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ARTICLE | Translation in Brief

Heteroduplicity's lure

RNA bound to α-tocopherol boosts antisense DNA delivery and gene silencing

October 8, 2015 7:00 AM UTC

A collaboration between researchers from Tokyo Medical and Dental University and Isis Pharmaceuticals Inc. (NASDAQ: ISIS) has produced a method to enhance the therapeutic index of antisense oligonucleotides by converting the single-stranded molecules into double-stranded DNA/RNA hybrid heteroduplexes. The added RNA provides a handle for conjugating chemicals that enable uptake of the molecules by target organs without interfering with the antisense activity.

In a study published in Nature Communications, the researchers showed hybrids of DNA antisense oligos and complementary RNAs conjugated to the vitamin E molecule α-tocopherol - dubbed Toc-HDOs - reduced target gene expression at lower doses than the DNA oligonucleotides alone. (See Distillery, page 22)...