Journal article

Endosomal escape cell-penetrating peptides significantly enhance pharmacological effectiveness and CNS activity of systemically administered antisense oligonucleotides.

Mohadeseh Dastpeyman, Ramin Sharifi, Azin Amin, John A Karas, Brittany Cuic, Yijun Pan, Joseph A Nicolazzo, Bradley J Turner, Fazel Shabanpoor

International Journal of Pharmaceutics | Elsevier BV | Published : 2021


Antisense oligonucleotides (ASOs) are an emerging class of gene-specific therapeutics for diseases associated with the central nervous system (CNS). However, ASO delivery across the blood-brain barrier (BBB) to their CNS target cells remains a major challenge. Since ASOs are mainly taken up into the brain capillary endothelial cells interface through endosomal routes, entrapment in the endosomal compartment is a major obstacle for efficient CNS delivery of ASOs. Therefore, we evaluated the effectiveness of a panel of cell-penetrating peptides (CPPs) bearing several endosomal escape domains for the intracellular delivery, endosomal release and antisense activity of FDA-approved Spinraza (Nusi..

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University of Melbourne Researchers