HEDGES offers the ability to express one or more therapeutic genes for controlled periods to potentially treat a spectrum of different mono- and polygenic diseases as well as lethal pandemic infections.
Gene therapy is beginning to transform treatment of monogenic-deficiency diseases. However, common viral delivery approaches such as Adeno-associated virus (AAV), have a variety of limitations including restricted gene delivery capacity, vector immunogenicity which prevents AAV re-administration, and manufacturing challenges. DNARx’s gene delivery platform expresses one or more therapeutic genes efficiently, repeatedly, controllably and safely.
HEDGES, DNARx’s nonviral DNA- and liposome-based gene delivery platform, has been shown in animal models to have multiple advantages over current gene delivery platforms:
- LARGE DNA INSERTS.
HEDGES has been shown to efficiently express large DNA inserts containing one or more therapeutic genes. In addition, HEDGES efficiently re-expresses these genes following re-injection in immunocompetent, outbred rodents.
One systemic HEDGES injection produces extended therapeutic levels of a range of cDNA-encoded human protein therapies, including monoclonal antibodies, without detectable integration into genomic DNA. Classical toxicity markers which are elevated with conventional non viral DNA-based approaches are kept at or near background levels with HEDGES.
- CONTROLLABLE EXPRESSION DURATION.
Unlike AAV vectors, the HEDGES platform can be modified to control the duration of gene expression produced after one treatment. Different HEDGES formulations have expressed therapeutic proteins from less than 3 weeks to more than 1.5 years.
EXAMPLES OF HEDGES ADVANTAGES:
- One HEDGES Injection Encoding the Anti-CD20 mAb Rituximab in CD-1 Mice Retains Full Anti-Tumor Activity for >280 days
- HEDGES Allows Control of Duration of hG-CSF Protein Production from <21 to >580 days, Depending on the HEDGES Formulation
- HEDGES Avoids the Host Toxicity Produced by Conventional, Non Viral DNA-Based Gene Delivery Approaches
- HEDGES does not Integrate into Genomic DNA, thus Avoiding Potential Mutagenic and Oncogenic Sequelae
- One HEDGES Injection Encoding Anti-Influenza mAb 5J8 Neutralizes H1N1 Strain for >210 days
Therapeutic serum hG-CSF levels produced by one IV, HEDGES-based vector injection ranged from more than 575 days to less than 21 days. Independent components including DNA vector enhancer-promoter elements and liposome formulation allow for tunable control of duration of expression of the HEDGES platform.
One IV injection of HEDGES produced fully bioactive rituximab levels within 24 hours. These levels persisted for >275 days. Serum expression at timepoints 5-10 months of after HEDGES treatment was measured by an ELISA-based assay.