Poly(β-amino ester) polymer library with monomer variation for mRNA delivery

Area of Science:

• Biotechnology
• Materials Science
• Immunology

Background:

• Non-viral vectors like lipid nanoparticles (LNPs) are crucial for mRNA delivery.
• LNPs can cause adverse immune responses and off-target effects, necessitating alternative delivery systems.

Purpose of the Study:

• To explore poly(β-amino ester) (PBAE) polymers as an alternative to LNPs for mRNA delivery.
• To evaluate the mRNA delivery efficiency, biodistribution, and immunogenicity of PBAE-based polymer nanoparticles (PNPs).

Main Methods:

• A library of PBAE polymers was synthesized by combining amine and acrylate monomers.
• Polymer nanoparticles (PNPs) were formulated and screened for mRNA delivery efficiency and expression duration.
• Biodistribution, liver toxicity, T-cell immune activation, and neutralization assays were performed.

Main Results:

• Identified PNPs demonstrated high mRNA expression efficiency and sustained expression for up to two weeks.
• PNPs exhibited localized expression at the injection site, with no observed liver toxicity.
• PNPs significantly induced T-cell immune activation and were effective in plaque reduction neutralization tests.

Conclusions:

• PBAE-based PNPs represent a promising alternative to LNPs for mRNA delivery.
• These PNPs show potential for development into mRNA vaccines and therapeutic applications due to their safety and efficacy profile.