Work

Novel injectable polypeptide nanoparticle encapsulated siRNA targeting TGF‐β1 and COX‐2 for localized fat reduction I: Preclinical in vitro and animal models

Year: 2024

Type: article

Abstract: BACKGROUND: Obesity and localized fat accumulation continue to drive the demand for minimally invasive body contouring technologies including injectable compounds for local fat reduction. siRNA offers a potential for an injectable to specifically target and silence genes involved in adipogenesis with minimal inflammatory side effects. AIMS: This study evaluates the efficacy of STP705, an injectable containing siRNA encapsulated within histidine-lysine polypeptide (HKP) nanoparticles targeting transforming growth factor β1 (TGF-β1) and cyclooxygenase-2 (COX-2), crucial mediators in adipocyte differentiation and fat retention, using in vitro, porcine, and murine models. METHODS: In vitro experiments on mouse preadipocytes and in vivo trials using Diet Induced Obese (DIO) mice and Yucatan minipigs were conducted to assess the gene silencing efficiency, tissue localization, pharmacodynamics, and safety profile of STP705. RESULTS: STP705 effectively reduced the expression of TGF-β1 and COX-2, with a notable decrease in adipocyte volume and lipid content without adverse systemic effects. In DIO mice, the HKP-siRNA complex demonstrated precise localization to injected adipose tissue, maintaining significant gene silencing, and detectable levels of siRNA for up to 14 days post-administration. Similar results in minipigs showed a significant reduction in subcutaneous adipose tissue thickness. CONCLUSION: The results of these studies support the use of targeted siRNA therapy specifically targeting TGF-β1 and COX-2, for localized fat reduction, offering a potential minimally invasive alternative to current fat reduction methods.

Source: Journal of Cosmetic Dermatology

DOI: 10.1111/jocd.16535

Authors: Mark S. Nestor, John Hetzel, Nardin Awad, Vishnu Bhupalam, Patrick Lu, Michael Molyneaux

Institutions: University of Miami, Center for Clinical and Cosmetic Research, Sirnaomics (United States)

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,500