How AAV vectors and a newly identified hormone connected basic mechanism to translational relevance in metabolic and neural regulation.
AAV vectors for basic research have become a versatile tool to uncover gene regulation and metabolic activity through gene knockdown or overexpression (Haggerty et al. 2019). In a recent interview in Cell & Gene Therapy Insights, Exploring asprosin: how AAV vectors are advancing hormone research,” Bijoya Basu from Case Western Reserve University School of Medicine described a case study using AAV vector technology to investigate hormone biology and translational science.
In 2016, researchers studying a rare genetic condition known as neonatal progeroid syndrome (NPS) made an unexpected discovery: a new hormone called asprosin (Romere et al. 2016). Asprosin circulates in the bloodstream and influences glucose metabolism, appetite, and thirst regulation (Romere et al. 2016, Mishra et al. 2024).
AAV vectors for basic research have become a versatile tool to uncover gene regulation and metabolic activity through gene knockdown or overexpression (Haggerty et al. 2019).
Uncovering asprosin functionality
Since its discovery, asprosin has evolved from a metabolic curiosity to recognizing it as an important signal in human physiology. Early studies revealed that it stimulates hepatic glucose release during fasting, but newer work has uncovered broader effects on central nervous system function. Circulating through the bloodstream, asprosin plays a central role in controlling glucose balance, appetite, and thirst (Duerrschmid et al. 2017, Romere et al. 2016, Mishra et al. 2024).
Yet determining how asprosin works has not been straightforward. Like many recombinant proteins, in vitro produced asprosin can vary from batch to batch, leading to inconsistent results. Researchers at Case Western Reserve University, led by Dr. Atul Chopra and MD-PhD candidate Bijoya Basu, encountered these challenges firsthand. To overcome this, the team turned to adeno-associated virus (AAV) vectors as a tool for controlled hormone expression in vivo.
AAV as a trustworthy platform for overexpression
In animal models, AAV vectors allowed for the sustained, stable expression of asprosin. AAV provides low immunogenicity and consistent, long-term expression. This contrasts to using adenoviral systems that can induce immunological responses and cause disease.
Using AAV to elevate circulating asprosin approximately twofold (the same increase observed in obese patients) allowed the team to model the hormone’s physiological effects under realistic conditions (Mishra et al. 2021). The mice showed higher glucose levels, increased body weight, and greater water intake, all of which could be reversed by neutralizing asprosin with monoclonal antibodies. Both the AAV strategy and the hormone’s function in metabolic regulation were confirmed by these reversible reactions.
Overcoming recombinant protein challenges
Conventional recombinant protein studies require repeated dosing to maintain physiological hormone levels, often leading to inconsistent exposure and rapid clearance. In contrast, AAV allows sustained hormone expression and provides a more realistic model of chronic conditions.
AAV-driven asprosin expression also helped optimize ELISA assays for more accurate measurement of circulating hormone levels (Mishra & Chopra, 2022), improving both biological insight and assay reproducibility. For labs working on newly discovered hormones or unstable peptides, this kind of steady in vivo expression can be the difference between noisy data and clear biology.
Using AAV vectors for basic research
The success of AAV in studying asprosin illustrates how viral vector platforms can support basic endocrine and metabolic research, and not just late-stage therapeutics. For newly discovered hormones or proteins that are difficult to synthesize or are unstable as recombinant proteins, AAV offers a reliable, physiologically relevant expression system without requiring gene editing.
Basu points out that research approaches for hormonal pathways are changing because of AAV’s stability, safety, and long-term delivery. By bridging the gap between conventional biochemistry and modern vector-based translational research, AAV gene therapy tools are driving biological insights.
AAV vectors for basic research: How AAV vectors and a newly identified hormone connected basic mechanism to translational relevance in metabolic and neural regulation.
Summary – Using AAV vectors for basic research
The same AAV technologies driving clinical gene therapies can also accelerate fundamental biological discovery at the bench, helping researchers connect hormones, circuits, and behavior with more control and less variability.
Interested in applying AAV vectors for basic research in your own hormone or metabolic studies? Contact Vector Biolabs to discuss vector design, serotype selection, and production options for your next experiment.
References – AAV vectors for basic research
Haggerty DL, Grecco GG, Reeves KC, Atwood B. Adeno-Associated Viral Vectors in Neuroscience Research. Mol Ther Methods Clin Dev. 2019 Nov 26;17:69-82.
Cell & Gene Therapy Insights 2025; 11(6), 651–656 · DOI: 10.18609/cgti.2025.075
Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR. Asprosin, a Fasting-Induced Glucogenic Protein Hormone. Cell. 2016 Apr 21;165(3):566-79.
Duerrschmid C, He Y, Wang C, Li C, Bournat JC, Romere C, Saha PK, Lee ME, Phillips KJ, Jain M, Jia P, Zhao Z, Farias M, Wu Q, Milewicz DM, Sutton VR, Moore DD, Butte NF, Krashes MJ, Xu Y, Chopra AR. Asprosin is a centrally acting orexigenic hormone. Nat Med. 2017 Dec;23(12):1444-1453. https://pmc.ncbi.nlm.nih.gov/articles/PMC5720914/pdf/nihms910781.pdf
Mishra I, Feng B, Basu B, Brown AM, Kim LH, Lin T, Raza MA, Moore A, Hahn A, Bailey S, Sharp A, Bournat JC, Poulton C, Kim B, Langsner A, Sathyanesan A, Sillitoe RV, He Y, Chopra AR. The cerebellum modulates thirst. Nat Neurosci. 2024 Sep;27(9):1745-1757.
Mishra I, Duerrschmid C, Ku Z, He Y, Xie W, Silva ES, Hoffman J, Xin W, Zhang N, Xu Y, An Z, Chopra AR. Asprosin-neutralizing antibodies as a treatment for metabolic syndrome. Elife. 2021 Apr 27;10: e63784.
Mishra I, Chopra AR. Overexpression and ELISA-based detection of asprosin in cultured cells and mice. STAR Protoc. 2022 Dec 16;3(4):101762.