Abstract:
If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective
mass dog vaccination needs to be complemented by effective prophylaxis for individuals exposed
to rabies. Aptamers and short-interfering RNAs (siRNAs) have been successful in therapeutics,
but few studies have investigated their potential as rabies therapeutics. In this study, siRNAs and
aptamers—using a novel selection method—were developed and tested against rabies virus (RABV)
in a post-infection (p.i.) scenario. Multiple means of delivery were tested for siRNAs, including
the use of Lipofectamine and conjugation with the developed aptamers. One siRNA (N53) resulted
in an 80.13% reduction in viral RNA, while aptamer UPRET 2.03 demonstrated a 61.3% reduction
when used alone at 2 h p.i. At 24 h p.i., chimera UPRET 2.03-N8 (aptamer-siRNA) resulted in a 36.5%
inhibition of viral replication. To our knowledge, this is the first study using siRNAs or aptamers
that (1) demonstrated significant inhibition of RABV using an aptamer, (2) tested Lipofectamine
RNAi-Max as a means for delivery, and (3) produced significant RABV inhibition at 24 h p.i. This
study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin
(RIG) replacements or therapeutic options for RABV and provides strong evidence towards their
further investigation.
