Evidence map›Paper›PMID 42005833›Full record

ArticleMolecular therapy. Oncology2026

AAV immuno-gene therapy platform delivering vectorized cytokines defines a new modality for high-grade glioma treatment.

Akela Kuwahara, Ethan M Fenton, Chris Lovejoy, Tian Lee, Lin Wang, Miko Fogarty, Jangham Jung, Syuan-Ming Guo, Lucy H Maynard, Andrew P May and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Oncology, 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

17 authors.

Akela KuwaharaSiren Biotechnology, Inc., San Francisco, CA 94107, USA.
Ethan M FentonSiren Biotechnology, Inc., San Francisco, CA 94107, USA.
Chris LovejoySiren Biotechnology, Inc., San Francisco, CA 94107, USA.
Tian LeeSiren Biotechnology, Inc., San Francisco, CA 94107, USA.
Lin WangDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
Miko FogartyDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
Jangham JungDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
Syuan-Ming GuoChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Lucy H MaynardChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Andrew P MayChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Yael Rossenberg-HassonInstitute for Immunity, Transplantation & Infection, Stanford University, Stanford, CA 94305, USA.
Jennifer L ClarkeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
Aaron A DiazDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
Joanna J PhillipsDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
Lauren KellySiren Biotechnology, Inc., San Francisco, CA 94107, USA.
Nathalie ClémentSiren Biotechnology, Inc., San Francisco, CA 94107, USA.
Nicole K PaulkSiren Biotechnology, Inc., San Francisco, CA 94107, USA.

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Overcoming sexually dimorphic barriers to viral gene therapy for treating genetic liver diseases.K01DK107607 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PAULK, NICOLE K · 2016 to 2020
$782k
NCI NIH HHS P50 CA097257NIDDK NIH HHS K01 DK107607
6 · The paper itself

Abstract

High-grade gliomas are among the most treatment-refractory solid tumors, with profound immunosuppression, diffuse infiltration, and resistance to existing immunotherapies. Interferons (IFNs) have potent anti-tumor and immunostimulatory activities, but systemic IFN therapies have failed in solid tumors due to poor pharmacokinetics and dose-limiting toxicities. Here, we introduce vectorized IFNs (recombinant adeno-associated virus [AAV] gene therapies enabling sustained, localized IFN expression within tumors) as a new class of biologics for high-grade glioma treatment. We engineered AAV vectors expressing human IFNα1, IFNβ, IFNγ, or combinations thereof and demonstrated potent, selective anti-tumor activity in patient-derived glioblastoma organoids while sparing healthy brain cells. Transcriptomic profiling revealed a durable, IFN-specific response in treated tumor cells. AAV-hIFNβ was advanced to orthotopic patient-derived and cell line-derived xenograft models, where intratumoral convection-enhanced delivery produced complete tumor clearance and significantly prolonged survival. Spatial transcriptomic and histologic analyses showed tumor-localized IFN expression, immune activation, and apoptosis-mediated tumor regression. To enable clinical translation, we developed SRN-101, a clinical-grade AAV-hIFNβ construct with optimized potency and manufacturability, which achieved superior expression and

Indexed as

AAVconvection-enhanced deliverycytokineglioblastomahigh-grade gliomaimmuno-gene therapyimmunotherapyinterferon betaMT: Regular IssueSRN-101tumor microenvironment

Identifiers

PMID42005833
PMCPMC13091051

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Registered trials

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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.