O017 - DEVELOPMENT OF LIPID NANOPARTICLE-MEDIATED DELIVERY OF LARGE TYPE AMINO ACID TRANSPORTER 1 (LAT1) MRNA TO PRESERVE SKELETAL MUSCLE MASS IN A HINDLIMB IMMOBILIZATION MOUSE MODEL OF MUSCLE ATROPHY.

O017

DEVELOPMENT OF LIPID NANOPARTICLE-MEDIATED DELIVERY OF LARGE TYPE AMINO ACID TRANSPORTER 1 (LAT1) MRNA TO PRESERVE SKELETAL MUSCLE MASS IN A HINDLIMB IMMOBILIZATION MOUSE MODEL OF MUSCLE ATROPHY.

W. Alabdullatif^1,*, I. A. Bindayel¹, M. M. Abdulmeaty¹

¹Community Health Sciences , King Saud University , Riyadh, Saudi Arabia

Rationale: This study aimed to evaluate the effects of in vitro transcribed (IVT) LAT1 mRNA lipid nanoparticle (LNP) delivery to enhance LAT1 expression and leucine uptake in a hindlimb immobilization mouse model of muscle atrophy.

Methods: Twenty male Swiss albino mice (6–8 weeks old, 25–30 g) were randomly assigned to four groups (n=5). Three groups underwent hindlimb immobilization, while one group served as a healthy control. Group 1: Intramuscular injection of 5 µg LAT1 mRNA LNPs; Group 2: 10 µg LAT1 mRNA LNPs; Group 3: Immobilized saline control; Group 4: Healthy saline control. At the end of the study, mice received oral leucine (0.8 g/kg). Two hours later, animals were euthanized, and samples were collected. 

Results: LAT1 protein expression was increased in both treated and immobilized saline groups compared to healthy controls. Activation of the mTOR signaling pathway and increased S6K1 expression were also observed in all immobilized groups. Muscle BCAA concentrations were significantly higher in all immobilized groups compared to healthy controls (p < 0.01). LAT1 mRNA LNP-treated mice showed improved muscle morphology, with increased fiber diameter and reduced inflammatory markers, particularly in the 10 µg group. Immunohistochemistry revealed weak LAT1 expression in healthy muscle, strong diffuse expression in immobilized saline-treated muscle, and more localized, regulated LAT1 expression in LAT1 treated groups.

Conclusion: This study showed that IVT mRNA therapy of LAT1 mRNA LNPs improved muscle structural integrity and modulates LAT1 expression in an immobilization-induced muscle atrophy model. These findings suggest a potential therapeutic role for IVT LAT1 mRNA delivery in preserving muscle function for the prevention and treatment of muscle atrophy.

Disclosure of Interest: None declared