Evidence map›Paper›PMID 37678882›Full record

ArticleNucleic acids research2023

Engineered lentivirus-derived nanoparticles (LVNPs) for delivery of CRISPR/Cas ribonucleoprotein complexes supporting base editing, prime editing and in vivo gene modification.

Jakob Haldrup, Sofie Andersen, Alexander Rafael LaVilla Labial, Jonas Holst Wolff, Frederik Plum Frandsen, Thomas Wisbech Skov, Anne Bruun Rovsing, Ian Nielsen, Thomas Stax Jakobsen, Anne Louise Askou and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
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  8. A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  9. Article
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  13. Article
  14. Engineering Microbial Particles for Next-Generation Biomedical Platforms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  15. Article
  16. Review
  17. Article
  18. Advances in Engineered Virus-Like Particles for Genome Editing and Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  19. Nature Inspired Delivery Vehicles for CRISPR-Based Genome Editing.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  20. 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

14 authors at 1 institution in 1 country.

Jakob HaldrupDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Sofie AndersenDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Alexander Rafael LaVilla LabialDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Jonas Holst WolffDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.ORCID 0000-0001-5690-7603
Frederik Plum FrandsenDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Thomas Wisbech SkovDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Anne Bruun RovsingDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.ORCID 0000-0002-0510-180X
Ian NielsenDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Thomas Stax JakobsenDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Anne Louise AskouDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Martin K ThomsenDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Thomas J CorydonDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Emil Aagaard ThomsenDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.ORCID 0000-0002-2685-7745
Jacob Giehm MikkelsenDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.ORCID 0000-0002-1322-3209
Aarhus University · DK

Funding

Innovation Fund 8056-00010ALundbeck Foundation R324-2019-1832Synoptik FoundationVelux Foundation 38189
6 · The paper itself

Abstract

Implementation of therapeutic in vivo gene editing using CRISPR/Cas relies on potent delivery of gene editing tools. Administration of ribonucleoprotein (RNP) complexes consisting of Cas protein and single guide RNA (sgRNA) offers short-lived editing activity and safety advantages over conventional viral and non-viral gene and RNA delivery approaches. By engineering lentivirus-derived nanoparticles (LVNPs) to facilitate RNP delivery, we demonstrate effective administration of SpCas9 as well as SpCas9-derived base and prime editors (BE/PE) leading to gene editing in recipient cells. Unique Gag/GagPol protein fusion strategies facilitate RNP packaging in LVNPs, and refinement of LVNP stoichiometry supports optimized LVNP yield and incorporation of therapeutic payload. We demonstrate near instantaneous target DNA cleavage and complete RNP turnover within 4 days. As a result, LVNPs provide high on-target DNA cleavage and lower levels of off-target cleavage activity compared to standard RNP nucleofection in cultured cells. LVNPs accommodate BE/sgRNA and PE/epegRNA RNPs leading to base editing with reduced bystander editing and prime editing without detectable indel formation. Notably, in the mouse eye, we provide the first proof-of-concept for LVNP-directed in vivo gene disruption. Our findings establish LVNPs as promising vehicles for delivery of RNPs facilitating donor-free base and prime editing without formation of double-stranded DNA breaks.

Indexed as

CRISPR-Cas SystemsGene EditingLentivirusNanoparticlesRibonucleoproteinsAnimalsCRISPR-Associated Protein 9HEK293 CellsHumansMiceRNA, Guide, CRISPR-Cas SystemsCRISPR-Associated Protein 9RibonucleoproteinsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37678882
PMCPMC10570023
OpenAlexW4386528923

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.