Uncovering the Critical Physiochemical Factors behind Polyelectrolyte Complexation with RNA
ORAL
Abstract
Polyelectrolyte complexes (PECs) are membranelles materials formed from oppositely charged polymers that phase separate from solution. PEC micelles (PCMs) are a class of self-assembled nanoparticles that contain a non-charged polymer component limiting polyelectrolyte complexation to the nanoscale. PCMs show significant promise for nucleic acid (NA) delivery due to their hydrated nature and programmable features. NAs, due to their dense negative charges, are not only sequestered but play an active role in assembly and thus strongly influence the physical properties of polyelectrolyte assemblies. Despite their like charges, DNA and RNA show vast differences in PCM assembly. Specifically, double-stranded (ds) RNA fails to assemble PCMs under the same conditions as dsDNA, which poses an enormous limitation for delivery of short-interfering RNA, which is predominately double-stranded and holds unique advantages for gene targeting and silencing. Through systemic studies of polyelectrolyte properties and assembly mechanisms, and utilizing a combination of small angle x-ray scattering, microscopy, and all-atom molecular dynamic simulations, we are uncovering the molecular forces behind RNA complexation. These studies expand our understanding of biomaterial self-assembly and will direct the design of future NA delivery systems.
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Publication: - Hussain AF*, Keys CK*, Houston JT, Marras AE. Impact of Nucleic Acid Structure and Sequence on Polyelectrolyte Complex Micelle Morphology. (manuscript in process)<br>- Hussain AF, Sansalone JM, Chava BS, Keys CK, Arora AJ, Beshir NH, Aluru NR, Marras, AE. Polyelectrolyte complexation with RNA. (manuscript planned)
Presenters
Aasim F Hussain
University of Texas at Austin
Authors
Aasim F Hussain
University of Texas at Austin
John M Sansalone
University of Texas at Austin
Bhargav S Chava
University of Texas at Austin
Shaun G Newman
Weizmann Institute of Science, Rice University, Wiezmann Institute of Scince, Columbia University, University of Texas at Austin, Los Alamos National Laboratory
Arora J Amrita
University of Texas at Austin
Nour H Beshir
University of Texas at Austin
Narayana R Aluru
The University of Texas at Austin, University of Texas at Austin
