RNA splicing is an attractive therapeutic modality for treating cancer and other diseases. In contrast to cis-splicing, where two exons from the same RNA transcript are joined, RNA trans-splicing is a cellular process whereby two exons on different pre- mRNA molecules are joined together through an RNA trans-splicing reaction to produce a chimeric RNA transcript.
Though RNA trans-splicing is a rare event in mammals, it can be triggered by delivery of an exogenous RNA molecule containing specialised sequences and regulatory domains.
Spliceor leverages RNA trans-splicing to selectively and precisely kill cells expressing tissue or disease-specific mRNAs. For example, the team has identified a specific class of RNA transcripts that are absent in normal cells but are highly expressed in liver and pancreatic cancer. Their therapeutic vector infects both healthy and transformed cells but trans-splicing only occurs in the tumour, leading to expression of the suicide gene Herpes simplex virus thymidine kinase (HSV-tk).
Once HSV-tk is activated by oral Ganciclovir, the cancer cells are selectively killed and the tumour self destructs.
Spliceor Therapeutics was spun out of the University of Cambridge by Start Codon and were joined by co-investors, Amadeus Capital Partners and Ajith Sukumaran.