Polymerase Chain Reaction: Applications in Gene and Cell Therapy Studies

Abstract

The rapidly developing fields of gene and cell therapy allow us a platform to repair or replace defective genes or introduce a missing gene. AAV and lentivirus are common viral vectors used in gene therapy to deliver a DNA payload to a tissue of interest. Recently, self-replicating RNA-based vaccines and therapies are also becoming increasingly popular for gene therapy after the success of SARS-CoV-2 vaccines. Cell therapy is the transplantation of human cells without or with ex vivo modification utilizing CAR-T and stem cell technology. Because PCR allows us to detect transgenes with high sensitivity, we can leverage this technology to quantify the efficacy of a therapy and long-term expression in vivo using both qPCR and RT-qPCR, respectively. PCR provides information that is used to justify first in human dose, toxicological evaluations, efficacy through PK/PD relationships, monitor persistency and shedding as well as biomarker and gene expression quantitation. As evaluation of safety endpoints is critical to drug development, PCR is imperative in the field of clinical pharmacology discovery.