What is Spliceosome-mediated RNA therapy?

Spliceosome-mediated RNA trans-splicing or SMaRTTM represents a completely new approach to gene medicine and is defined as RNA therapy since the correction/change occurs at the pre-mRNA level.

SMaRT™ RNA therapy uses gene therapy vectors to deliver VIRxSYS’s proprietary pre-trans-splicing molecules (PTMs). PTMs that encode correct genetic sequences have been used to repair mutant mRNAs from genes associated with human disease. Because the coding sequence can consist of one or more exons, a single PTM can be used to correct all the mutations in the region of the target RNA that is being replaced. Alternatively, these PTMs can encode toxins that can be used to kill diseased cells (e.g. cancer cells).

RNA Therapy Programs: VIRxSYS’s RNA therapy for the blood coagulation disorder Hemophilia A (Factor VIII deficiency) is in pre-clinical development. VIRxSYS has a second discovery program to increase high density lipoprotein (HDL). In the past, Intronn demonstrated proof of principle in 12 different disease models resulting in more than 30 publications in scientific journals.

Advantages: SMaRT™ RNA therapy offers several significant advantages over traditional gene therapy approaches:

o VIRxSYS’s PTMs take advantage of the natural regulation of the target pre-mRNA. Trans-splicing occurs only where and when the target pre-mRNA is expressed and thus avoids issues of ectopic expression observed in conventional gene therapy. In addition, SMaRT™ confers endogenous regulation to transgene expression because the level of RNA repair correlates with the level of the cellular target pre-mRNA.

o PTMs can be significantly smaller than the transgenes used in conventional gene therapy, because PTMs carry only a portion of the full length CDNA. Since many delivery systems are limited by the size of the genetic material they transfer, the smaller size of PTMs allow the use of a wider range of vectors to treat diseases not amenable to conventional gene therapy approaches.