Evidence map›Paper›PMID 25917932›Full record

ArticleThe journal of gene medicine

Adeno-associated virus mediated delivery of an engineered protein that combines the complement inhibitory properties of CD46, CD55 and CD59.

Derek Leaderer, Siobhan M Cashman, Rajendra Kumar-Singh

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of gene medicine. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Navigating the Hurdles of Intra-Articular AAV Gene Therapy.International journal of molecular sciences · 2025
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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

3 authors at 1 institution in 1 country.

Derek LeadererDepartment of Developmental, Molecular and Chemical Biology, Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
Siobhan M CashmanDepartment of Developmental, Molecular and Chemical Biology, Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
Rajendra Kumar-SinghDepartment of Developmental, Molecular and Chemical Biology, Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
Tufts University · US

Funding

Gene Therapy for Retinitis PigmentosaR01EY013837 · NEI · UNIVERSITY OF UTAH · PI KUMAR-SINGH, RAJENDRA · 2003 to 2012
$2.7M
Non-Viral Gene Therapy for Retinal DegenerationR01EY021805 · NEI · TUFTS UNIVERSITY BOSTON · PI KUMAR-SINGH, RAJENDRA · 2011 to 2014
$1.8M
NEI NIH HHS EY013837NEI NIH HHS EY021805NEI NIH HHS R01 EY013837NEI NIH HHS R01 EY021805
6 · The paper itself

Abstract

backgroundA variety of disorders are associated with the activation of complement. CD46, CD55 and CD59 are the major membrane associated regulators of complement on human cells. Previously, we have found that independent expression of CD55, CD46 or CD59 through gene transfer protects murine tissues against human complement mediated attack. In the present study, we investigated the potential of combining the complement regulatory properties of CD46, CD55 and CD59 into single gene products expressed from an adeno-associated virus (AAV) vector in a soluble non-membrane anchored form.

methodsMinigenes encoding the complement regulatory domains from CD46, CD55 and CD59 (SACT) or CD55 and CD59 (DTAC) were cloned into an AAV vector. The specific regulatory activity of each component of SACT and DTAC was measured in vitro. The recombinant AAV vectors were injected into the peritoneum of mice and the efficacy of the transgene products for being able to protect murine liver vasculature against human complement, specifically the membrane attack complex (MAC), was measured.

resultsSACT and DTAC exhibited properties similar to CD46, CD55 and CD59 or CD55 and CD59, respectively, in vitro. AAV mediated delivery of SACT or DTAC protected murine liver vasculature from human MAC deposition by 63.2% and 56.7%, respectively.

conclusionsWhen delivered to mice in vivo via an AAV vector, SACT and DTAC are capable of limiting human complement mediated damage. SACT and DTAC merit further study as potential therapies for complement mediated disorders when delivered via a gene therapy approach.

Indexed as

Complement Inactivating AgentsTransgenesAnimalsCD55 AntigensCD59 AntigensComplement ActivationDependovirusGenetic VectorsHumansMembrane Cofactor ProteinMiceProtein Structure, TertiaryCD55 AntigensCD59 AntigensComplement Inactivating AgentsMembrane Cofactor ProteinAAVCD46CD55CD59complement systemgene therapy

Identifiers

PMID25917932
PMCPMC4682684
OpenAlexW1570096727

What OpenQuestion holds

Textmetadata
LicenceTDM
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.