Charge neutralized poly(β-amino ester) polyplex nanoparticles for delivery of self-amplifying RNA.

ABSTRACT: Therapeutic self-amplifying RNA (saRNA) is a promising approach for disease treatment, as it can be administered in lower doses than messenger RNA (mRNA) to achieve comparable protein production levels. However, saRNA requires an appropriate delivery vehicle to protect it during transit and facilitate its transfection. A widely-adopted approach has been to use polycations to condense these large anionic macromolecules into polyplex nanoparticles, however their high charge density often elicits cytotoxic effects. In this study we postulated that we could improve the potency and tolerability of such delivery vehicles by co-formulating poly(β-amino ester)s saRNA polyplexes with a non-toxic anionic polymer, γ-polyglutamic acid (γ-PGA) to neutralize partially this positive charge. Accordingly,

SUBMITTER: Dastgerdi NK 

PROVIDER: S-EPMC10898429 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature