TY - JOUR
T1 - A Novel Piggyback Strategy for mRNA Delivery Exploiting Adenovirus Entry Biology
AU - Lee, Myungeun
AU - Rice-Boucher, Paul J.
AU - Collins, Logan Thrasher
AU - Wagner, Ernst
AU - Aulisa, Lorenzo
AU - Hughes, Jeffrey
AU - Curiel, David T.
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. Nonetheless, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied “piggyback” transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to actualize the promise of mRNA-based therapeutics.
AB - Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. Nonetheless, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied “piggyback” transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to actualize the promise of mRNA-based therapeutics.
KW - messenger Ribonucleic Acid (mRNA)
KW - streptavidin-polylysine (STAVpLys)
KW - targeted adenoviral vectors (Ad)
UR - http://www.scopus.com/inward/record.url?scp=85140631798&partnerID=8YFLogxK
U2 - 10.3390/v14102169
DO - 10.3390/v14102169
M3 - Article
C2 - 36298724
AN - SCOPUS:85140631798
SN - 1999-4915
VL - 14
JO - Viruses
JF - Viruses
IS - 10
M1 - 2169
ER -