Evidence map›Paper›PMID 32671135›Full record

ArticleMolecular therapy. Methods & clinical development2020

Effects of Thermally Induced Configuration Changes on rAAV Genome's Enzymatic Accessibility.

Yinxia Xu, Ping Guo, Junping Zhang, Matthew Chrzanowski, Helen Chew, Jenni A Firrman, Nianli Sang, Yong Diao, Weidong Xiao

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2020. 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
1.6field-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

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. 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

9 authors at 5 institutions in 2 countries.

Yinxia XuSchool of Biomedical Science, Huaqiao University, Quanzhou, China.
Ping GuoSchool of Biomedical Science, Huaqiao University, Quanzhou, China.
Junping ZhangHerman B Wells Center for Pediatric Research, Indiana University, Indianapolis, IN 46202, USA.
Matthew ChrzanowskiTemple University Medical School, Philadelphia, PA 19140, USA.
Helen ChewTemple University Medical School, Philadelphia, PA 19140, USA.
Jenni A FirrmanUnited States Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, Wyndmoor, PA 19038, USA.
Nianli SangDepartment of Biology, College of Arts and Sciences, Drexel University, Philadelphia, PA 19104, USA.
Yong DiaoSchool of Biomedical Science, Huaqiao University, Quanzhou, China.
Weidong XiaoHerman B Wells Center for Pediatric Research, Indiana University, Indianapolis, IN 46202, USA.
Huaqiao University · CNIndiana University – Purdue University Indianapolis · USTemple University · USAgricultural Research Service · USDrexel University · US

Funding

Temple Project 1: Genetic characterization of factor VIII Inhibitors and glydosylation patternsU54HL142019 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI LI, LEI, MIAO, CAROL H · 2018 to 2022
$6.9M
Novel adeno-associated virus vector production system developmentR01HL114152 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAO, WEIDONG · 2012 to 2016
$2.2M
Development of highly efficient factor VIII mini-gene therapyR01HL130871 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAO, WEIDONG · 2016 to 2019
$1.9M
NHLBI NIH HHS R01 HL114152NHLBI NIH HHS R01 HL130871NHLBI NIH HHS U54 HL142019
6 · The paper itself

Abstract

Physical titers for recombinant adeno-associated viral (rAAV) vectors are measured by quantifying viral genomes. It is generally perceived that AAV virions disassemble and release DNA upon thermal treatment. Here, we present data on enzymatic accessibility of rAAV genomes when AAV virions were subjected to thermal treatment. For rAAV vectors with a normal genome size (≤4.7 kb), thermal treatment at 75°C-99°C allowed only ∼10% of genomes to be detectable by quantitative real-time PCR. In contrast, greater than 70% of AAV genomes can be detected under similar conditions for AAV vectors with an oversized genome (≥5.0 kb). The permeability of virions, as measured by ethidium bromide (EB) staining, was enhanced by thermal stimulation. These results suggest that in rAAV virions with standard-sized genomes, the capsid and DNA are close enough in proximity for heat-induced "crosslinking," which results in inaccessibility of vector DNA to enzymatic reactions. In contrast, rAAV vectors with oversized genomes release their DNA readily upon thermal treatment. These findings suggested that the spatial arrangement of capsid protein and DNA in AAV virions is genome-size dependent. These results provide a foundation for future improvement of vector assays, design, and applications.

Identifiers

PMID32671135
PMCPMC7338580
OpenAlexW3034789387

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.