Evidence mapPaperPMID 42321077Full record

ArticleTrends in biotechnology2026

Engineering single-dose plasmid DNA for sustained in vivo delivery of designer incretins.

Ebony N Gary, Yangcheng Gao, Casey E Hojecki, Nicholas J Tursi, Wujuan Zhang, Aaron R Goldman, Niklas Laenger, Martina Tomirotti, Mohammad Suhail Khan, Riya Sahai and 9 more

Abstract read
In one paragraph

Article in Trends in biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Ebony N GaryVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: egary@wistar.org.
Yangcheng GaoVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Casey E HojeckiVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Nicholas J TursiVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Wujuan ZhangVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Aaron R GoldmanVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Niklas LaengerVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Biology Department, Saint Joseph's University, Philadelphia, PA 19104, USA.
Martina TomirottiVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Mohammad Suhail KhanVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Riya SahaiVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jacob OblanderVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Department of Biology, Rutgers University-Camden, Camden, NJ 08102, USA.
Jinwei HuangVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Zi Jie LinVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Jiayan CuiVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Xiaoyang LiuVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Laurent HumeauInovio Pharmaceuticals, Bluebell, PA 19462, USA.
Jesper PallesenVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Elizabeth M ParzychVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
David B WeinerVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: dweiner@wistar.org.

Funding

TRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · WISTAR INSTITUTE · 1985 to 2025
$3.9M
NCI NIH HHS T32 CA009171
6 · The paper itself

Abstract

Incretin mimetic drugs have transformed the treatment of obesity and type 2 diabetes; however, production and patient compliance challenges remain. Plasmid DNA has recently demonstrated the ability to deliver functional monoclonal antibodies for over a year in human patients. We generated plasmid-encoded long-acting incretins (pLincretins) by fusing cleavage-resistant glucagon-like peptide-1 and gastric inhibitory polypeptide analogues with IgG heavy chain (Fc) components. Plasmids were delivered to diet-induced obese mice using a clinically validated electroporation device. A single administration drove sustained expression, supporting durable reductions in body weight, food intake, and blood glucose. Building on this framework, we used AI-guided protein modeling and a synthetic consensus approach to design a dual glucagon-like peptide-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor agonist [plasmid-encoded synthetic consensus incretin (pSynCretin)]. pSynCretin demonstrated enhanced GLP-1R avidity and induced potent weight loss in vivo. These findings establish DNA-launched incretin mimetics as a potential therapeutic tool that combines the potency of next-generation metabolic hormones with the durability, safety, and translational feasibility of plasmid delivery.

Indexed as

electroporationGIPGLP-1incretin mimeticsobesity therapyplasmid DNA deliverysustained expression

Identifiers

PMID42321077
PMCPMC13380232

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.