Session: PMSE/POLY Poster Session:

Amphiphilic Charged Transporters, or ACTs, are block cooligomers with a lipophilic block and a cationic, poly(α-amino ester) block capable of complexing with anionic, oligo- and poly-nucleotides. These oligomers are synthesized via organocatalytic ring-opening polymerization, which enables the synthesis of ACTs with targeted degrees of polymerization, narrow molecular weight distributions, and controlled numbers of cationic monomer units that can rearrange and degrade at physiological pH to form neutral products. Amphiphilic charged transporters (ACT) comprised of a lipophilic block and a polycationic block have been shown to efficiently complex, protect, and deliver poly- and oligo-nucleotides such as small interfering RNA (siRNA) and messenger RNA (mRNA).
ACTs are also relatively unique from a fundamental standpoint because they are lipophilic-cationic block cooligomers instead of the hydrophilic-cationic block copolymers that are commonly used, and because the presence of the lipophilic block is required for successful delivery. ACT/mRNA complexes were previously shown to efficiently induce expression of different mRNAs in both cultured cells and animals, but their fundamental physical structure has yet to be determined. Using transfer RNA (tRNA) as a model polynucleotide, we will show new small-angle neutron scattering, light scattering, and cryogenic transmission electron microscopy results that characterize the solution structure of ACT-tRNA complexes after they have formed, and after they have evolved, at multiple different charge ratios.

Robert Waymouth

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