Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles.

ABSTRACT: Recent advances in gapmer antisense oligonucleotides (ASOs) have led to the regulatory approval of ASO therapeutics that target the liver and central nervous system. Efficient delivery of gapmer ASOs to muscle tissue will further broaden their therapeutic applications. Here, we evaluated the knockdown activity of lipid-conjugated DNA/RNA heteroduplex oligonucleotides (HDOs) in muscle tissue. Cholesterol-conjugated HDO (Chol-HDO) exhibited effective gene suppression in both cardiac and skeletal muscles, outperforming unconjugated ASO and cholesterol-conjugated ASO (Chol-ASO). Chol-HDO and Chol-ASO showed greater binding to low-density lipoprotein (LDL); however, while Chol-ASO also exhibited enhanced binding to other serum proteins, Chol-HDO displayed weaker nonspecific interactions. Mechan

SUBMITTER: Matsuda-Kawabata S 

PROVIDER: S-EPMC12846741 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature