Delivery systems for gene therapy

Abstract

The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

A review of genetic engineering biotechnologies for enhanced chronic wound healing

“…In terms of usage, adenovirus (ADV) has been the most widely used viral vector in chronic wound‐healing animal experimentation research (see Table S1 for a listing of animal experimentation research with Viral Transduction and Non‐Viral Transfection). Some of the attractive elements of ADV that have fuelled its use include the following: transduction rates of 70‐80% in fibroblasts and keratinocytes, transient expression, no insertional mutagenesis and the ability to infect target cells regardless of cell cycle stage . Because the intent of the therapy is to not to necessarily permanently change the wound bed but to facilitate progression out of a stalled repair state, these features of ADV have been viewed as highly favourable features.…”

“…Because of the limitations associated with ADV, researchers have explored cutaneous transduction with other viruses (ie adeno‐associated virus, retroviruses), unfortunately with a similar pattern of mixed results. Adeno‐associated virus (AAV), a mechanistically similar virus to ADV, has several desirable characteristics which include the following: high particle stability (particularly resistant to heat inactivation), low immunogenicity, able to target non‐proliferating cells, mostly non‐pathogenic to humans and have broad tissue tropism which can be enhanced by engineering capsid proteins . Again, though, AAV has several limiting features that make usage in wound therapy a challenge and include the following: requires high multiplicity of infection (MOI) to transduce cells and has a relatively low pay load capacity of 4‐ kb .…”

“…Adeno-associated virus (AAV), a mechanistically similar virus to ADV, has several desirable characteristics which include the following: high particle stability (particularly resistant to heat inactivation), 23 low immunogenicity, 28 able to target non-proliferating cells, 28 mostly non-pathogenic to humans 22 and have broad tissue tropism which can be enhanced by engineering capsid proteins. 22,32,33 Again, though, AAV has several limiting features that make usage in wound therapy a challenge and include the following: requires high multiplicity of infection (MOI) to transduce cells 28 and has a relatively low pay load capacity of 4-kb. 31 Other viruses have been employed to improve upon these barriers experienced by AAV but due to other intrinsic limitations have not been widely used.…”

Peptide‐based supramolecular hydrogels for delivery of biologics

“…Viral vectors were the first and most widely used vehicles to deliver therapeutic genes with high efficiency, but concerns arose due to unwanted issues with pathogenicity, immune response and inflammatory reactions . Therefore, non‐viral vectors (e.g., gene gun, liposomes and particle‐mediated gene transfer) have also been developed as safer alternatives …”

Features and properties of viral and non-viral gene delivery systems towards effective gene therapy

“…Gene therapy carries the enthusiasm of a solution for a wide range of disease and the possibility to bring to an end or to prevent inherited disease like cystic fibrosis and haemophilia, and its use as the likely cure for heart disease, AIDS, and cancer (Katare and Aeri, 2010). The property of selectively targeting defective gene or neoplastic cell has given gene therapy a promising phenomenon for treatment especially in metastatic cancer patients who are often incurable, or a gene implicated diseases (Mali, 2013). Check (2002) reported the development of leukemia like-condition by a patient who received a successful genetic treatment for SCID from a French trial.…”