Evidence map›Paper›PMID 40809785›Full record

ArticleJournal of molecular and cellular cardiology plus2025

Generation and evaluation of a novel PI3K-targeting gene therapy in the failing mouse heart and healthy sheep heart.

Sebastian Bass-Stringer, Daniel G Donner, Clive N May, Aya Matsumoto, Emma I Masterman, Aascha A D'Elia, Yi Ching Chen, Helen Kiriazis, Jieting Luo, Roger Chooi and 6 more

Abstract read
In one paragraph

Article in Journal of molecular and cellular cardiology plus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Understanding the distinct role of PI3K(p110Frontiers in cardiovascular medicine · 2026
    Review
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

16 authors.

Sebastian Bass-StringerBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Daniel G DonnerBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Clive N MayPreclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC 3010, Australia.
Aya MatsumotoBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Emma I MastermanBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Aascha A D'EliaBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Yi Ching ChenBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Helen KiriazisBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Jieting LuoBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Roger ChooiBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Clara Liu Chung MingHeart Research Institute, Newtown, NSW 2042, Australia.
Paul GregorevicDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia.
Colleen J ThomasDepartment of Microbiology, Anatomy Physiology, and Pharmacology, La Trobe University, Bundoora, VIC 3086, Australia.
Bianca C BernardoBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Kate L WeeksBaker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC 3010, Australia.
Julie R McMullenBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heart failure (HF) remains a clinical challenge with cardiac dysfunction typically progressing even with treatment, and heart transplants only available to small numbers. We previously identified phosphoinositide 3-kinase (PI3K, p110α) as a master regulator of exercise-induced cardioprotection, and showed that gene therapy, incorporating a constitutively active form of PI3K (caPI3K) improved function of the failing mouse heart. However, this approach was not cardiac-specific and the gene therapy was challenging to manufacture. The aim of this study was to develop new PI3K-based gene therapies with more optimal properties for clinical translation. We generated and assessed adeno-associated viruses (AAV6) encoding various PI3K constructs, with different enhancers, promoters and transgene components in healthy adult male mice. The most promising AAV construct based on AAV expression, cardiac-specificity, and ease of manufacture contained a cardiac troponin T (cTnT) promoter together with a small region of the regulatory subunit of PI3K (iSH2), and an intron from the β-globin gene which enhances transcription (IVS2). This AAV (1 × 10

Indexed as

AAVGene therapyHeart failureLarge animalMousePI3K

Identifiers

PMID40809785
PMCPMC12346098

What OpenQuestion 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 OpenQuestion graph.