Emerging siRNA Platform Offers New Metabolic Disorder Therapies

A new round of seed financing announced on Dec. 3, 2025 by biotechnology company Junevity aims to move the company’s cell reprogramming with silencing RNA (also known as short interfering or small interfering RNA) (siRNA) platform, an emerging approach to metabolic disease treatment, toward human testing. The company expanded its seed funding to $20 million following a newly added $10 million investment led by Goldcrest Capital and Godfrey Capital. Junevity plans to use the capital to advance its lead candidate, JUN_01, toward investigational new drug–enabling work and initial clinical studies for type 2 diabetes and obesity (1).

According to a company press release, Junevity’s scientific founders were the first to show that repressing a single transcription factor could revert human cells to a healthier state, laying the groundwork for the company’s technology platform (1,2). The progression of this research into drug development may have broader implications for how industry approaches metabolic disorders, particularly as the field seeks more durable and better-tolerated options (3).

“JUN_01 offers a unique and promising combination of improved insulin sensitivity and weight loss, with dosing every six months,” said John Bamforth, PhD, the former chief marketing officer at Eli Lilly and Company and advisor to Junevity, in the release (1). “This profile could fill an important need for effective and tolerable long-term diabetes and weight management either alone or in combination with GLP-1s [glucagon-like peptide-1].”

What makes siRNA reprogramming a different metabolic intervention?

Preclinical data suggest that JUN_01 may act by reprogramming metabolic tissues to a healthier state, according to the company. Studies showed reduced blood glucose, improved insulin sensitivity, weight loss, and lean-mass preservation, alongside infrequent dosing and safety attributes associated with siRNA modalities, Junevity stated in the release (1).

The therapeutic concept is built on identifying and suppressing transcription factors that drive chronic metabolic dysfunction, the company explained (1). For instance, JUN_01 targets a regulator implicated in insulin signaling and appetite, which is selected through Junevity’s discovery platform (RESET) (4). The platform integrates human disease data, genetic linkages, and computational analyses.

Early data from JUN_01 studies also indicate potential resistance to weight regain once treatment stops—weight gain post-treatment being an issue that continues to challenge current metabolic interventions (5). If these effects translate into clinical settings, then this approach may introduce a new direction for metabolic therapies and influence how combination regimens with incretin-based drugs are structured, the company noted (1). First-in-human trials are anticipated to start in the second half of 2026.

Could cell reprogramming expand therapeutic scope beyond metabolism?

The company’s platform stems from research conducted at the University of California, San Francisco, where co-founder Janine Sengstack developed methods to use omics, genetic data, and machine-learning tools to identify new transcription factor targets. These targets have traditionally been difficult to drug, and the ability to reach them with siRNA could widen the landscape of therapeutic discovery (1).

“JUN_01 is a next-generation siRNA candidate for type 2 diabetes and obesity and the first cell reprogramming candidate with siRNA for metabolism,” said John Hoekman, co-founder and CEO of Junevity, in the release (1). “By reprogramming metabolic tissue to a healthy state, we see profound and durable benefits beyond today’s standard of care. We look forward to bringing this to patients in our initial clinical studies.”

The company is also expanding research into neurodegeneration and other areas involving complex tissue dysfunction. The broader significance of this research lies in whether siRNA-driven transcription factor modulation can become a translatable therapeutic model for conditions historically limited by target accessibility (6).

References

1. Junevity. Junevity Expands Seed Funding to $20 Million for Cell Reprogramming with siRNA. Press Release. Dec. 3, 2025.
2. Mariani, J. N.; Mansky, B.; Madsen, P.M.; et al. Repression of Developmental Transcription Factor Networks Triggers Aging-Associated Gene Expression in Human Glial Progenitor Cells. Nat. Commun. 2024, 15, 3873. DOI: 10.1038/s41467-024-48118-2
3. Zhang, Y.; Chen, H.; Hong, L.; et al. Inclisiran: A New Generation of Lipid-Lowering siRNA Therapeutic. Front. Pharmacol. 2023, 14, 1260921. DOI: 10.3389/fphar.2023.1260921
4. Junevity. RESET Platform. junevity.com (accessed Dec. 3, 2025).
5. Rodriguez, P. J.; Zhang, V.; Gratzl, S.; et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults with Overweight or Obesity. JAMA Netw Open. 2025, 8 (1), e2457349. DOI: 10.1001/jamanetworkopen.2024.57349
6. Kumar, S.; Liu, G. S. Recent Advances in RNA-Targeting Therapy for Neurological Diseases. Neural Regener. Res. 2023, 18 (12), 2663–2664. DOI: 10.4103/1673-5374.373658