Evidence map›Paper›PMID 29077949›Full record

ArticleNucleic acids research2018

Incorporation of aptamers in the terminal loop of shRNAs yields an effective and novel combinatorial targeting strategy.

Ka Ming Pang, Daniela Castanotto, Haitang Li, Lisa Scherer, John J Rossi

Abstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Block and Lock HIV Cure Strategies to Control the Latent Reservoir.Frontiers in cellular and infection microbiology · 2020
    Review
  8. Review
  9. Review
  10. Genetic Strategies for HIV Treatment and Prevention.Molecular therapy. Nucleic acids · 2018
    Review
  11. Review
  12. Review
  13. 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

5 authors.

Ka Ming PangDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Daniela CastanottoDepartment of Medical Oncology & Therapeutics Research, City of Hope National Cancer Center, Duarte, CA 91010, USA.
Haitang LiDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Lisa SchererDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
John J RossiDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
COMBINATORIAL USE OF CCR5 RIBOZYMES WITH ANTI HIV1 RNASR01AI042552 · NIAID · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI ROSSI, JOHN JOSEPH · 1998 to 2019
$7.8M
YEAST SYSTEM FOR DEVELOPING ANTI-HIV-1 RIBOZYMESR01AI029329 · NIAID · LOMA LINDA UNIVERSITY · PI ROSSI, JOHN JOSEPH · 1990 to 2018
$3.9M
NCI NIH HHS P30 CA033572NIAID NIH HHS R01 AI029329NIAID NIH HHS R01 AI042552
6 · The paper itself

Abstract

Gene therapy by engineering patient's own blood cells to confer HIV resistance can potentially lead to a functional cure for AIDS. Toward this goal, we have previously developed an anti-HIV lentivirus vector that deploys a combination of shRNA, ribozyme and RNA decoy. To further improve this therapeutic vector against viral escape, we sought an additional reagent to target HIV integrase. Here, we report the development of a new strategy for selection and expression of aptamer for gene therapy. We developed a SELEX protocol (multi-tag SELEX) for selecting RNA aptamers against proteins with low solubility or stability, such as integrase. More importantly, we expressed these aptamers in vivo by incorporating them in the terminal loop of shRNAs. This novel strategy allowed efficient expression of the shRNA-aptamer fusions that targeted RNAs and proteins simultaneously. Expressed shRNA-aptamer fusions targeting HIV integrase or reverse transcriptase inhibited HIV replication in cell cultures. Viral inhibition was further enhanced by combining an anti-integrase aptamer with an anti-HIV Tat-Rev shRNA. This construct exhibited efficacy comparable to that of integrase inhibitor Raltegravir. Our strategy for the selection and expression of RNA aptamers can potentially extend to other gene therapy applications.

Indexed as

Acquired Immunodeficiency SyndromeAptamers, NucleotideBase SequenceGene Expression Regulation, ViralGenetic TherapyHIV-1HIV InfectionsHIV IntegraseHumansNucleic Acid ConformationProtein BindingRNA-Directed DNA PolymeraseRNA, Small InterferingRNA, ViralVirus ReplicationAptamers, NucleotideHIV IntegraseRNA-Directed DNA PolymeraseRNA, Small InterferingRNA, Viral

Identifiers

PMID29077949
PMCPMC5758892

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.