SIRT6 Overexpression Therapy — Gene Therapy & Genetic Interventions
Gene therapy overexpressing sirtuin 6 to enhance DNA repair, metabolic regulation, and lifespan extension.
Overview
SIRT6 is a chromatin-associated NAD+-dependent deacetylase critical for genomic stability, telomere maintenance, and metabolic regulation. SIRT6 overexpression in mice extends median lifespan by 15-27% (sex-dependent). SIRT6 knockout mice exhibit severe progeria. Genflow Biosciences is developing AAV-SIRT6 gene therapy (GF-1002) with preclinical data showing reversal of age-related phenotypes. SIRT6 also suppresses LINE-1 retrotransposon activation, a driver of age-related sterile inflammation.
Indications
- Longevity and healthspan extension
- Genomic instability and DNA repair enhancement
- Metabolic syndrome and glucose homeostasis
- Age-related neurodegeneration (preclinical)
- Cancer prevention via tumor suppression
Mechanism of Action
SIRT6 deacetylates H3K9ac and H3K56ac, promoting heterochromatin formation and genomic stability
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| AAV-SIRT6 (GF-1002) | 1 x 10^12 - 10^13 vg/kg | Single infusion | Genflow Biosciences preclinical program |
Evidence Grade
GRADE D
Safety & Contraindications
- SIRT6 overexpression may sensitize cells to certain chemotherapeutic agents
- Effects on immune function require characterization
- AAV vector immunogenicity and dose-dependent toxicity
- No human clinical trial data available
- Genflow Biosciences (GF-1002) is in preclinical/IND-enabling studies