Evidence map›Paper›PMID 10505109›Full record

ArticleGene therapy1999

Sustained gene expression in transplanted skin fibroblasts in rats.

M Q Wei, D V Lejnieks, N Ramesh, S Lau, J Seppen, W R Osborne

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Gene therapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.4field-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

1 citing paper in PubMed, 10 citations in OpenAlex.

  1. Gene silencing as a threat to the success of gene therapy.The Journal of clinical investigation · 2000
    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

6 authors at 1 institution in 1 country.

M Q WeiDepartment of Pediatrics, University of Washington, Seattle 98195, USA.
D V Lejnieks
N Ramesh
S Lau
J Seppen
W R Osborne
University of Washington · US

Funding

PILOT STUDY--RETROVIRUS MEDIATED TRANSFER OF HUMAN GLUCOCEREBROSIDASE GENEP30DK047754 · NIDDK · UNIVERSITY OF WASHINGTON · PI KIEM, HANS-PETER · 1994 to 2008
$8.4M
CANINE G-CSF GENE TRANSFERR01DK043727 · NIDDK · UNIVERSITY OF WASHINGTON · PI OSBORNE, WILLIAM R · 1992 to 2007
$1.3M
CLINICAL MODEL OF ERYTHROPOIETIN GENE THERAPYR01DK050686 · NIDDK · UNIVERSITY OF WASHINGTON · PI OSBORNE, WILLIAM R · 1996 to 1999
–
NIDDK NIH HHS DK 43727NIDDK NIH HHS DK 47754NIDDK NIH HHS DK 50686
6 · The paper itself

Abstract

Retrovirus-mediated gene transfer into adult skin fibroblasts has provided measurable amounts of therapeutic proteins in animal models. However, the major problem emerging from these experiments was a limited time of vector encoded gene expression once transduced cells were engrafted. We hypothesized that sustained transduced gene expression in quiescent fibroblasts in vivo might be obtained by using a fibronectin (Fn) promoter. Fibronectin plays a key role in cell adhesion, migration and wound healing and is up-regulated in quiescent fibroblasts. Retroviral vectors containing human adenosine deaminase (ADA) cDNA linked to rat fibronectin promoter (LNFnA) or viral LTR promoter (LASN) were compared for their ability to express ADA from transduced primary rat skin fibroblasts in vivo. Skin grafts formed from fibroblasts transduced with LNFnA showed strong human ADA enzyme activity from 1 week to 3 months. In contrast, skin grafts containing LASN-transduced fibroblasts tested positive for human ADA for weeks 1 and 2, were faintly positive at week 3 and showed no human ADA expression at 1, 2 and 3 months. Thus, a fibronectin promoter provided sustained transduced gene expression at high levels for at least 3 months in transplanted rat skin fibroblasts, perhaps permitting the targeting of this tissue for human gene therapy.

Indexed as

Adenosine DeaminaseAnimalsCells, CulturedDNAFibroblastsFibronectinsGene ExpressionGenetic TherapyGenetic VectorsHumansPromoter Regions, GeneticRatsRats, Inbred F344Regulatory Sequences, Nucleic AcidRetroviridaeTime FactorsAdenosine DeaminaseDNAFibronectins

Identifiers

PMID10505109
OpenAlexW1969458179

What OpenQuestion holds

Textmetadata
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.