Description:
INV-17107
Background
Oligonucleotides (ONs) are considered a form of informational drug, where drug-like properties (pharmacophore) and target information (dianophore) are independent of each other. ON therapeutics would enhance new drug development but ONs are underutilized due to enzymatic degradation, poor cellular uptake, rapid liver clearance, unwanted activation of the immune system, and overall low efficacy. Despite various chemical modifications and use of vectors (viral, liposomal) of ONs the drawbacks including toxicity, immunogenicity, and instability remain. To combat these drawbacks researchers have put forward a robust new class of nucleic acid-based micellar nanoparticles.
Technology Overview
Northeastern researchers have designed novel nucleic acid-based micellar nanoparticle for the delivery of antisense gene to the targeted DNA. The micelles are co-assembled from two amphiphilic diblock copolymers DNA-bpoly(ɛ-caprolactone) (DNA-b-PCL), PEG-b-PCL, and PCL homopolymer. By screening a library of micelle compositions, researchers have revealed a series of structure-property relationships. DNA hybridization availability and enzyme shielding are affected by the molecular weight of the PEG block and the surface PEG density. These parameters also effect cellular uptake, with PEG-dominated surfaces showing moderate uptake and DNA-dominated surfaces showing high uptake.
Consisting of biodegradable and biocompatible components, these DNA block copolymer micelles represent an important departure from cationic systems which have been exhaustively investigated as nucleic acid delivery vectors. This micellar system shows resistance against enzymatic degradation, higher stability, and lower immunogenicity.
Benefits
- Enhanced nuclease stability of antisense gene
- Enhanced cell uptake
- Targeted drug delivery with reduced side effects
- Minimal cytotoxicity
- Reduced immunogenicity
Applications
- Delivery of other biomolecules: siRNA, microRNA, and peptides
- Effective antisense gene regulation
- Oligonucleotide-based therapeutics and diagnostic agents
Opportunity
- License
- Partnering
- Research collaboration