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

Larissa Goli; Jessica Stoodley; Suzan M Hammond; Richard Raz

doi:10.1007/978-1-0716-1752-6_31

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

Methods Mol Biol. 2022:2383:491-513. doi: 10.1007/978-1-0716-1752-6_31.

Authors

Larissa Goli^#^{1

2}, Jessica Stoodley^#¹, Suzan M Hammond¹, Richard Raz³

Affiliations

¹ Department of Paediatrics, University of Oxford, Oxford, UK.
² Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
³ Department of Paediatrics, University of Oxford, Oxford, UK. [email protected].

^# Contributed equally.

PMID: 34766309
DOI: 10.1007/978-1-0716-1752-6_31

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.

Keywords: Antisense oligonucleotides; Cell-penetrating peptide; In vivo pup administrations; Peptide oligonucleotide conjugates; Spinal muscular atrophy; Survival motor neuron; Taiwanese SMA mouse model.

MeSH terms

Animals
Cell-Penetrating Peptides
Disease Models, Animal
Mice
Muscular Atrophy, Spinal* / drug therapy
Oligonucleotides
Oligonucleotides, Antisense

Substances

Cell-Penetrating Peptides
Oligonucleotides
Oligonucleotides, Antisense