Genetic engineering strategies for cell-based therapy: viral, non-viral, and precision genome editing technologies

Abstract

Objective: To review the existing genetic engineering strategies commonly used for generating chimeric antigen receptor (CAR)-T cell therapy. Methods: This article provides a comprehensive literature review and compares different approaches on viral, non-viral and precision genome editing technologies, aiming to provide an overview and guidelines for methods selection during clinical CAR-T cell manufacturing. Results: CAR-T cell therapy has revolutionized cancer treatment for hematological malignancies. The manufacturing of CAR-T cell therapy relies on the genetic modification of T cells to achieve ectopic CAR gene expression. Depending on the evolving CAR designs, viral, non-viral, and genome editing platforms are used for optimal CAR expression, which could determine the clinical efficacy and safety profiles of these products. Efforts have been ongoing to empower CAR-T cell efficacy while minimizing toxicity over the past decades. Conclusion: Successful CAR-T cell therapy depends on rational platform selection and optimization of gene delivery methods based on clinical needs and context.