SUMMARY
Polymersomes are a type of nanoscale vesicle made from block copolymers and can encapsulate a variety of therapeutic agents including proteins and nucleic acids. These nanovesicles are assembled at room temperature and incorporate features such as permanently charged moieties for stability and mannosylation for targeted delivery.
The Unmet Need: A versatile platform that can deliver both RNA and protein payloads in vivo
- Advancements in nanomedicine have allowed researchers to develop biomacromolecular therapies more efficiently and with greater precision, both considering small-interfering RNA (siRNA) therapy, messenger RNA (mRNA) therapies including vaccines, and protein therapies including vaccines and inverse vaccines. However, effective payload protection and delivery are key requirements, as these macromolecules are highly sensitive to clearance and degradation when administered in vivo.
-
Lipid nanoparticle (LNP) technology has successfully demonstrated intravenous delivery of siRNA for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in the liver using the RNA interference (RNAi) pathway. However, issues with storage stability and complex processing limit access to these novel therapies and necessitates improvements in formulation. Furthermore, LNPs are highly specialized for nucleic acid delivery, and therefore no formulations exist for protein payloads, e.g., use as subunit vaccines.
-
Polymer nanoparticles have long been considered a key alternative to LNPs as the macromolecular nature of their substituents impart greater stability and tunability. Their synthetic versatility is particularly attractive for achieving delivery of a wide range of payloads such as proteins, small molecules and nucleic acids, namely mRNA and siRNA. By broadening the type of possible payloads that can be delivered in particulate formulations, a single encapsulation technology could be applicable in a variety of treatments, such as vaccination, tolerization, RNAi therapy, and cancer treatment.
The Proposed Solution: A polymersome platform that addresses several challenges to broad translation of biologic nanoparticle delivery, including scalability, loading efficiency, quality control, and dry storage.
- The faculty inventor developed a novel, highly efficient approach to forming 100 nm vesicular polymer nanoparticles (polymersomes) that requires no organic solvents. As the solution is raised to room temperature, thermally responsive block copolymers self-assemble in aqueous media from unimers. This is possible by using block copolymers with a domain that has a lower critical solution temperature such that they are soluble in aqueous medium under standard refrigeration (4-7°C) temperature, but assemble upon warming to room temperature. The result is large batches of nanoparticles with predictable size and morphology as dictated by polymer structure.
-
The nanomaterials are designed with charged and biofunctional moieties to drive payload affinity as well as in-vivo targeting, respectively. Both siRNA and protein payloads can be incorporated during warming at higher than 75% loading efficiencies. The system is capable of in-vivo delivery in the contexts of protein subunit vaccination, prophylactic immune tolerance induction, and siRNA interference therapy in cancer.
-
Payload-polymer suspensions can also be lyophilized into a dry state, allowing for greater hydrolytic stability under mild (4-7°C) refrigeration conditions, greatly reducing processing and storage requirements.
FIGURE
ADVANTAGES
ADVANTAGES
-
Enhanced stability ensuring the protection and integrity of therapeutic agents until they reach their target
-
Efficient targeting
-
Reduced immune response due to use of biocompatible synthetic polymers
-
Cost-effective scalability
-
Controlled release
APPLICATIONS
- Gene therapy
- Oncology
- Infectious disease
- Vaccine development
- Regenerative medicince
January 10, 2025
Proof of concept
Patent Pending
Licensing,Co-development
Jeffrey Hubbell