SMaRT^TM

Spliceosome-mediated RNA trans-splicing or SMaRT™ is VIRxSYS’s proprietary technology for reprogramming gene expression at the RNA level via trans-splicing reactions that occur during splicing of pre-messenger RNA.

RNA splicing is one of the most frequently occurring processes in biology and is an essential step in the flow of genetic information from DNA to protein synthesis. At any time, approximately 60,000 introns require splicing in a human cell nucleus. The average human gene encodes a primary transcript or pre-messenger RNA (pre-mRNA) containing seven introns. Splicing removes introns from the pre-mRNA to yield the mature mRNA and typically occurs within a single RNA molecule (cis-splicing).

SMaRT™ reprograms genes by trans-splicing between two different RNA molecules: a target cellular pre-mRNA and a pre-trans-splicing molecule or PTM. VIRxSYS’s PTMs are delivered by plasmid or viral vectors, which express the PTM as an RNA molecule. The PTM consists of a binding domain that directs the PTM to a specific sequence in the target pre-mRNA, a splicing domain and a coding domain, which contains the new or modified genetic information that is inserted or trans-spliced into the targeted pre-mRNA. The coding domain can be a single exon, multiple exons or an entire coding sequence. Utilizing SMaRT™, VIRxSYS has been able to achieve trans-splicing of up to 15% of endogenous target pre-mRNAs and 35% of targets introduced by transfection, although efficiencies as high as 50% and 75% have been observed in cell models of endogenous and transfected targets respectively.