Progress and problems with the use of viral vectors for gene therapy

Abstract

Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

“…However, there are potential risks and limitations associated with gene therapy, and the clinical application of protein therapy has been hampered by the lack of effective vehicles and issues with protein production [132–134]. For example, the viral vectors commonly used in gene therapy can trigger immune responses and may have off-target effects on other cells [135,136]. Moreover, despite a great deal of research effort, we largely lack an effective method to deliver membrane proteins to specific membrane environments.…”

Genetically engineered Sertoli cells are able to survive allogeneic transplantation

“…Most notable are the recent reports identifying the negative issues using adenoviral vectors as a means of inserting genes into cells. 22,27 Other vectors have had similar unacceptable safety profiles, 21,22 not to mention that the current vectors are limited as to the size of the gene constructs and hence, the types of proteins that can be generated.…”

“…Traditionally, these therapies have involved the use of viral vectors or other methods to produce the expression (often transient) of the gene of interest, raising questions of safety and efficacy. [20][21][22] Cell-based gene therapy has been proposed as one means of overcoming these issues but has itself been hampered by the lack of an abundant, safe and immunologically acceptable source of the tissue. 21 Theoretically, transgenic animals can be designed to produce specific therapeutic proteins overcoming the issues of transient expression and safety associated with viral vectors, but this is hampered by immune rejection of the allogeneic or xenogeneic tissue.…”

Cells as vehicles for therapeutic genes to treat liver diseases

“…In the former case, a systemic inflammatory reaction (which may be lethal) can occur and in the latter case, the transduced cells can be eliminated by activated T cells leading to tissue damage and abrogation of transgene expression. 1 On the other side, when the vector is injected directly into the subject, it can stimulate the production of neutralizing antibodies making re-treatment ineffective. 1 In addition, targeting the vector to the desired site is an issue when given systemically.…”

“…1 On the other side, when the vector is injected directly into the subject, it can stimulate the production of neutralizing antibodies making re-treatment ineffective. 1 In addition, targeting the vector to the desired site is an issue when given systemically.…”