Evidence map›Paper›PMID 30514969›Full record

ArticleGene therapy2019

Immunosuppression overcomes insulin- and vector-specific immune responses that limit efficacy of AAV2/8-mediated insulin gene therapy in NOD mice.

Asha Recino, Shu Uin Gan, Kian Chuan Sia, Yvonne Sawyer, Jenny Trendell, Richard Kay, Fiona M Gribble, Frank Reimann, Rob Foale, Maria Notaridou and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 19% of its field
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

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020
    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

17 authors at 4 institutions in 2 countries.

Asha RecinoDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. ar633@cam.ac.uk.
Shu Uin GanDepartment of Surgery, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-9672-0306
Kian Chuan SiaDepartment of Surgery, National University of Singapore, Singapore, Singapore.
Yvonne SawyerDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
Jenny TrendellDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
Richard KayInstitute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Fiona M GribbleInstitute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.ORCID http://orcid.org/0000-0002-4232-2898
Frank ReimannInstitute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.ORCID http://orcid.org/0000-0001-9399-6377
Rob FoaleDick White Referrals, Station Farm, Six Mile Bottom, Suffolk, UK.
Maria NotaridouDepartment of Haematology, UCL Cancer Institute, London, UK.
Nick HolmesDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
Andrew LeverDepartment of Medicine, University of Cambridge, Cambridge, UK.
Kok Onn LeeDepartment of Medicine, National University of Singapore, Singapore, Singapore.
Amit NathwaniDepartment of Haematology, UCL Cancer Institute, London, UK.
Anne CookeDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.ORCID http://orcid.org/0000-0003-3327-6081
Roy CalneDepartment of Surgery, National University of Singapore, Singapore, Singapore.
Maja WallbergDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. mw394@cam.ac.uk.
University of Cambridge · GBNational University of Singapore · SGAddenbrooke's Hospital · GBCRUK Lung Cancer Centre of Excellence · GB

Funding

Department of Health RP-PG-0310-1001Medical Research Council G0502121Medical Research Council G0902219Medical Research Council MC_UU_00014/3Medical Research Council MC_UU_00014/5Medical Research Council MC_UU_12012/1Medical Research Council MC_UU_12012/3Medical Research Council MC_UU_12012/5Medical Research Council MR/L013185/1Medical Research Council MR/M009041/1Medical Research Council MR/M024873/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/M001083/1Wellcome TrustWellcome Trust 106262/Z/14/ZWellcome Trust 106 263/Z/14/Z
6 · The paper itself

Abstract

We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontaneously diabetic Non Obese Diabetic (NOD) mice by intravenous systemic administration of a single-stranded adeno-associated virus (ssAAV2/8) codon optimised (co) vector encoding furin cleavable human proinsulin under a liver-specific promoter. There were no immunological barriers to efficacy of insulin gene therapy in chemically induced C57BL/6 mice, which enjoyed long-lasting correction of hyperglycaemia after therapy, up to 250 days. Euglycaemia was also restored in spontaneously diabetic NOD mice, although these mice required a 7-10-fold higher dose of vector to achieve similar efficacy as the C57BL/6 mice and the immunodeficient NOD

Indexed as

AnimalsCD4 AntigensDependovirusDiabetes Mellitus, ExperimentalGenetic TherapyHEK293 CellsHumansImmunosuppression TherapyInsulinLiverMaleMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDT-LymphocytesCD4 AntigensInsulin

Identifiers

PMID30514969
PMCPMC6514884
OpenAlexW2902289040

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.