Evidence map›Paper›PMID 28374766›Full record

ArticleScientific reports2017

Reprogramming MHC specificity by CRISPR-Cas9-assisted cassette exchange.

William Kelton, Ann Cathrin Waindok, Theresa Pesch, Mark Pogson, Kyle Ford, Cristina Parola, Sai T Reddy

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. 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
1.0field-weighted citation impact, top 25% 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, 21 citations in OpenAlex.

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  9. A small molecule redistributes iron in ferroportin-deficient mice and patient-derived primary macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2022
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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

7 authors at 1 institution in 1 country.

William KeltonDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Ann Cathrin WaindokDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Theresa PeschDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Mark PogsonDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Kyle FordDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Cristina ParolaDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Sai T ReddyDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
ETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The development of programmable nucleases has enabled the application of new genome engineering strategies for cellular immunotherapy. While targeted nucleases have mostly been used to knock-out or knock-in genes in immune cells, the scarless exchange of entire immunogenomic alleles would be of great interest. In particular, reprogramming the polymorphic MHC locus could enable the creation of matched donors for allogeneic cellular transplantation. Here we show a proof-of-concept for reprogramming MHC-specificity by performing CRISPR-Cas9-assisted cassette exchange. Using murine antigen presenting cell lines (RAW264.7 macrophages), we demonstrate that the generation of Cas9-induced double-stranded breaks flanking the native MHC-I H2-Kd locus led to exchange of an orthogonal H2-Kb allele. MHC surface expression allowed for easy selection of reprogrammed cells by flow cytometry, thus obviating the need for additional selection markers. MHC-reprogrammed cells were fully functional as they could present H2-Kd-restricted peptide and activate cognate T cells. Finally, we investigated the role of various donor template formats on exchange efficiency, discovering that templates that underwent in situ linearization resulted in the highest MHC-reprogramming efficiency. These findings highlight a potential new approach for the correcting of MHC mismatches in cellular transplantation.

Indexed as

CRISPR-Cas SystemsAnimalsCell LineCell Line, TumorDNA Breaks, Double-StrandedFibroblastsFlow CytometryH-2 AntigensMacrophagesMajor Histocompatibility ComplexMiceMice, Inbred BALB CH-2 Antigens

Identifiers

PMID28374766
PMCPMC5379551
OpenAlexW2604715983

What OpenQuestion holds

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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.