Current ex-vivo gene therapy technologies and future developments

Abstract

Ex-vivo gene therapy can entail either the replacement or the addition of genes. In gene addition therapy, a therapeutic gene is inserted directly into the host genome, with the abnormal gene remaining intact. In gene replacement therapy, the genome is modified directly. Homologous recombination technology can be used to perform many of these kinds of gene correction. In the past, gene correction therapy has been hampered by the low efficiency of the recombination event. However, recently engineered zinc finger nucleases (ZFNs) were found to have the ability to successfully stimulate homologous recombination by inducing double-strand breaks at specific DNA sites. Another class of enzyme, the transcription activator-like effector nucleases (TALENs), provides an efficient alternative means to induce specific DNA double-strand at breaks. Meanwhile, newly developed gene correction methods using stem cells and induced pluripotent stem (iPS) cells have made gene therapy more feasible in clinical practice. Cells are taken from patients, harvested, and transformed through induction into stem cells, which have the potential to differentiate into a variety of mature cells types for transplant. Further research is needed to develop gene therapy, which may be used in tandem with embryonic and induced pluripotent stem cell therapy, especially to repair preexisting mutations that may be passed on in iPS cells.