Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics

Area of Science:

• Molecular Biology
• Virology
• Biotechnology

Background:

• Rabies elimination requires effective post-exposure prophylaxis alongside mass dog vaccination.
• Aptamers and short-interfering RNAs (siRNAs) show therapeutic potential but are understudied for rabies.
• Rabies virus (RABV) remains a significant global health concern, necessitating novel treatment strategies.

Purpose of the Study:

• To develop and evaluate novel aptamers and siRNAs as post-exposure therapeutics against rabies virus (RABV).
• To investigate different delivery methods for siRNA, including Lipofectamine and aptamer conjugation.
• To assess the efficacy of these novel agents at various time points post-rabies virus infection.

Main Methods:

• Novel aptamer selection methods were employed.
• Short-interfering RNAs (siRNAs) were designed and synthesized.
• Delivery methods tested included Lipofectamine and aptamer-siRNA conjugates.
• Inhibition of RABV RNA and viral replication was quantified post-infection.

Main Results:

• One siRNA (N53) achieved an 80.13% reduction in viral RNA.
• Aptamer UPRET 2.03 showed a 61.3% reduction in viral RNA at 2 hours post-infection (p.i.).
• An aptamer-siRNA chimera (UPRET 2.03-N8) inhibited viral replication by 36.5% at 24 hours p.i.

Conclusions:

• This study presents the first evidence of significant RABV inhibition by aptamers.
• Lipofectamine RNAi-Max was validated as a delivery method for siRNA against RABV.
• Aptamers and siRNAs demonstrate potential as novel therapeutic options for rabies, possibly replacing rabies immunoglobulin (RIG).