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American Heart Association

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Final ID: 4129675

Effective Transcatheter Intracoronary Delivery of mRNA-Lipid Nanoparticle Targeting on The Heart

Abstract Body (Do not enter title and authors here):
Introduction
mRNA has great potential to provide new medical innovations in the treatment of heart failure. Lipid nanoparticles (LNPs) are an established and effective mRNA delivery system. However, effectively delivering LNPs to the heart remains a significant challenge. We evaluated the efficacy of transcatheter intracoronary (IC) administration compared to intravenous (IV) and intramyocardial (IM) administration as methods for delivering.

Methods
Normal rabbits were used to examine each route of administration. Fluorescence (ATTO 700)-labeled LNP encapsulating Firefly Luciferase (FLuc) mRNA (25 ug/kg) were used to confirm the in vivo mRNA-LNP dynamics. The LNP accumulation and FLuc expression were verified using an in vivo imaging system (IVIS) 4 hours post-administration, followed by immunohistochemical analysis. The same experiments were conducted in an ischemia-reperfusion (I/R) model.

Results
In the normal model, IVIS spectrum data showed that LNPs accumulated in the order of IM, IC and IV groups, with FLuc expression significantly higher in the IC group than in the IV group and comparable to the IM group (A). Histological analysis revealed that FLuc-expressing cells were mainly found in troponin T-positive cardiomyocytes at the injection site in the IM group and throughout the heart in the IC group (B). In the I/R model, LNP accumulation and FLuc expression were increased in the IV group compared to the normal model, whereas, in the IC and IM groups LNP accumulation and FLuc expression levels were similar to those in the normal model (C). Histological analysis revealed more FLuc-expressing cells in the infarcted area in all groups, but higher FLuc expression was observed in remote areas in the IC group (D).

Conclusions
IC administration effectively delivered mRNA-LNPs not only to the damaged area but also to the remote area (non-damaged area) in the diseased heart, suggesting a safe and useful method for delivery to a wider range of cardiomyocytes in the heart.
  • Handa, Kazuma  ( Osaka University , Osaka , Japan )
  • Fujishiro, Anri  ( Terumo Corporation, Innovation Center , Kanagawa , Japan )
  • Hirano, Kunio  ( Terumo Corporation, Innovation Center , Kanagawa , Japan )
  • Miyagawa, Shigeru  ( Osaka university graduate school , Suita Osaka , Japan )
  • Kawamura, Masashi  ( Osaka University , Osaka , Japan )
  • Sasai, Masao  ( OSAKA UNIVERSITY , Osaka , Japan )
  • Matsuzaki, Takashi  ( Osaka University , Osaka , Japan )
  • Harada, Akima  ( Osaka University , Osaka , Japan )
  • Miki, Kenji  ( Osaka Univerisy , Suita, Osaka , Japan )
  • Fujimura, Lisa  ( Osaka University , Osaka , Japan )
  • Saito, Shunsuke  ( Osaka University Graduate School of Medicine , Suita, Osaka , Japan )
  • Tsuneda, Ryo  ( Terumo Corporation, Innovation Center , Kanagawa , Japan )
  • Author Disclosures:
    Kazuma Handa: DO NOT have relevant financial relationships | Anri Fujishiro: No Answer | Kunio Hirano: DO have relevant financial relationships ; Employee:Terumo Corporation (Japan):Active (exists now) | Shigeru Miyagawa: No Answer | Masashi Kawamura: DO NOT have relevant financial relationships | Masao Sasai: DO have relevant financial relationships ; Advisor:Cuorips. Inc.:Active (exists now) | Takashi Matsuzaki: No Answer | Akima Harada: DO NOT have relevant financial relationships | Kenji Miki: DO NOT have relevant financial relationships | Lisa Fujimura: No Answer | Shunsuke Saito: DO NOT have relevant financial relationships | Ryo Tsuneda: No Answer
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Advanced Methodologies to Decipher Heart Failure Pathophysiology

Monday, 11/18/2024 , 08:00AM - 09:15AM

Abstract Oral Session

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