Splice-Switching Antisense Oligonucleotides as a Targeted Intrinsic Engineering Tool for Generating Armored Redirected T Cells.

ABSTRACT: Modification of specificity of T cells for the use in adoptive transfer (CAR- or TCR-redirected T cells) has revolutionized the therapy of liquid tumors and some infectious diseases. However, several obstacles are still hampering the efficacy of such potent therapy, hence concurrent modification of the function is also required to obtain successful results. Here we show the use of splice-switching antisense oligonucleotides (SSOs) as a tool to transiently modify T cell function. We demonstrate the possibility to transfect SSOs and an exogenous TCR into primary human T cells in the same electroporation reaction, without affecting viability and function of the transfected T lymphocytes. Moreover, we show that SSOs targeting T cell-specific mRNAs induce the skipping of the targeted exons, and

SUBMITTER: Ceccarello E 

PROVIDER: S-EPMC7997720 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature