Cell-penetrating peptide-conjugated Morpholino rescues SMA in a symptomatic preclinical model.

ABSTRACT: Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality. Recently approved SMA therapies have transformed a deadly disease into a survivable one, but these compounds show a wide spectrum of clinical response and effective rescue only in the early stages of the disease. Therefore, safe, symptomatic-suitable, non-invasive treatments with high clinical impact across different phenotypes are urgently needed. We conjugated antisense oligonucleotides with Morpholino (MO) chemistry, which increase SMN protein levels, to cell-penetrating peptides (CPPs) for better cellular distribution. Systemically administered MOs linked to r6 and (RXRRBR)₂XB peptides crossed the blood-brain barrier and increased SMN protein levels remarkably, causing

SUBMITTER: Bersani M 

PROVIDER: S-EPMC8899506 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature