Antisense oligonucleotides (ASOs) are promising gene-targeting therapies, but endosomal escape and nuclear localization limit their effectiveness. Only 1-2% of ASOs reach their target mRNA. Strategies like lipid nanoparticles, pH-responsive materials, and membrane-destabilizing agents aim to improve ASO delivery. Enhancing nuclear localization is also critical for splice-switching oligonucleotides (SSOs). Overcoming these barriers is essential for making ASO-based therapies viable in clinical settings.

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