Scavenger receptor-mediated uptake of antisense oligonucleotides into muscle cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06883
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: AOKI YOSHITSUGU 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 室長 (80534172)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: デュシェンヌ型筋ジストロフィー / アンチセンス核酸 / モルフォリノ / スカベンジャー受容体

Outline of Final Research Achievements

Duchenne muscular dystrophy (DMD) is an incurable, X-linked progressive muscle degenerative disorder that results from the absence of dystrophin protein.
Here, we study the uptake mechanism of phosphorodiamidate morpholino (PMO), which has been optimized to induce exon skipping in models of DMD. We show that the uptake of PMO is mediated by class A scavenger receptor subtypes (SCARAs) as demonstrated by competitive inhibition in vitro. Also, we newly developed SCARA1 and dystrophin double knockout mice to further confirm the uptake mechanism of PMO in vivo. These results suggest receptor-mediated uptake for PMO.

Free Research Field

分子生物学、筋病学