Evidence map›Paper›PMID 36077152›Full record

ArticleInternational journal of molecular sciences2022

A Pan-RNase Inhibitor Enabling CRISPR-mRNA Platforms for Engineering of Primary Human Monocytes.

Kanut Laoharawee, Matthew J Johnson, Walker S Lahr, Christopher J Sipe, Evan Kleinboehl, Joseph J Peterson, Cara-Lin Lonetree, Jason B Bell, Nicholas J Slipek, Andrew T Crane and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 44% 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

6 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
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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

12 authors at 1 institution in 1 country.

Kanut LaoharaweeDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0001-8216-2131
Matthew J JohnsonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Walker S LahrDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Christopher J SipeDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Evan KleinboehlDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Joseph J PetersonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Cara-Lin LonetreeDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-2760-8572
Jason B BellDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Nicholas J SlipekDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0003-2664-6507
Andrew T CraneDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0003-3452-2766
Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-3950-8747
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
University of Minnesota · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Monocytes and their downstream effectors are critical components of the innate immune system. Monocytes are equipped with chemokine receptors, allowing them to migrate to various tissues, where they can differentiate into macrophage and dendritic cell subsets and participate in tissue homeostasis, infection, autoimmune disease, and cancer. Enabling genome engineering in monocytes and their effector cells will facilitate a myriad of applications for basic and translational research. Here, we demonstrate that CRISPR-Cas9 RNPs can be used for efficient gene knockout in primary human monocytes. In addition, we demonstrate that intracellular RNases are likely responsible for poor and heterogenous mRNA expression as incorporation of pan-RNase inhibitor allows efficient genome engineering following mRNA-based delivery of Cas9 and base editor enzymes. Moreover, we demonstrate that CRISPR-Cas9 combined with an rAAV vector DNA donor template mediates site-specific insertion and expression of a transgene in primary human monocytes. Finally, we demonstrate that SIRPa knock-out monocyte-derived macrophages have enhanced activity against cancer cells, highlighting the potential for application in cellular immunotherapies.

Indexed as

CRISPR-Cas SystemsRibonucleasesEndoribonucleasesGene EditingGene Knockout TechniquesGenetic EngineeringHumansMonocytesRNA, MessengerEndoribonucleasesRibonucleasesRNA, Messengerbase editorCRISPR-Cas9genome engineeringpan-RNase inhibitorprimary human monocytes

Identifiers

PMID36077152
PMCPMC9456164
OpenAlexW4293426408

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.