Gene therapy by virus-like self-spooling toroidal DNA condensates for revascularization of hindlimb ischemia

• DOI: 10.1186/s12951-024-02620-3
• Publication Date: 2024-07-15T02:01:55Z
• Authors: Yue Wang; Jun Liu; Changgui Tong; Lei Li; Hongyang Cui; Liuwei Zhang; Ming Zhang; Shijia Zhang; Kehui Zhou; Xiabin Lan; Qixian Chen; Yan Zhao
• Keywords: Therapeutic angiogenesis; Polylysine; Hindlimb

Peripheral arterial diseases (PAD) have been reported to be the leading cause for limb amputations, and current therapeutic strategies including antiplatelet medication or intervene surgery are not clinically benefit patients with high-grade PAD. To this respect, revascularization based on angiogenetic vascular endothelial growth factor (VEGF) gene therapy was attempted potential treatment of critical Aiming transcellular delivery VEGF-encoding plasmid DNA (pDNA), we proposed elaborate intriguing virus-like condensates, wherein supercoiled rigid micrometer-scaled (pDNA) could regulated in an orderly fashion into well-defined nano-toroids by following a self-spooling process aid cationic block copolymer poly(ethylene glycol)-polylysine at extraordinary ionic strength (NaCl: 600 mM). Moreover, reversible disulfide crosslinking between polylysine segments aim stabilizing these toroidal condensates. Pertaining hindlimb ischemia, our pDNA condensates demonstrated high levels VEGF expression dosage sites, which consequently contributed neo-vasculature (the particularly abundant formation micro-vessels injected hindlimb), preventing ischemia from causing necrosis extremities. excellent safety profiles as opposed apparent immunogenicity naked pDNA. Hence, herald potentials platform persistent expressions proteins, might highlighted management variety intractable diseases.