Evidence map›Paper›PMID 35021064›Full record

ArticleCell2022

Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins.

Samagya Banskota, Aditya Raguram, Susie Suh, Samuel W Du, Jessie R Davis, Elliot H Choi, Xiao Wang, Sarah C Nielsen, Gregory A Newby, Peyton B Randolph and 4 more

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

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 417 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
417citing papers in PubMed, 1 pooled it
100.2field-weighted citation impact, top 1% 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

417 citing papers in PubMed, 1 synthesis or guideline pooled it, 579 citations in OpenAlex.

  1. CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Pooled it
  2. Virus-Like Particles as a Nonviral CRISPR/Cas Editing Delivery Tool.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  3. Overview of Delivery Methods for Gene Editing.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
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  8. Review
  9. Article
  10. Article
  11. Article
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  13. Chemically modified CRISPR enzymes for multi-organ genome editingbioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Article
  16. Review
  17. Review
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  20. Article

357 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Samagya BanskotaMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
Aditya RaguramMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
Susie SuhGavin Herbert Eye Institute, Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Samuel W DuGavin Herbert Eye Institute, Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA; Department of Physiology and Biophysics, University of California, Irvine, CA, USA.
Jessie R DavisMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
Elliot H ChoiGavin Herbert Eye Institute, Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Xiao WangCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Sarah C NielsenDepartment of Pediatrics, Division of Blood and Marrow Transplant and Cellular Therapy, University of Minnesota, Minneapolis, MN, USA.
Gregory A NewbyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
Peyton B RandolphMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
Mark J OsbornDepartment of Pediatrics, Division of Blood and Marrow Transplant and Cellular Therapy, University of Minnesota, Minneapolis, MN, USA.
Kiran MusunuruCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Krzysztof PalczewskiGavin Herbert Eye Institute, Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA; Department of Physiology and Biophysics, University of California, Irvine, CA, USA; Department of Chemistry, University of California, Irvine, CA, USA; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA. Electronic address: drliu@fas.harvard.edu.
Broad Institute · USUniversity of California, Irvine · USCardiovascular Institute of the South · USUniversity of Minnesota · US

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI John E. Wagner · 1995 to 2026
$48.2M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
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
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008620 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GOLDIN, ALAN L · 1999 to 2023
$8.1M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome EditingR35HL145203 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUSUNURU, KIRAN · 2019 to 2025
$5.7M
Principles of Scientific Citizenship: Ethics, Communication, and Leadership for ScientistsT32GM095450 · NIGMS · HARVARD UNIVERSITY · PI WALKER, SUZANNE · 2011 to 2020
$3.5M
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
Cole Eye Institute Vision Science Training ProgramT32EY024236 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI ANAND-APTE, BELA · 2015 to 2025
$1.0M
microRNA-204 and microRNA-211 regulation of RPE phagocytosisF30EY033642 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Samuel Wang Du · 2022 to 2026
$241k
NCI NIH HHS P01 CA065493NEI NIH HHS F30 EY029136NEI NIH HHS F30 EY033642NEI NIH HHS R01 EY009339NEI NIH HHS T32 EY024236NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS R35 HL145203NIAID NIH HHS U01 AI142756NIAID NIH HHS UG3 AI150551NIGMS NIH HHS R35 GM118062NIGMS NIH HHS T32 GM007250NIGMS NIH HHS T32 GM008620NIGMS NIH HHS T32 GM095450
6 · The paper itself

Abstract

Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.

Indexed as

Drug Delivery SystemsGenetic EngineeringAnimalsBase SequenceBlindnessBrainDisease Models, AnimalDNAFibroblastsGene EditingHEK293 CellsHumansLiverMiceMice, Inbred C57BLProprotein Convertase 9DNAProprotein Convertase 9Proteinsbase editinggenome editingin vivo deliveryribonucleoproteinstherapeutic gene editingvirus-like particles

Identifiers

PMID35021064
PMCPMC8809250
OpenAlexW4206390074

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.