Evidence map›Paper›PMID 29216761›Full record

ArticleHuman gene therapy2018

Efficient Therapeutic Protein Expression Using Retroviral Replicating Vector with 2A Peptide in Cancer Models.

Andrew Hofacre, Kader Yagiz, Daniel Mendoza, Fernando Lopez Espinoza, Anthony W Munday, Cynthia Burrascano, Oded Singer, Harry E Gruber, Douglas J Jolly, Amy H Lin

Abstract read
In one paragraph

Article in Human gene therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 16% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. AAV-PHP.eB Peripheral Delivery and Central Expression in Cre Mice.The Journal of comparative neurology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Synthetic polycistronic sequences in eukaryotes.Synthetic and systems biotechnology · 2021
    Review
  6. Review
  7. Review
  8. Article
  9. Article
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

10 authors at 1 institution in 1 country.

Andrew HofacreTocagen, Inc. , San Diego, California.
Kader YagizTocagen, Inc. , San Diego, California.
Daniel MendozaTocagen, Inc. , San Diego, California.
Fernando Lopez EspinozaTocagen, Inc. , San Diego, California.
Anthony W MundayTocagen, Inc. , San Diego, California.
Cynthia BurrascanoTocagen, Inc. , San Diego, California.
Oded SingerTocagen, Inc. , San Diego, California.
Harry E GruberTocagen, Inc. , San Diego, California.
Douglas J JollyTocagen, Inc. , San Diego, California.
Amy H LinTocagen, Inc. , San Diego, California.
ToolGen (South Korea) · KR

Funding

Translational Development of Replication-Competent Retrovirus VectorsU01NS059821 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KASAHARA, NORIYUKI · 2010 to 2013
$2.9M
Combining Virotherapy and Immunotherapy for CancerR01CA105171 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KASAHARA, NORIYUKI · 2004 to 2008
$1.5M
NCI NIH HHS R01 CA105171NINDS NIH HHS U01 NS059821
6 · The paper itself

Abstract

Toca 511, a retroviral replicating vector (RRV), uses an internal ribosomal entry site (IRES) to express an optimized yeast cytosine deaminase (yCD2), which converts 5-fluorocytosine to 5-fluorouracil. This configuration is genetically stable in both preclinical mouse models and human clinical trials. However, the use of IRES (∼600 bp) restricts choices of therapeutic transgenes due to limits in RRV genome size. This study replaced IRES with 2A peptides derived from picornaviruses with or without a GSG linker. The data show that GSG-linked 2A (g2A) peptide resulted in higher polyprotein separation efficiency than non-GSG linked 2A peptide. The study also shows that RRV can tolerate insertion of two separate 2A peptides to allow expression of two transgenes without compromising the assembly and function of the virus in addition to insertion of a single 2A peptide to confirm genetic stability with yCD2, green fluorescent protein, and HSV-1 thymidine kinase. In a parallel comparison of the RRV-IRES-yCD2 and RRV-g2A-yCD2 configurations, the study shows the yCD2 protein expressed from RRV-g2A-yCD2 has higher activity, resulting in a higher survival benefit in an intracranial tumor mouse model. These data enable a wider range of potential product candidates that could be developed using the RRV platform.

Indexed as

Genetic TherapyGenetic VectorsAnimalsBrain NeoplasmsCytosine DeaminaseDisease Models, AnimalGreen Fluorescent ProteinsHumansInternal Ribosome Entry SitesMicePeptidesPicornaviridaeVirus ReplicationXenograft Model Antitumor AssaysCytosine DeaminaseGreen Fluorescent ProteinsInternal Ribosome Entry SitesPeptides2A peptidecancer gene therapyretroviral replicating vector

Identifiers

PMID29216761
PMCPMC6422008
OpenAlexW2773964739

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.