systems, including chimeric antigen receptor (CAR) T cells. However, the elements of shRNAs that are crucial for their efficacy in developing shRNA-containing CAR T cells remain unclear. In this study, we evaluated the impact of different shRNA elements, including promoter strength, orientation, multiple shRNAs, self-targeting, and sense and antisense sequence composition on the knockdown efficiency of the target gene in CAR T cells. Our findings highlight the importance of considering multiple shRNAs and their orientation to achieve effective knockdown. Moreover, we demonstrate that using a strong promoter and avoiding self-targeting can enhance CAR T cell functionality. These results provide a framework for the rational design of CAR T cells with shRNA-mediated knockdown capabilities, which could improve the therapeutic efficacy of CAR T cell-based immunotherapy.
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos