Evaluating Efficacy of Peptide-Delivered Oligonucleotides Using the Severe Taiwanese SMA Mouse Model.

Abstract

Oligonucleotides (ONs) are therapeutic macromolecules with great potential for the treatment of neurological conditions, including spinal muscular atrophy (SMA), a neurodegenerative disease. However, the neurovascular unit severely limits their distribution to the neural parenchyma of the brain and the spinal cord. Cell-penetrating peptides (CPPs) can be conjugated to oligonucleotides to increase their delivery across biological barriers. In this chapter, we describe the synthesis and conjugation of CPPs to oligonucleotides, and the use of a severe SMA mouse model to test in vivo the efficacy of CPP-delivered oligonucleotides, using ELISA, western blot, and TaqMan™ RT-qPCR assays.

• Authors: Larissa Goli, Jessica Stoodley, Suzan M Hammond, Richard Raz
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 2383 Pg. 491-513 ( 2022) ISSN: 1940-6029 [Electronic] United States
• PMID: 34766309 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Cell-Penetrating Peptides
• Oligonucleotides
• Oligonucleotides, Antisense

Topics

• Animals
• Cell-Penetrating Peptides
• Disease Models, Animal
• Mice
• Muscular Atrophy, Spinal (drug therapy)
• Oligonucleotides
• Oligonucleotides, Antisense