Evidence map›Paper›PMID 33958732›Full record

ArticleGene therapy2022

Membrane-bound MMP-14 protease-activatable adeno-associated viral vectors for gene delivery to pancreatic tumors.

Susan S Butler, Kenjiro Date, Takashi Okumura, Cooper Lueck, Bidyut Ghosh, Anirban Maitra, Junghae Suh

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 41% 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

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Article
  2. 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

7 authors at 2 institutions in 1 country.

Susan S ButlerDepartment of Bioengineering, Rice University, Houston, TX, USA.
Kenjiro DateDepartments of Translational Molecular Pathology and Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Takashi OkumuraDepartments of Translational Molecular Pathology and Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cooper LueckDepartment of Bioengineering, Rice University, Houston, TX, USA.ORCID 0000-0001-8567-3658
Bidyut GhoshDepartments of Translational Molecular Pathology and Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anirban MaitraDepartments of Translational Molecular Pathology and Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Junghae SuhDepartment of Bioengineering, Rice University, Houston, TX, USA. jsuh@rice.edu.ORCID 0000-0001-9280-9031
The University of Texas MD Anderson Cancer Center · USRice University · US

Funding

Project 3: Inhibiting Oxidative Phosphorylation in Pancreatic CancerP50CA221707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT, MAITRA, ANIRBAN · 2019 to 2023
$11.0M
Interdisciplinary Translational Pre/Postdoctoral Program in Cancer NanotechnologyT32CA196561 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Gang Bao, Konstantin V Sokolov · 2015 to 2026
$3.0M
Translational Applications in an Animal Model of Pancreatic Cystic Neoplasm and CancerR01CA218004 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MAITRA, ANIRBAN · 2018 to 2021
$2.4M
Wnt/?-catenin Signaling in Pancreatic OncogenesisR01CA220236 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MAITRA, ANIRBAN · 2017 to 2023
$1.8M
Provectors for treatment of ovarian cancerR01CA207497 · NCI · RICE UNIVERSITY · PI BAO, GANG, SUH, JUNGHAE · 2016 to 2020
$1.8M
NCI NIH HHS P50 CA221707NCI NIH HHS R01 CA207497NCI NIH HHS R01 CA218004NCI NIH HHS R01 CA220236NCI NIH HHS T32 CA196561
6 · The paper itself

Abstract

Adeno-associated virus' (AAV) relatively simple structure makes it accommodating for engineering into controllable delivery platforms. Cancer, such as pancreatic ductal adenocarcinoma (PDAC), are often characterized by upregulation of membrane-bound proteins, such as MMP-14, that propagate survival integrin signaling. In order to target tumors, we have engineered an MMP-14 protease-activatable AAV vector that responds to both membrane-bound and extracellularly active MMPs. This "provector" was generated by inserting a tetra-aspartic acid inactivating motif flanked by the MMP-14 cleavage sequence IPESLRAG into the capsid subunits. The MMP-14 provector shows lower background transduction than previously developed provectors, leading to a 9.5-fold increase in transduction ability. In a murine model of PDAC, the MMP-14 provector shows increased delivery to an allograft tumor. This proof-of-concept study illustrates the possibilities of membrane-bound protease-activatable gene therapies to target tumors.

Indexed as

Genetic VectorsPancreatic NeoplasmsAnimalsDependovirusGene Transfer TechniquesMatrix Metalloproteinase 14Matrix MetalloproteinasesMicePeptide HydrolasesMatrix Metalloproteinase 14Matrix MetalloproteinasesPeptide Hydrolases

Identifiers

PMID33958732
PMCPMC8571120
OpenAlexW3158383055

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.