Version 1
: Received: 6 May 2024 / Approved: 6 May 2024 / Online: 6 May 2024 (09:54:35 CEST)
How to cite:
Leckie, J.; Yokota, T. Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA. Preprints2024, 2024050274. https://doi.org/10.20944/preprints202405.0274.v1
Leckie, J.; Yokota, T. Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA. Preprints 2024, 2024050274. https://doi.org/10.20944/preprints202405.0274.v1
Leckie, J.; Yokota, T. Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA. Preprints2024, 2024050274. https://doi.org/10.20944/preprints202405.0274.v1
APA Style
Leckie, J., & Yokota, T. (2024). Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA. Preprints. https://doi.org/10.20944/preprints202405.0274.v1
Chicago/Turabian Style
Leckie, J. and Toshifumi Yokota. 2024 "Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA" Preprints. https://doi.org/10.20944/preprints202405.0274.v1
Abstract
Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
