Oisin Biotechnologies Senolytic Gene Therapy — Gene Therapy & Genetic Interventions
Lipid nanoparticle-delivered DNA construct that selectively eliminates senescent cells using p16-driven apoptosis.
Overview
Oisin Biotechnologies (now part of Repair Biotechnologies) developed a senolytic gene therapy platform using lipid nanoparticle-delivered DNA constructs containing a p16INK4a promoter driving an inducible caspase-9 (iCasp9) suicide gene. This system selectively eliminates senescent cells expressing high levels of p16, a key marker and mediator of cellular senescence. In preclinical mouse studies, the therapy reduced senescent cell burden by 50-80%, improved physical function, and extended remaining lifespan by 20% when administered to aged mice. Unlike small-molecule senolytics, this approach provides genetic-level specificity for senescent cells.
Indications
- Senescent cell clearance
- Age-related functional decline
- Idiopathic pulmonary fibrosis (preclinical)
- Osteoarthritis (preclinical)
- Atherosclerotic plaque stabilization (preclinical)
Mechanism of Action
Lipid nanoparticles deliver DNA construct containing p16 promoter-driven inducible caspase-9 to cells throughout the body
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| LNP-p16-iCasp9 construct | Study-specific | Single or repeated treatments | Followed by AP1903 dimerizer to activate apoptosis |
| AP1903/Rimiducid (dimerizer) | 0.4 mg/kg | 24-48 hours post-LNP | Activates iCasp9 only in p16-expressing cells |
Evidence Grade
GRADE D
Safety & Contraindications
- p16 is also expressed in some non-senescent cells (e.g., pancreatic beta cells, macrophages)
- Excessive senescent cell clearance may impair wound healing and tissue remodeling
- LNP delivery may cause transient inflammation and liver accumulation
- Caspase-9 dimerizer drug (AP1903/rimiducid) required for activation
- No human clinical trials initiated
- Long-term effects of repeated senescent cell clearance unknown