Evidence map›Paper›PMID 39537813›Full record

ArticleNature biotechnology2025

Directed evolution of engineered virus-like particles with improved production and transduction efficiencies.

Aditya Raguram, Meirui An, Paul Z Chen, David R Liu

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
–field-weighted citation impact
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

49 citing papers in PubMed.

  1. Base Editing: Mechanisms and Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
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  3. Chemically modified CRISPR enzymes for multi-organ genome editingbioRxiv : the preprint server for biology · 2026
    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

4 authors.

Aditya RaguramMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA. araguram@wi.mit.edu.ORCID http://orcid.org/0000-0002-5749-7308
Meirui AnMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4006-8670
Paul Z ChenMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5261-1610
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID http://orcid.org/0000-0002-9943-7557

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
STRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Novel Gene Editing Approaches for HemoglobinopathiesR01HL136135 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HANS-PETER KIEM · 2017 to 2026
$7.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Delivery Technologies for In Vivo Genome EditingUG3AI150551 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT · 2019 to 2021
$2.3M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) Liu grantHoward Hughes Medical Institute (HHMI) Liu investigatorshipNEI NIH HHS R01 EY009339NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS R01 HL136135NIAID NIH HHS U01 AI142756NIAID NIH HHS UG3 AI150551NIDDK NIH HHS U54 DK106829NIGMS NIH HHS R35 GM118062U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY009339U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL136135U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) RM1HG009490U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U01AI142756U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) UG3AI150551U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM118062
6 · The paper itself

Abstract

Engineered virus-like particles (eVLPs) are promising vehicles for transient delivery of proteins and RNAs, including gene editing agents. We report a system for the laboratory evolution of eVLPs that enables the discovery of eVLP variants with improved properties. The system uses barcoded guide RNAs loaded within DNA-free eVLP-packaged cargos to uniquely label each eVLP variant in a library, enabling the identification of desired variants following selections for desired properties. We applied this system to mutate and select eVLP capsids with improved eVLP production properties or transduction efficiencies in human cells. By combining beneficial capsid mutations, we developed fifth-generation (v5) eVLPs, which exhibit a 2-4-fold increase in cultured mammalian cell delivery potency compared to previous-best v4 eVLPs. Analyses of v5 eVLPs suggest that these capsid mutations optimize packaging and delivery of desired ribonucleoprotein cargos rather than native viral genomes and substantially alter eVLP capsid structure. These findings suggest the potential of barcoded eVLP evolution to support the development of improved eVLPs.

Indexed as

Directed Molecular EvolutionTransduction, GeneticVirionCapsidCapsid ProteinsGene EditingHEK293 CellsHumansMutationCapsid Proteins

Identifiers

PMID39537813
PMCPMC12085157

What OpenQuestion holds

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Registered trials

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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.