Synthetic virology: engineering viruses for gene delivery

Abstract

The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or “bionic” viruses, feature engineered components, or “parts”, that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man-made polymers or inorganic nanoparticles). Various design strategies – rational, combinatorial, and pseudo-rational – have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss-cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavours will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine.

Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

“…The structure of the virus can be tweaked by point mutations, or the virus can incorporate small molecules, synthetic polymers and inorganic nanoparticles. 333 For example, lentiviral vectors are typically pseudotyped with glycoprotein G from vesicular stomatitis virus (VSV-G), extending the vector tropism to a wide range of host cells. 334 By controlling the ratio of assembled wild-type viral capsid to protease-activatable subunits, the overall transduction level of protease-activatable viruses (PAVs) increased.…”

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

“…A number of mammalian viral vectors are under development for gene therapy [2,3]. Glybera, a viral vector derived from adeno-associated virus (AAV) was the first gene therapy approved for clinical use in Europe in 2012 for the treatment of lipoprotein lipase deficiency [4].…”

Virus-Based Nanoparticles as Versatile Nanomachines

“…The internal and external surfaces, coat protein interfaces, and interior cavity are all amenable to functionalization with medically relevant cargos. Mammalian viruses have been investigated in detail for gene delivery applications (3), with numerous VLP and VNP systems undergoing clinical development and several already on the market, including the HPV vaccine Gardasil (17). Novel approaches in the development pipeline include VNPs used for theranostics and tissue engineering (190).…”

“…Viruses have evolved to interact with specific cellular proteins, deliver their nucleic acid cargo, and hijack the intracellular machinery to produce the components of progeny viruses. These properties have led to the development of VNPs based on mammalian viruses for use in gene therapy, but it is difficult to rule out pathogenic effects resulting from natural virus-host interactions (3–5). In contrast, VNPs based on bacteriophages and plant viruses are regarded as safe because even the fully functional viruses cannot infect humans.…”