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ABSTRACT We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for

treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate markers using the adenovirus delivery method. Rate

of weight loss and percentage satiety were significantly greater in the mice treated with Ad-leptin. These findings were associated with lower peak serum leptin levels with Ad-leptin (22.9 ±

 2.6 ng/ml for the human gene, and 48.9 ± 11.5 ng/ml for the murine gene) compared to rh-leptin (385.2 ± 36.0 ng/ml). (Values are given as mean ± standard error of the mean.) Importantly,

rh-leptin and ex vivo-expressed Ad-leptin were equivalently active in a functional cell-based assay. The primary difference in the two therapeutic approaches is the continuous chronic

secretion of leptin mediated by gene delivery, versus the intermittent bolus delivery and rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo findings suggest that

leptin effects are better achieved at lower steady-state levels, a pharmacological feature attained here by gene therapy. These findings may have implications for the potential use of leptin

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FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS LEPTIN ALTERS ENERGY INTAKE AND FAT MASS BUT NOT ENERGY EXPENDITURE IN LEAN SUBJECTS Article Open access 13 October

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THERAPIES VECTORS FOR BALANCING EFFICACY, LONGEVITY AND SAFETY FOR CLINICAL APPLICATION Article 26 March 2025 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Human Genetics,

Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA MA Morsy, MC Gu, JZ Zhao & CT Caskey * Biometrics Research, Merck and Co, Inc, WP26A-3000, Sumneytown Pike,

West Point, 19486, PA, USA DJ Holder * Laboratory Animal Resources, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA IT Rogers, WJ Pouch & SL Motzel * Research

Resources Administration, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA HJ Klein * Cellular and Molecular Biology, Merck and Co, Inc, WP26A-3000, Sumneytown

Pike, West Point, 19486, PA, USA SK Gupta & X Liang * Genetics and Molecular Biology, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA MR Tota & CI

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Morsy, M., Gu, M., Zhao, J. _et al._ Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse. _Gene

Ther_ 5, 8–18 (1998). https://doi.org/10.1038/sj.gt.3300565 Download citation * Received: 01 July 1997 * Accepted: 08 September 1997 * Published: 04 March 1998 * Issue Date: 01 January 1998

* DOI: https://doi.org/10.1038/sj.gt.3300565 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * adenovirus * recombinant leptin * obesity * diabetes *

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