Evidence map›Paper›PMID 38108975›Full record

ArticleMethods in molecular biology (Clifton, N.J.)2024

Monitoring the Secretion and Activity of Alpha-1 Antitrypsin in Various Mammalian Cell Types.

Kevin P Guay, Haiping Ke, Lila M Gierasch, Anne Gershenson, Daniel N Hebert

Open access · greenAbstract read
In one paragraph

Article in Methods in molecular biology (Clifton, N.J.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. 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 1 institution in 1 country.

Kevin P GuayDepartment of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA.
Haiping KeDepartment of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA.
Lila M GieraschDepartment of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA.
Anne GershensonDepartment of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA.
Daniel N HebertDepartment of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA. dhebert@biochem.umass.edu.
University of Massachusetts Amherst · US

Funding

Protein folding in the cell: Challenges and coping mechanisms Administrative Supplement for Equipment PurchaseR35GM118161 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI GIERASCH, LILA M · 2016 to 2025
$5.5M
Cellular protein maturation and degradationR01GM086874 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI RAUCH, JENNIFER NICOLE · 2009 to 2025
$4.5M
CHEMISTRY-BIOLOGY INTERFACE PREDOCTORAL TRAINING GRANTST32GM008515 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI THOMPSON, LYNMARIE K. · 1995 to 2020
$4.3M
Chemistry-Biology Interface Predoctoral Training GrantT32GM139789 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI ERIC Robert STRIETER · 2021 to 2026
$3.4M
NIGMS NIH HHS R01 GM086874NIGMS NIH HHS R35 GM118161NIGMS NIH HHS T32 GM008515NIGMS NIH HHS T32 GM139789
6 · The paper itself

Abstract

Overexpression of recombinant protein in mammalian cells is widely used for producing biologics, as protein maturation and post-translational modifications are similar to human cells. Some therapeutics, such as mRNA vaccines, target nonnative cells that may contain inefficient secretory machinery. For example, gene replacement therapies for alpha-1 antitrypsin (AAT), a glycoprotein normally produced in hepatocytes, are often targeted to muscle cells due to ease of delivery. In this chapter, we define methods for expressing AAT in representative cell types such as Huh-7; hepatocytes; Chinese hamster ovarian cells (CHO), a common host to produce biologics; and C2C12, a muscle progenitor cell line. Methods for metabolically labeling AAT to monitor secretion in these cell lines are described along with the use of proteostasis activators to increase the amount of AAT secreted in both C2C12 myoblasts and differentiated myotubes. Assays to assess the activity and glycan composition of overexpressed AAT are also presented. The usage of the proteostasis activator SAHA provided a 40% improvement in expression of active AAT in muscle-like cells and may be an advantageous adjuvant for recombinant production of proteins delivered by mRNA vaccines.

Indexed as

Biological ProductsmRNA VaccinesAnimalsCHO CellsCricetinaeHepatocytesHumansMammalsMuscle Fibers, SkeletalBiological ProductsmRNA VaccinesAlpha-1 antitrypsin (AAT)GlycansImmunoprecipitationMammalian cellsMetabolic labelingProtein secretionProteostasis activators

Identifiers

PMID38108975
PMCPMC10918612
OpenAlexW4389895345

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.