Gene therapy: advances, challenges and perspectives

Abstract

The ability to make site-specific modifications to the human genome has been an objective in medicine since the recognition of the gene as the basic unit of heredity. Thus, gene therapy is understood as the ability of genetic improvement through the correction of altered (mutated) genes or site-specific modifications that target therapeutic treatment. This therapy became possible through the advances of genetics and bioengineering that enabled manipulating vectors for delivery of extrachromosomal material to target cells. One of the main focuses of this technique is the optimization of delivery vehicles (vectors) that are mostly plasmids, nanostructured or viruses. The viruses are more often investigated due to their excellence of invading cells and inserting their genetic material. However, there is great concern regarding exacerbated immune responses and genome manipulation, especially in germ line cells. In vivo studies in in somatic cell showed satisfactory results with approved protocols in clinical trials. These trials have been conducted in the United States, Europe, Australia and China. Recent biotechnological advances, such as induced pluripotent stem cells in patients with liver diseases, chimeric antigen receptor T-cell immunotherapy, and genomic editing by CRISPR/Cas9, are addressed in this review.

Encapsulation, Visualization and Expression of Genes with Biomimetically Mineralized Zeolitic Imidazolate Framework‐8 (ZIF‐8)

“…The efficacy of gene therapy has been greatly affected by the inadequacy of delivery vectors. Over 70% of the gene therapy clinical trials involve viral vectors and only about 11% of trials utilized non‐viral delivery systems . Viral therapy has been most effective for monogenic diseases such as severe combined immune deficiency (ADA‐SCID), in which disease pathogenesis is attributed to a single gene .…”

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

“…In spite of significant efficacy and convenience for some purposes, these methods are not flawless and have obstacles to overcome before application to mitochondria 111 . Viral‐based methods, although demonstrate high transfection efficiency, are prone to initiate host immune response and have a limit in size of delivered genes 112 . CRISPR/Cas9, which is a well‐known method of nuclear genome editing, still remains uncertain for the mitochondrial genome.…”

Designer Nucleases: Gene-Editing Therapies using CCR5 as an Emerging Target in HIV

“…According to Parliamentary Office of Science and Technology, Genome Editing involves manipulating the genetic code at targeted locations within the DNA sequence and has an extensive range of applications in biomedical research, human therapies (somatic-cell therapies that only affect the patient himself or germline therapies that may be inherited by future generations) and even agriculture, which all have prospective benefits for human health. 63,64 The targeted modification of the human genome uses enzymes, particularly nucleases, not only to change individual genetic code bases with the purpose of disabling, repairing or modifying the function of a gene, but also to precisely introduce a new gene, thereby conceding a different function or characteristic to a living cell. 63,65 As reported by the Foundation for AIDS Research (amfAR), an HIV infected person needs to fulfil three main principles to be considered effectively cured: be capable of living a normal and healthy life; persist in the absence of antiretroviral therapy or any other HIV-related medications; and be incapable of transferring the virus to others.…”