Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA

Schumann, Canan; Nguyen, Duc X.; Norgard, Mason; Bortnyak, Yulia; Korzun, Tetiana; Chan, Stephanie; Lorenz, Anna St.; Moses, Abraham S.; Albarqi, Hassan A.; Wong, Leon; Michaelis, Katherine; Zhu, Xinxia; Alani, Adam W. G.; Taratula, Olena R.; Krasnow, Stephanie; Marks, Daniel L.; Taratula, Oleh

doi:10.7150/thno.27847

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Theranostics 2018; 8(19):5276-5288. doi:10.7150/thno.27847 This issue Cite

Research Paper

Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA

Canan Schumann¹, Duc X. Nguyen¹, Mason Norgard², Yulia Bortnyak¹, Tetiana Korzun¹, Stephanie Chan¹, Anna St. Lorenz¹, Abraham S. Moses¹, Hassan A. Albarqi¹, Leon Wong¹, Katherine Michaelis², Xinxia Zhu², Adam W. G. Alani¹, Olena R. Taratula¹, Stephanie Krasnow¹, Daniel L. Marks^2✉, Oleh Taratula^1✉

1. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR 97201, USA
2. Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, Oregon 97239, USA

Citation:

Schumann C, Nguyen DX, Norgard M, Bortnyak Y, Korzun T, Chan S, Lorenz AS, Moses AS, Albarqi HA, Wong L, Michaelis K, Zhu X, Alani AWG, Taratula OR, Krasnow S, Marks DL, Taratula O. Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA. Theranostics 2018; 8(19):5276-5288. doi:10.7150/thno.27847. https://www.thno.org/v08p5276.htm

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Abstract

Muscle atrophy occurs during chronic diseases, resulting in diminished quality of life and compromised treatment outcomes. There is a high demand for therapeutics that increase muscle mass while abrogating the need for special dietary and exercise requirements. Therefore, we developed an efficient nanomedicine approach capable of increasing muscle mass.

Methods: The therapy is based on nanoparticle-mediated delivery of follistatin messenger RNA (mRNA) to the liver after subcutaneous administration. The delivered mRNA directs hepatic cellular machinery to produce follistatin, a glycoprotein that increases lean mass through inhibition of negative regulators of muscle mass (myostatin and activin A). These factors are elevated in numerous disease states, thereby providing a target for therapeutic intervention.

Results: Animal studies validated that mRNA-loaded nanoparticles enter systemic circulation following subcutaneous injection, accumulate and internalize in the liver, where the mRNA is translated into follistatin. Follistatin serum levels were elevated for 72 h post injection and efficiently reduced activin A and myostatin serum concentrations. After eight weeks of repeated injections, the lean mass of mice in the treatment group was ~10% higher when compared to that of the controls.

Conclusion: Based on the obtained results demonstrating an increased muscle mass as well as restricted fat accumulation, this nanoplatform might be a milestone in the development of mRNA technologies and the treatment of muscle wasting disorders.

Keywords: mRNA, polymeric nanoparticles, muscle atrophy, follistatin, activin A, myostatin

Citation styles

APA

Schumann, C., Nguyen, D.X., Norgard, M., Bortnyak, Y., Korzun, T., Chan, S., Lorenz, A.S., Moses, A.S., Albarqi, H.A., Wong, L., Michaelis, K., Zhu, X., Alani, A.W.G., Taratula, O.R., Krasnow, S., Marks, D.L., Taratula, O. (2018). Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA. Theranostics, 8(19), 5276-5288. https://doi.org/10.7150/thno.27847.

ACS

Schumann, C.; Nguyen, D.X.; Norgard, M.; Bortnyak, Y.; Korzun, T.; Chan, S.; Lorenz, A.S.; Moses, A.S.; Albarqi, H.A.; Wong, L.; Michaelis, K.; Zhu, X.; Alani, A.W.G.; Taratula, O.R.; Krasnow, S.; Marks, D.L.; Taratula, O. Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA. Theranostics 2018, 8 (19), 5276-5288. DOI: 10.7150/thno.27847.

NLM

CSE

Schumann C, Nguyen DX, Norgard M, Bortnyak Y, Korzun T, Chan S, Lorenz AS, Moses AS, Albarqi HA, Wong L, Michaelis K, Zhu X, Alani AWG, Taratula OR, Krasnow S, Marks DL, Taratula O. 2018. Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA. Theranostics. 8(19):5276-5288.

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