# Gene Therapy-mediated Angiogenesis to Enhance Survival of Transplanted Fat > **NIH NIH R41** · ENYX THERAPEUTICS, LLC · 2024 · $295,901 ## Abstract Abstract. Autologous fat grafts are widely used for soft tissue reconstruction of congenital deformations, defects caused by traumatic wounds, oncologic surgery, and improving the form and function of skin grafts, scar contractures, radiation damage and a variety of aesthetic applications. The long-term results are often disappointing because of variable and often significant loss of the graft, with clinically observed 1 year resorption rates of up to 70% or more. A major cause of loss of the transplant is inadequate vascularization of the fat following transplantation. Several strategies have been tried to stimulate vascularization of transplanted fat, but none have been translated to human use, likely because the stimuli used to induce angiogenesis are inadequate in potency and/or length of biologic availability. ENYX Therapeutics, an early-stage biotechnology company focused on using in vivo gene therapy technology to treat disorders of unmet medical need, is developing a novel, potent, single administration gene therapy to enhance the survival of autologous fat transplants. The ENYX strategy is to administer ENX02 (Ad5VEGF- All6A+) to the autologous fat ex vivo prior to transplantation, a E1‾E3‾ serotype 5 adenovirus (Ad) vector coding for a genomic hybrid coding for all 3 major isoforms of human vascular endothelial growth factor (VEGF121, 165 and 189). Ad5VEGF-All6A+ is 10 to 100-fold more potent than an Ad coding for any one isoform in inducing angiogenesis. Based on preliminary data demonstrating that Ad5 vectors can effectively genetically modify fat to induce angiogenesis, the hypothesis to be tested is that ENX02 will genetically modify transplanted human fat to express and secrete VEGF 121, 165 and 189, that in turn, will induce functional neovascularization into the transplanted fat from the surrounding tissues, resulting in significantly increased fat transplant survival. In collaboration with the gene therapy expertise of the R. Crystal laboratory, Department of Genetic Medicine and the pre-clinical and clinical expertise in reconstructive surgery and fat transplantation of the J. Spector laboratory, Department of Surgery, all of the technology and infrastructure are in place for assessment of ENX02 to enhance survival of transplanted human fat. This phase 1 STTR will have the following specific aim. Specific aim 1. To demonstrate that administration of ENX02 (Ad5VEGF-All6A+) to harvested human fat prior to transplantation will induce an increased rate and degree of in vivo neovascularization of the transplanted fat from surrounding tissues resulting in significantly increased survival of the transplant in immunodeficient mice. ## Key facts - **NIH application ID:** 10912162 - **Project number:** 1R41HL170928-01A1 - **Recipient organization:** ENYX THERAPEUTICS, LLC - **Principal Investigator:** RONALD G CRYSTAL - **Activity code:** R41 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $295,901 - **Award type:** 1 - **Project period:** 2024-05-01 → 2026-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10912162 ## Citation > US National Institutes of Health, RePORTER application 10912162, Gene Therapy-mediated Angiogenesis to Enhance Survival of Transplanted Fat (1R41HL170928-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10912162. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*