Coxsackievirus B3 used as a gene therapy vector to express functional FGF2

Area of Science:

• Molecular Biology
• Virology
• Biotechnology

Background:

• Current gene therapies rely on limited viral vectors, hindering progress.
• Developing novel recombinant vectors is crucial for advancing gene therapy applications.

Purpose of the Study:

• To investigate coxsackievirus B3 (CVB3) as a novel recombinant vector for gene delivery and expression.
• To assess the therapeutic potential of CVB3-mediated gene delivery in vivo.

Main Methods:

• Constructed a recombinant CVB3 complementary DNA (cDNA) encoding human fibroblast growth factor 2 (FGF2).
• Evaluated FGF2 expression in vitro (HeLa cells, cardiomyocytes) and in vivo (mouse hindlimbs).
• Assessed the therapeutic efficacy in a mouse model of ischemic hindlimb injury.

Main Results:

• Recombinant CVB3-FGF2 efficiently expressed FGF2 in various cell types and mouse tissues.
• CVB3-FGF2 injection protected ischemic hindlimbs from necrosis and improved blood flow.
• The virulence of the CVB3 vector was significantly attenuated in the recombinant virus.

Conclusions:

• Coxsackievirus B3 can be modified to express functional foreign proteins, serving as a novel viral vector for gene therapy.
• The attenuated CVB3-FGF2 demonstrates therapeutic potential for ischemic conditions.