Evidence map›Paper›PMID 39091760›Full record

ArticlebioRxiv : the preprint server for biology2024

Mechanism-guided engineering of a minimal biological particle for genome editing.

Wayne Ngo, Julia T Peukes, Alisha Baldwin, Zhiwei Wayne Xue, Sidney Hwang, Robert R Stickels, Zhi Lin, Ansuman T Satpathy, James A Wells, Randy Schekman and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Wayne NgoInnovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA.ORCID 0000-0002-5755-2303
Julia T PeukesCalifornia Institute for Quantitative Biosciences, University of California, Berkeley; Berkeley, CA, USA.ORCID 0000-0001-8560-7407
Alisha BaldwinInnovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA.ORCID 0009-0004-8484-2092
Zhiwei Wayne XueInnovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA.
Sidney HwangDepartment of Pathology, Stanford University; Stanford, CA, USA.
Robert R StickelsDepartment of Pathology, Stanford University; Stanford, CA, USA.ORCID 0000-0003-4326-4084
Zhi LinDepartment of Pharmaceutical Chemistry, University of California, San Francisco; San Francisco, CA, USA.ORCID 0000-0001-6662-7330
Ansuman T SatpathyDepartment of Pathology, Stanford University; Stanford, CA, USA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California, San Francisco; San Francisco, CA, USA.
Randy SchekmanDepartment of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA, USA.
Eva NogalesCalifornia Institute for Quantitative Biosciences, University of California, Berkeley; Berkeley, CA, USA.
Jennifer A DoudnaInnovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA.ORCID 0000-0001-9161-999X

Funding

New protein engineering-based tools and technologies for characterizing cell surface proteolysis in cancer cells for novel neo-epitope biomarkers and drug targetsR01CA248323 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES A WELLS · 2020 to 2026
$2.6M
Targeted Delivery of Cas9 to Lung Epithelial Cells using Enveloped Delivery VehiclesR21HL173710 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI DOUDNA, JENNIFER A · 2024 to 2025
$520k
NCI NIH HHS R01 CA248323NHLBI NIH HHS R21 HL173710
6 · The paper itself

Abstract

The widespread application of genome editing to treat or even cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped Delivery Vehicles (EDVs) are engineered virally-derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication components in EDVs has obscured the underlying delivery mechanism and precluded particle optimization. Here we show that Cas9 RNP nuclear delivery is independent of the native lentiviral capsid structure. Instead, EDV-mediated genome editing activity corresponds directly to the number of nuclear localization sequences on the Cas9 enzyme. EDV structural analysis using cryo-electron tomography and small molecule inhibitors guided the removal of ~80% of viral residues, creating a minimal EDV (miniEDV) that retains full RNP delivery capability. MiniEDVs are 25% smaller yet package equivalent amounts of Cas9 RNPs relative to the original EDVs, and demonstrated increased editing in cell lines and therapeutically-relevant primary human T cells. These results show that virally-derived particles can be streamlined to create efficacious genome editing delivery vehicles that could simplify production and manufacturing.

Identifiers

PMID39091760
PMCPMC11291128

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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.