Evidence map›Paper›PMID 40374955›Full record

ArticleNature biotechnology2026

Self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins.

Feyisayo Eweje, Vanessa Ibrahim, Aram Shajii, Michelle L Walsh, Kiran Ahmad, Assma Alrefai, Dominie Miyasato, Jessie R Davis, Hyunok Ham, Kaicheng Li and 5 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
–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

21 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  17. Advances in Inhaled Nanoparticle Drug Delivery for Pulmonary Disease Management.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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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

15 authors.

Feyisayo Eweje *Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7936-5384
Vanessa IbrahimDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0009-0354-6221
Aram ShajiiDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Michelle L WalshDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5563-5829
Kiran AhmadDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Assma AlrefaiDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0006-8904-7754
Dominie MiyasatoDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jessie R DavisDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Hyunok HamDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Kaicheng LiDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Michael RoehrlDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4892-1098
Carolyn A HallerDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
David R LiuDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Jiaxuan Chen *Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. jchen13@bidmc.harvard.edu.ORCID http://orcid.org/0000-0001-5801-9052
Elliot L ChaikofDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. echaikof@bidmc.harvard.edu.ORCID http://orcid.org/0000-0001-6184-4571

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
Delivery Technologies for In Vivo Genome EditingUG3AI150551 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT · 2019 to 2021
$2.3M
Delivery Technologies for In Vivo Genome EditingUH3AI150551 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT · 2022 to 2022
$1.4M
Self-Assembling Peptide Nanoparticles for in vivo Genome Editor Delivery to Hematopoietic Stem CellsF31HL167533 · NHLBI · HARVARD MEDICAL SCHOOL · PI Feyisayo Ronald Eweje · 2023 to 2026
$216k
NHLBI NIH HHS F31 HL167533NIAID NIH HHS UG3 AI150551NIAID NIH HHS UH3 AI150551NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) F31HL167533U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 5T32GM007753-42U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 5T32GM144273-02U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) UG3AI15055U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) UH3AI150551
6 · The paper itself

Abstract

Intracellular delivery of biomacromolecules is hampered by low efficiency and cytotoxicity. Here we report the development of elastin-based nanoparticles for therapeutic delivery (ENTER), a recombinant elastin-like polypeptide (ELP)-based delivery system for effective cytosolic delivery of biomacromolecules in vitro and in vivo. Through iterative design, we developed fourth-generation ELPs fused to cationic endosomal escape peptides (EEPs) that self-assemble into pH-responsive micellar nanoparticles and enable cytosolic entry of cargo following endocytic uptake. In silico screening of α-helical peptide libraries led to the discovery of an EEP (EEP13) with 48% improved protein delivery efficiency versus a benchmark peptide. Our lead ELP-EEP13 showed similar or superior performance compared to lipid-based transfection reagents in the delivery of mRNA-encoded, DNA-encoded and protein-form Cre recombinase and CRISPR gene editors as well as short interfering RNAs to multiple cell lines and primary cell types. Intranasal administration of ELP-EEP13 combined with Cre protein achieved efficient editing of lung epithelial cells in reporter mice.

Indexed as

CytosolDrug Delivery SystemsNanoparticlesNucleic AcidsProteinsAnimalsElastinHumansMicePeptidesElastinNucleic AcidsPeptidesProteins

Identifiers

PMID40374955
PMCPMC13170490

What OpenQuestion holds

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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.