A novel viral vaccine platform based on engineered transfer RNA

Area of Science:

• Virology
• Molecular Biology
• Vaccine Development

Background:

• Emerging viral outbreaks necessitate rapid vaccine development.
• Controlling virus replication via premature termination codons (PTCs) is a promising strategy for live, replication-defective vaccines.

Purpose of the Study:

• To investigate anticodon-engineered transfer RNAs (ACE-tRNAs) as precision switches for controlling PTC-containing viruses.
• To evaluate ACE-tRNAs as a novel platform for rapid viral vaccine development.

Main Methods:

• Engineered transfer RNAs (ACE-tRNAs) to control premature termination codon (PTC) read-through in viruses.
• Utilized HIV-1 pseudotyped virus (RNA virus model) and Pseudorabies virus (PRV, DNA virus model).
• Assessed ACE-tRNA efficacy in controlling viral replication and in vivo immunogenicity.

Main Results:

• ACE-tRNAs demonstrated higher potency in reading through PTCs compared to genetic code expansion (GCE) technology.
• ACE-tRNAs precisely controlled the production and replication of PTC-containing viruses (HIV-1 and PRV).
• PTC-engineered PRV was fully attenuated in mice, and immunization provided complete protection against wild-type challenge.

Conclusions:

• Replication-controllable PTC-containing viruses based on ACE-tRNAs offer a new strategy for rapid virus attenuation.
• This ACE-tRNA technology serves as a platform for the swift development of effective viral vaccines.