Systemic DNA/RNA heteroduplex oligonucleotide administration for regulating the gene expression of dorsal root ganglion and sciatic nerve.
DNA/RNA heteroduplex
MT: Oligonucleotides: Therapies and Applications
antisense oligonucleotide
dorsal root ganglion
neuropathic pain
peripheral nerve disease
sciatic nerve
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
14 Jun 2022
14 Jun 2022
Historique:
received:
23
08
2021
accepted:
03
05
2022
entrez:
13
6
2022
pubmed:
14
6
2022
medline:
14
6
2022
Statut:
epublish
Résumé
Neuropathic pain, a heterogeneous condition, affects 7%-10% of the general population. To date, efficacious and safe therapeutic approaches remain limited. Antisense oligonucleotide (ASO) therapy has opened the door to treat spinal muscular atrophy, with many ongoing clinical studies determining its therapeutic utility. ASO therapy for neuropathic pain and peripheral nerve disease requires efficient gene delivery and knockdown in both the dorsal root ganglion (DRG) and sciatic nerve, key tissues for pain signaling. We previously developed a new DNA/RNA heteroduplex oligonucleotide (HDO) technology that achieves highly efficient gene knockdown in the liver. Here, we demonstrated that intravenous injection of HDO, comprising an ASO and its complementary RNA conjugated to α-tocopherol, silences endogenous gene expression more than 2-fold in the DRG, and sciatic nerve with higher potency, efficacy, and broader distribution than ASO alone. Of note, we observed drastic target suppression in all sizes of neuronal DRG populations by
Identifiants
pubmed: 35694210
doi: 10.1016/j.omtn.2022.05.006
pii: S2162-2531(22)00119-6
pmc: PMC9167871
doi:
Types de publication
Journal Article
Langues
eng
Pagination
910-919Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
T.Y. collaborates with Takeda Pharmaceutical and serves as an academic advisor to Rena Therapeutics and Nissan Chemical Corporation. The other authors declare no competing interests.
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