Evidence map›Paper›PMID 36611948›Full record

ArticleCells2022

Delivery of CRISPR/Cas9 Plasmid DNA by Hyperbranched Polymeric Nanoparticles Enables Efficient Gene Editing.

Kemao Xiu, Laura Saunders, Luan Wen, Jinxue Ruan, Ruonan Dong, Jun Song, Dongshan Yang, Jifeng Zhang, Jie Xu, Y Eugene Chen and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
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

15 citing papers in PubMed, 17 citations in OpenAlex.

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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

11 authors at 1 institution in 1 country.

Kemao XiuDepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Laura SaundersMacromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA.
Luan WenCenter for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA.
Jinxue RuanCenter for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA.
Ruonan DongDepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Jun SongCenter for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-6128-6378
Dongshan YangCenter for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA.
Jifeng ZhangCenter for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA.
Jie XuCenter for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0001-9452-2878
Y Eugene ChenCenter for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA.
Peter X MaDepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-0191-9487
University of Michigan · US

Funding

Two-stage miRNA delivering scaffolds for patient-originated cells to regenerate blood vesselsR01HL136231 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2017 to 2020
$3.0M
A nanoparticle delivery system for CRISPR/Cas9 based therapeuticsR42TR001711 · NCATS · ATGC, INC. · PI KURODA, KENICHI · 2017 to 2019
$1.7M
NCATS NIH HHS R42 TR001711NHLBI NIH HHS R01 HL136231
6 · The paper itself

Abstract

Gene editing nucleases such as CRISPR/Cas9 have enabled efficient and precise gene editing in vitro and hold promise of eventually achieving in vivo gene editing based therapy. However, a major challenge for their use is the lack of a safe and effective virus-free system to deliver gene editing nuclease elements. Polymers are a promising class of delivery vehicle due to their higher safety compared to currently used viral vectors, but polymers suffer from lower transfection efficiency. Polymeric vectors have been used for small nucleotide delivery but have yet to be used successfully with plasmid DNA (pDNA), which is often several hundred times larger than small nucleotides, presenting an engineering challenge. To address this, we extended our previously reported hyperbranched polymer (HP) delivery system for pDNA delivery by synthesizing several variants of HPs: HP-800, HP-1.8K, HP-10K, HP-25K. We demonstrate that all HPs have low toxicity in various cultured cells, with HP-25K being the most efficient at packaging and delivering pDNA. Importantly, HP-25K mediated delivery of CRISPR/Cas9 pDNA resulted in higher gene-editing rates than all other HPs and Lipofectamine at several clinically significant loci in different cell types. Consistently, HP-25K also led to more robust base editing when delivering the CRISPR base editor "BE4-max" pDNA to cells compared with Lipofectamine. The present work demonstrates that HP nanoparticles represent a promising class of vehicle for the non-viral delivery of pDNA towards the clinical application of gene-editing therapy.

Indexed as

Gene EditingNanoparticlesCRISPR-Cas SystemsDNAGene Transfer TechniquesPlasmidsPolymersDNAPolymersCRISPR/Cas9gene deliverygene editingnanoparticlepDNAPEIpolyplex

Identifiers

PMID36611948
PMCPMC9818138
OpenAlexW4313473092

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.