PNA Amphiphile Adjuvant Delivery Vehicles
The current invention of synthetic nanoparticle carrying cyclic dinucleotide (CDN), an immunomodulatory compound, can be used to induce or enhance immune responses with the potential use as adjuvant for vaccines. It can also be used to elicit an immune response against cancer or bacterial infections.
Researchers
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synthetic nanoparticles for delivery of immunomodulatory compounds
United States of America | Granted | 10,300,145 -
synthetic nanoparticles for delivery of immunomodulatory compounds
United States of America | Granted | 11,207,418
Figures
Figure depicts the chemical structure of a peptide nucleic acid (PNA) oligomer containing three guanine bases (G3-PNA) and two lysines designed to form a noncovalent complex with cdGMP and a schematic of the complex.
Figure depicts three exemplary configurations for an amphiphile containing a G3-PNA headgroup and polyethylene glycol (PEG-DPSE) that are designed to noncovalently complex with an immunomodulatory compound, i.e., cdGMP. Schematics of the initial micellar structures formed by the PNA amphiphiles are shown in the middle column and the anticipated nanoparticles formed upon cdGMP complexation are shown in the right column.
Figure is a UV melting curve graph (left) and the first derivative of the UV melting curve (right), confirming the association of cdGMP and G3-PNA.
Figure is a graph showing an increase in luminescence producing in a STING reporter cell line by PNA/PEG-DPSE micelles carrying cdGMP.
Technology
This invention uses PNA oligomer as a carrier of CDN, where they form reversible noncovalent complexes through pi-pi base stacking and hydrogen-bond interactions. The PNA oligomer is covalently conjugated to an amphiphile such as diacyl lipid tail, and optionally may include a polyethylene glycol (PEG) molecule. The arrangement of the lipid tail and PEG molecule allows for modulation of size and structure of the synthetic nanoparticle to control CDN delivery based on the desired response.
Problem Addressed
The role of CDN as an immunomodulatory compound has been demonstrated for a while; however, its use has been limited due to poor pharmacokinetics. Injected CDN is rapidly flushed from the site of injection, leading to systemic inflammation. Thus, there is a need for CDN delivery methods that retain the compound at the site of injection. The current invention utilizes synthetic nanoparticles formed by mixing CDN with peptide nucleic acid (PNA)-amphiphile conjugate to increase retention at the site of injection and avoid systemic inflammatory effects.
Advantages
- PNA-amphiphile conjugate acts as a modulatable carrier of CDN to control delivery and reduce systemic inflammatory effects.
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