Date: Tuesday 20th May
Time: 12.30 – 13.30
Title: Watch your step: antisense oligonucleotides acting outside of genes
Speaker: Dr Pawel Grzechnik, University of Manchester
Abstract:
Antisense oligonucleotides (ASOs) are short, chemically modified oligonucleotides that bind to RNA in a target-specific manner to modulate gene expression. These versatile molecules can be tailored to groups of patients or individual cases to specifically target and alter defective mRNAs, thereby slowing or halting the progression of genetic diseases. Although ASOs are rapidly emerging class of therapeutic agents, with several approved drugs available on the market, their molecular mechanism of action and implications for the genome are still not fully understood.
We have discovered a novel mechanism of ASO-dependent gene regulation. We found that ASOs can act downstream of the coding sequences to decrease the levels of the mRNA transcribed upstream of the binding site. Such ASOs, located outside of the genes, disturb correct mRNA 3’ end formation and lead to transcript degradation. Our data shed light on how ASOs affect molecular mechanisms regulating mRNA synthesis, provide new options for ASO-dependent downregulation of gene expression, and highlight additional conditions to consider or the design and evaluation of therapeutic ASOs.
Location: St Mary’s Hospital, Oxford Road, Manchester.