Evidence map›Paper›PMID 34953085›Full record

ArticleBiotechnology and bioengineering2022

Restoration of DNA repair mitigates genome instability and increases productivity of Chinese hamster ovary cells.

Philipp N Spahn, Xiaolin Zhang, Qing Hu, Huiming Lu, Nathaniel K Hamaker, Hooman Hefzi, Shangzhong Li, Chih-Chung Kuo, Yingxiang Huang, Jamie C Lee and 4 more

Open access · greenAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.2field-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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. CRISPR Technologies in Chinese Hamster Ovary Cell Line Engineering.International journal of molecular sciences · 2023
    Review
  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

14 authors at 4 institutions in 1 country.

Philipp N SpahnDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Xiaolin ZhangDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.
Qing HuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Huiming LuDepartment of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Nathaniel K HamakerDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.
Hooman HefziDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.
Shangzhong LiDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0003-0272-3942
Chih-Chung KuoDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.
Yingxiang HuangDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Jamie C LeeDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Anthony J DavisDepartment of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Peter LyDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Kelvin H LeeDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.
Nathan E LewisDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0003-0973-0571
University of California San Diego · USThe University of Texas Southwestern Medical Center · USUniversity of Delaware · USFoundation Center · US

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
CELLULAR FUNCTIONS OF EUKARYOTIC LIGASESR01GM047251 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI DAVIS, ANTHONY J, TOMKINSON, ALAN E · 1998 to 2021
$4.7M
Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3M
Pathway Choice of DNA Double-Strand Break RepairR01CA162804 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI DAVIS, ANTHONY J · 2012 to 2021
$3.4M
NCI NIH HHS R01 CA162804NIGMS NIH HHS R01 GM047251NIGMS NIH HHS R35 GM119850NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Chinese hamster ovary (CHO) cells are the primary host for manufacturing of therapeutic proteins. However, productivity loss is a major problem and is associated with genome instability, as chromosomal aberrations reduce transgene copy number and decrease protein expression. We analyzed whole-genome sequencing data from 11 CHO cell lines and found deleterious single-nucleotide variants in DNA repair genes. Comparison with primary Chinese hamster cells confirmed DNA repair to be compromised in CHO. Correction of key DNA repair genes by single-nucleotide variant reversal or expression of intact complementary DNAs successfully improved DNA repair and mitigated karyotypic instability. Moreover, overexpression of intact copies of LIG4 and XRCC6 in a CHO cell line expressing secreted alkaline phosphatase mitigated transgene copy loss and improved protein titer retention. These results show that correction of DNA repair genes yields improvements in genome stability in CHO, and provide new opportunities for cell line development for sustainable protein expression.

Indexed as

DNA RepairGenomic InstabilityAnimalsCHO CellsCricetinaeCricetulusKaryotypingcell line instabilityCHODNA repairprotein expression

Identifiers

PMID34953085
PMCPMC8821244
OpenAlexW4200573925

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.