Evidence map›Paper›PMID 33293555›Full record

ArticleNature communications2020

Design of efficacious somatic cell genome editing strategies for recessive and polygenic diseases.

Jared Carlson-Stevermer, Amritava Das, Amr A Abdeen, David Fiflis, Benjamin I Grindel, Shivani Saxena, Tugce Akcan, Tausif Alam, Heidi Kletzien, Lucille Kohlenberg and 3 more

Open access · goldAbstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-weighted citation impact, top 11% 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, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. 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

13 authors at 1 institution in 1 country.

Jared Carlson-StevermerWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Amritava DasWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Amr A AbdeenWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
David FiflisWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Benjamin I GrindelWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Shivani SaxenaWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Tugce AkcanDepartment of Surgery, University of Wisconsin-Madison, Madison, WI, USA.
Tausif AlamDepartment of Surgery, University of Wisconsin-Madison, Madison, WI, USA.
Heidi KletzienDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Lucille KohlenbergWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Madelyn GoedlandWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Micah J DombroeWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
Krishanu SahaWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.ORCID 0000-0003-2837-0858
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Justine Yang Bruce · 1985 to 2026
$142.6M
Assembly of Novel Gene Editing Particles to Understand Genome Surgery in Patient-Derived CellsR35GM119644 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SAHA, KRISHANU · 2016 to 2025
$4.0M
NCI NIH HHS P30 CA014520NIGMS NIH HHS R35 GM119644
6 · The paper itself

Abstract

Compound heterozygous recessive or polygenic diseases could be addressed through gene correction of multiple alleles. However, targeting of multiple alleles using genome editors could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that Cas9-ribonucleoprotein-based genome editors can correct two distinct mutant alleles within a single human cell precisely. Gene-corrected cells in an induced pluripotent stem cell model of Pompe disease expressed the corrected transcript from both corrected alleles, leading to enzymatic cross-correction of diseased cells. Using a quantitative in silico model for the in vivo delivery of genome editors into the developing human infant liver, we identify progenitor targeting, delivery efficiencies, and suppression of imprecise editing outcomes at the on-target site as key design parameters that control the efficacy of various therapeutic strategies. This work establishes that precise gene editing to correct multiple distinct gene variants could be highly efficacious if designed appropriately.

Indexed as

AllelesCells, CulturedComputer SimulationCRISPR-Cas SystemsGene EditingGenetic TherapyGene Transfer TechniquesGlycogen Storage Disease Type IIHumansInduced Pluripotent Stem CellsInfantInheritance PatternsLiverMaleModels, GeneticMutation

Identifiers

PMID33293555
PMCPMC7722885
OpenAlexW3112830125

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.