DG9-conjugated morpholino rescues phenotype in SMA mice by reaching the CNS via a subcutaneous administration.

ABSTRACT: Antisense oligonucleotide-mediated (AO-mediated) therapy is a promising strategy to treat several neurological diseases, including spinal muscular atrophy (SMA). However, limited delivery to the CNS with AOs administered intravenously or subcutaneously is a major challenge. Here, we demonstrate a single subcutaneous administration of cell-penetrating peptide DG9 conjugated to an AO called phosphorodiamidate morpholino oligomer (PMO) reached the CNS and significantly prolonged the median survival compared with unconjugated PMO and R6G-PMO in a severe SMA mouse model. Treated mice exhibited substantially higher expression of full-length survival of motor neuron 2 in both the CNS and systemic tissues compared with nontreated and unmodified AO-treated mice. The treatment ameliorated the atroph

SUBMITTER: Aslesh T 

PROVIDER: S-EPMC10077475 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature