Evidence map›Paper›PMID 28769791›Full record

ArticleFrontiers in pharmacology2017

Optimized AAV rh.10 Vectors That Partially Evade Neutralizing Antibodies during Hepatic Gene Transfer.

Ruchita Selot, Sathyathithan Arumugam, Bertin Mary, Sabna Cheemadan, Giridhara R Jayandharan

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Evading the AAV Immune Response in Mucopolysaccharidoses.International journal of molecular sciences · 2020
    Review
  13. Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management.International journal of molecular sciences · 2020
    Review
  14. Article
  15. Engineering the AAV capsid to evade immune responses.Current opinion in biotechnology · 2019
    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 at 2 institutions in 1 country.

Ruchita SelotDepartment of Biological Sciences and Bioengineering, Indian Institute of TechnologyKanpur, India.
Sathyathithan ArumugamDepartment of Biological Sciences and Bioengineering, Indian Institute of TechnologyKanpur, India.
Bertin MaryDepartment of Biological Sciences and Bioengineering, Indian Institute of TechnologyKanpur, India.
Sabna CheemadanDepartment of Hematology and Centre for Stem Cell Research (CSCR), Christian Medical CollegeVellore, India.
Giridhara R JayandharanDepartment of Biological Sciences and Bioengineering, Indian Institute of TechnologyKanpur, India.
Indian Institute of Technology Kanpur · INChristian Medical College & Hospital · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Of the 12 common serotypes used for gene delivery applications, Adeno-associated virus (AAV)rh.10 serotype has shown sustained hepatic transduction and has the lowest seropositivity in humans. We have evaluated if further modifications to AAVrh.10 at its phosphodegron like regions or predicted immunogenic epitopes could improve its hepatic gene transfer and immune evasion potential. Mutant AAVrh.10 vectors were generated by site directed mutagenesis of the predicted targets. These mutant vectors were first tested for their transduction efficiency in HeLa and HEK293T cells. The optimal vector was further evaluated for their cellular uptake, entry, and intracellular trafficking by quantitative PCR and time-lapse confocal microscopy. To evaluate their potential during hepatic gene therapy, C57BL/6 mice were administered with wild-type or optimal mutant AAVrh.10 and the luciferase transgene expression was documented by serial bioluminescence imaging at 14, 30, 45, and 72 days post-gene transfer. Their hepatic transduction was further verified by a quantitative PCR analysis of AAV copy number in the liver tissue. The optimal AAVrh.10 vector was further evaluated for their immune escape potential, in animals pre-immunized with human intravenous immunoglobulin. Our results demonstrate that a modified AAVrh.10 S671A vector had enhanced cellular entry (3.6 fold), migrate rapidly to the perinuclear region (1 vs. >2 h for wild type vectors)

Indexed as

AAVB-cellconfocal microscopygene therapyimmune-escapeneutralizing antibodyT-cell

Identifiers

PMID28769791
PMCPMC5511854
OpenAlexW2735234748

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.