Evidence map›Paper›PMID 31807699›Full record

ArticleScience advances2019

Durable multitransgene expression in vivo using systemic, nonviral DNA delivery.

Chakkrapong Handumrongkul, Alice L Ye, Stephen A Chmura, Liliana Soroceanu, Marissa Mack, Ryan J Ice, Robert Thistle, Methawee Myers, Sarah J Ursu, Yong Liu and 5 more

Abstract read
In one paragraph

Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

15 authors.

Chakkrapong HandumrongkulDNARx LLC, San Francisco, CA, USA.ORCID 0000-0001-6089-5000
Alice L YeDNARx LLC, San Francisco, CA, USA.ORCID 0000-0003-1128-1074
Stephen A ChmuraDNARx LLC, San Francisco, CA, USA.ORCID 0000-0001-9857-2506
Liliana SoroceanuCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.
Marissa MackDNARx LLC, San Francisco, CA, USA.ORCID 0000-0002-4269-7868
Ryan J IceCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.
Robert ThistleCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.ORCID 0000-0002-9268-2824
Methawee MyersDNARx LLC, San Francisco, CA, USA.
Sarah J UrsuCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.
Yong LiuDNARx LLC, San Francisco, CA, USA.
Mohammed Kashani-SabetCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.
Timothy D HeathDNARx LLC, San Francisco, CA, USA.ORCID 0000-0001-6595-7901
Denny LiggittDepartment of Comparative Medicine, University of Washington, Seattle, WA, USA.
David B LewisDepartment of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.ORCID 0000-0001-7181-0105
Robert DebsDNARx LLC, San Francisco, CA, USA.ORCID 0000-0001-9929-6267

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recombinant adeno-associated virus (AAV) vectors are transforming therapies for rare human monogenic deficiency diseases. However, adaptive immune responses to AAV and its limited DNA insert capacity, restrict their therapeutic potential. HEDGES (high-level extended duration gene expression system), a nonviral DNA- and liposome-based gene delivery platform, overcomes these limitations in immunocompetent mice. Specifically, one systemic HEDGES injection durably produces therapeutic levels of transgene-encoded human proteins, including FDA-approved cytokines and monoclonal antibodies, without detectable integration into genomic DNA. HEDGES also controls protein production duration from <3 weeks to >1.5 years, does not induce anti-vector immune responses, is reexpressed for prolonged periods following reinjection, and produces only transient minimal toxicity. HEDGES can produce extended therapeutic levels of multiple transgene-encoded therapeutic human proteins from DNA inserts >1.5-fold larger than AAV-based therapeutics, thus creating combinatorial interventions to effectively treat common polygenic diseases driven by multigenic abnormalities.

Indexed as

Gene Transfer TechniquesTransgenesAnimalsCell LineDNAFemaleHumansMiceMice, Inbred ICRDNA

Identifiers

PMID31807699
PMCPMC6881169

What OpenQuestion holds

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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.