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MSL Faculty Candidate Seminar: Dr. Anna Katherine Blakney
January 22, 2020 @ 10:00 am - 11:00 am
The Michael Smith Laboratories presents a faculty candidate seminar:
Dr. Anna Katherine Blakney
Postdoctoral Research Fellow
Imperial College London
Date: Wednesday, January 22nd
Time: 10:00 AM
Location: MSL Auditorium (MSL 102) – 2185 East Mall
Title: Big is beautiful: Enhanced saRNA delivery and immunogenicity by a higher molecular weight, bioreducible, cationic polymer
Abstract: Self-amplifying RNA (saRNA) vaccines are highly advantageous as they result in enhanced protein expression compared to messenger RNA (mRNA), thus minimizing the required dose. Previous delivery strategies have been optimized for small interfering RNA (siRNA) or mRNA, and do not necessarily deliver saRNA efficiently, thus motivating the development and optimization of novel delivery platforms specifically for saRNA. We have engineered a bioreducible, linear, cationic polymer called ‘pABOL’ specifically for saRNA delivery and show that increasing the molecular weight of the polymer enhances delivery both in vitro and in vivo. We demonstrate that pABOL enhances protein expression and cellular uptake via both intramuscular and intradermal injection in vivo compared to commercially available polymers. Furthermore, we observed enhanced uptake of pABOL-formulated saRNA in human skin explants and identified which cell phenotypes express the RNA. Finally, we found that hemagluttinin (HA)-encoding saRNA delivered by pABOL results in high HA-specific antibody titers and conferred complete protection against influenza challenge when administered intramuscularly. Due to the scalability of polymer synthesis and ease of formulation preparation, we anticipate that this polymer is highly clinically translatable as a delivery vehicle for saRNA for both vaccines and therapeutics.
