Our pipeline includes candidate therapeutics for dry AMD based on gene therapy and epigenetic approaches. Longer term programs target ELOVL2 gene therapy for other aging-related disorders.
Rescue From Age-Related Loss of ELOVL2
Our strategy is to slow cellular senescense in macular degeneration and other age related disorders by “turning back the clock” to a more youthful level of ELOVL2 expression. Our therapeutics are based on:
Supplement ELOVL2 expression by adding additional copies of the gene to photoreceptor and RPE cells.
Increase endogenous ELOVL2 expression via demethylation using intravitreal decitabine microparticles.
ELOVL2 Retinal Gene Therapy: Suprachoroidal and Subretinal Administration
Visgenx has developed proprietary ELOVL2 gene constructs that are well tolerated and express in the targeted cells in the eye (photoreceptors and RPE).
Studies in aged mice have demonstrated a single subretinal administration resulted in:
- Enhanced photoreceptor and Muller cell function
- Protection from aging induced photoreceptor loss
Epigenetic Therapy: Restore Endogeneous ELOVL2 Expression by Demethylation
Visgenx has developed proprietary decitabine microparticles for demethylating hypermethylated ELOVL2 gene promoters to rescue ELOVL2 expression in photoreceptors and RPE.
Preliminary non clinical studies suggest single and repeat intravitreal administration of our proprietary decitabine microparticles is well tolerated and increases the levels of the targeted lipids in the retina.
Non-viral ELOVL2 Gene Therapy
As part of our ELOVL2 gene therapy program, Visgenx is developing unique best in class fully synthetic vector constructs that overcome many of the limitations of viral vectors. Advantages of our synthetic vector constructs include:
- The ability to deliver very large transgenes, much larger than current viral vectors
- Durable and robust transgene expression comparable to viral vectors
- Anti-TLR9 technology
- Eliminates rate limiting step of second strand synthesis as vectors are dsDNA
- Unaffected by pre-existing neutralizing anti-capsid antibodies
- Substantially less immunogenic as there is no protein component within the system
- No Intrinsic ITR promoter (A/D sequence) activity
- Reduced CpG signature
- Sequence not constrained by packaging signal sequences
- Significantly lower cost of goods, totally synthetic-no eukaryotic cells required in manufacturing
Synthetic AAV: CMV-GFP Expression Kinetics in HeLa Cells
Synthetic AAV-ABCA4 for Stargardt’s Disease Contains an 8.9 Kb Payload
Non-Viral Non-Nuclease Based Gene Editing Using Synthetic AAV as a Homologous Donor for Gene Correction/Addition
Example: GFP placed at ALB locus in HepG2 cells resulting in stably integrated GFP under control of ALB gene locus
Mission In Focus.
Learn more about our goal to develop ELOVL2 based therapeutics to slow or halt aging-related disorders.