Evidence map›Paper›PMID 16810196›Full record

ArticleGene therapy2006

Use of synthetic vectors for neutralising antibody resistant delivery of replicating adenovirus DNA.

R C Carlisle, S S Briggs, A B Hale, N K Green, K D Fisher, T Etrych, K Ulbrich, V Mautner, L W Seymour

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

3 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Myeloma xenograft destruction by a nonviral vector delivering oncolytic infectious nucleic acid.Molecular therapy : the journal of the American Society of Gene Therapy · 2011
    Article
  3. Viruses as anticancer drugs.Trends in pharmacological sciences · 2007
    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

9 authors at 4 institutions in 2 countries.

R C CarlisleDepartment of Clinical Pharmacology, Oxford University, Radcliffe Infirmary, Oxford, UK.
S S Briggs
A B Hale
N K Green
K D Fisher
T Etrych
K Ulbrich
V Mautner
L W Seymour
University of Oxford · GBCzech Academy of Sciences, Institute of Macromolecular Chemistry · CZHybrid Instruments (United Kingdom) · GBUniversity of Birmingham · GB

Funding

Biotechnology and Biological Sciences Research Council BB/C515871/1
6 · The paper itself

Abstract

Use of synthetic vectors to deliver genomes of conditionally replicating lytic viruses combines the strengths of viral and non-viral approaches by enabling neutralising antibody resistant deployment of cancer virotherapy. Adenovirus is particularly suitable for this application since all proteins essential for replication can be expressed from the input DNA, although the presence of terminal protein (TP) covalently linked to the 5' termini of the input virus genomes both improves expression of transgenes encoded in the input DNA and also enhances replication. These roles of TP were distinguished in experiments where E1-deleted Ad(GFP)DNA bearing TP (Ad(GFP)DNA-TP), delivered with DOTAP, gave a two-fold greater frequency of transduction than Ad(GFP)DNA(without TP) in non-complementing A549 cells, while in 293 cells (which support replication of E1-deleted viruses) the presence of TP mediated a much greater differential transgene expression, commensurate with its ability to promote replication. Subsequent studies using AdDNA for virotherapy, therefore, included covalently linked TP. AdDNA-TP delivered to A549 cells using a synthetic polyplex vector was shown to be resistant to levels of neutralising antisera that completely ablated infection by wild-type adenovirus, enabling polyplex/Ad(wild type)DNA-TP to mediate a powerful cytopathic effect. Similarly in vivo, direct injection of a polyplex/Ad(wild type)DNA-TP into A549 tumours was neutralising antibody-resistant and enabled virus replication, whereas intact virus was neutralised by the antibody and failed to infect. The delivery of adenovirus genomes-TP using synthetic vectors should provide a strategy to bypass neutralising antibodies and facilitate clinical application of replicating adenovirus for cancer virotherapy.

Indexed as

AdenoviridaeAnimalsAntibodies, ViralAntigen-Antibody ReactionsDNA, ViralGenetic EngineeringGenetic TherapyMiceMice, SCIDNeoplasmsNeoplasm TransplantationTransduction, GeneticTransfectionVaccines, SyntheticAntibodies, ViralDNA, ViralVaccines, Synthetic

Identifiers

PMID16810196
OpenAlexW2324645219

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.