Gene therapy and its applications

Abstract

Gene therapy is the treatment of abnormal or mutated genes present in cells through the addition of healthy genes or replacement/deletion/site-specific modification of faulty genes. Deoxyribonucleic acid, messenger ribonucleic acid (RNA), small interference RNA, microsomal RNA and antisense oligonucleotides are the genetic materials implicated in gene therapy. They are inserted into the diseased cells using viral or non-viral vectors through an in vivo or ex vivo transduction. Gamma retrovirus, lentivirus, herpesvirus, adenovirus and adeno-associated virus are common viral vectors, while transposons, cationic polymers, dendrimers and cell-penetrating peptides or liposomes are common non-viral vectors. Allologous or autologous T cells, haematopoietic stem cells and chimeric antigen receptor T cells are used for ex vivo gene transduction. Conventional gene therapy of inserting new genetic material shows toxicity such as off-target effects, altered immune responses, inflammatory reactions and possible oncogenic transformation in the recipient. Newer gene editing techniques such as zinc-finger nuclease, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats allow the site-specific correction or control of expression of mutated genes present in cells. Until August 2020, 23 gene-based medicines received approval from drug regulatory agencies in various countries and 362 were in development. Single-gene disorders have shown encouraging results, but evidence of using gene therapy in polygenic and common age-related diseases is still required. Recently, the horizon of gene therapy widened to include COVID vaccines and as an adjunct to chemotherapy. If we could overcome its limitations such as immunogenicity, mutagenicity and high costs, gene therapy can be the medicine of the next generation.