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.
Highlights
A global target for dog-mediated human rabies elimination has been set for the year2030 [1]
In the last few years, significant strides have been made with regard to rabies control and elimination through improved awareness and disease prioritization; the development and implementation of novel tools [2,54,55]; the formation of standardized, One Health, rabies-specific networks [56,57]; and a global strategic plan developed by the United
Despite recent improvements to recommendations for human rabies prophylaxis and treatment, there remain many challenges relating to ade
Summary
A global target for dog-mediated human rabies elimination has been set for the year. 2030 [1]. Organization (WHO) has—for the first time—included their recommendation for the use of certain mAb cocktails as a suitable alternative to RIG [12] and the first mAb has been licensed for use in India [5] Despite their success and their relative costeffectiveness compared to HRIG, there remain many tests and challenges associated with mAb cocktails that will need to be addressed before they become more widely available and accepted as a suitably cost-effective replacement for the current PEP regime [12]. This study sought to provide evidence towards the use of siRNAs and aptamers as suitable alternatives to RIG, or as a possible treatment for RABV after the onset of symptoms, through in vitro trials. Aptamer–siRNA chimera molecules were created to determine whether the combined actions of these two molecules would be greater than the individual components
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