A team of researchers led by Rutgers' Samuel Gunderson has developed a novel gene silencing platform with very significant improvements over existing RNAi approaches.
This may enable the development and discovery of a new class of drugs to treat a wide array of diseases. Critical to the technology is the approach this team took to specifically target RNA biosynthesis.
The research findings are reported in the journal Nature Biotechnology , published online in the February 15th issue.
Gunderson, an associate professor in the Department of Molecular Biology and Biochemistry at Rutgers, The State University of New Jersey, has created highly efficient gene silencing agents that function via a novel mechanism of action. The agents are single-stranded oligonucleotides, called U1 Adaptors, that have dual, and independent, functions. First is a target-gene binding domain that can be tailored to any gene. The second domain inhibits mRNA maturation by binding U1 snRNP, a component of the cellular splicing apparatus.
By combining both capabilities in the same molecule, the U1 Adaptor can inhibit the pre-mRNA maturation step of polyA tail addition in a gene specific manner. Further, the domains of the oligonucleotide are independent so transcript binding and U1 snRNP binding can be independently optimized and adapted to a wide array of genes associated with disease.