Abstract: Objective To evaluate the safety and preliminary therapeutic efficacy of intramuscular injection of SeV-hFGF2/dF (BF30), a viral vector carrying the hFGF2 gene, in patients with peripheral arterial disease (PAD). Methods Twelve male PAD patients, aged(48±13) years(range: 28-66 years), were enrolled. Rutherford classifications were as follows: stage 2(n=1, 8.3%), stage 3(n=1, 8.3%), stage 4(n=3, 25%), and stage 5(n=7, 66.7%). All patients were ineligible for or unlikely to benefit from surgical intervention and received varying doses of BF30 via intramuscular injection in the affected limb based on enrollment order. Adverse events were monitored during follow-up and viral genome concentration, angiogenic factors, pro-inflammatory cytokines, and anti-drug antibody levels were measured. Therapeutic efficacy was preliminarily evaluated using pain scores, ankle-brachial index (ABI), Rutherford classification, and quality-of-life scales. Results During the 6-month follow-up, no severe adverse events or grade 3/4 adverse reactions related to BF30 injections were observed. Viral genome levels in all subjects were below the detection limit, with seven cases testing negative in hemagglutination assays. Serum levels of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and pro-inflammatory cytokines showed no significant changes from baseline. Anti-drug antibodies were undetectable in all participants. patients exhibited significant alleviation of resting pain(P＜0.05). Conclusions Intramuscular injection of SeV-hFGF2/dF demonstrates favorable safety in PAD patients, though further studies are needed to confirm efficacy.

Key words: chronic limb-threatening ischemia, human fibroblast growth factor 2, safety, gene therapy