%0 Journal Article
%T The paths toward non-viral CAR-T cell manufacturing: A comprehensive review of state-of-the-art methods.
%A Metanat Y
%A Viktor P
%A Amajd A
%A Kaur I
%A Hamed AM
%A Abed Al-Abadi NK
%A Alwan NH
%A Chaitanya MVNL
%A Lakshmaiya N
%A Ghildiyal P
%A Khalaf OM
%A Ciongradi CI
%A Sârbu I
%J Life Sci
%V 348
%N 0
%D 2024 Jul 1
%M 38702027
%F 6.78
%R 10.1016/j.lfs.2024.122683
%X Although CAR-T cell therapy has emerged as a game-changer in cancer immunotherapy several bottlenecks limit its widespread use as a front-line therapy. Current protocols for the production of CAR-T cells rely mainly on the use of lentiviral/retroviral vectors. Nevertheless, according to the safety concerns around the use of viral vectors, there are several regulatory hurdles to their clinical use. Large-scale production of viral vectors under "Current Good Manufacturing Practice" (cGMP) involves rigorous quality control assessments and regulatory requirements that impose exorbitant costs on suppliers and as a result, lead to a significant increase in the cost of treatment. Pursuing an efficient non-viral method for genetic modification of immune cells is a hot topic in cell-based gene therapy. This study aims to investigate the current state-of-the-art in non-viral methods of CAR-T cell manufacturing. In the first part of this study, after reviewing the advantages and disadvantages of the clinical use of viral vectors, different non-viral vectors and the path of their clinical translation are discussed. These vectors include transposons (sleeping beauty, piggyBac, Tol2, and Tc Buster), programmable nucleases (ZFNs, TALENs, and CRISPR/Cas9), mRNA, plasmids, minicircles, and nanoplasmids. Afterward, various methods for efficient delivery of non-viral vectors into the cells are reviewed.