Making Sense of Antisense Gene Silencing; Tokyo Researchers Find Proteins That Bind to & Regulate Tocopherol-Conjugated Heteroduplex Oligonucleotides (Toc-HDOs) During Gene Silencing

Gene silencing therapies are used to interfere with, or "silence,” the expression of genes that are associated with disorders. Now, a team at TMDU has uncovered some of the cellular mechanisms by which the silencing therapies act in cells.

Antisense oligonucleotide (ASO) therapies use small strands of DNA or RNA that are antisense, or complementary, to the associated gene to interfere with its expression. ASO therapies are already available for some diseases, particularly neurological disorders, but their use is at a very early stage. It is known that modifying ASOs chemically can improve the efficacy of the therapy. The team at TMDU had previously achieved gene silencing by attaching alpha-tocopherol (Toc) to ASOs. They then created Toc-HDOs by attaching Toc to DNA/RNA heteroduplex oligonucleotides (HDOs), which are double-stranded molecules consisting of one strand of DNA and one strand of RNA. Toc-HDOs are more potent, more stable, and more efficiently taken up by target tissues than ASOs, and so have great therapeutic potential.

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