Evidence map›Paper›PMID 41945434›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Humanized extracellular vesicles for efficient RNA delivery.

Xiang Ma, Sophia R Zhao, Constance L Cepko

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Xiang MaDepartment of Genetics, Harvard Medical School, Boston, MA 02115.
Sophia R ZhaoDepartment of Genetics, Harvard Medical School, Boston, MA 02115.
Constance L CepkoDepartment of Genetics, Harvard Medical School, Boston, MA 02115.ORCID 0000-0002-9945-6387

Funding

Blavatnik Biomedical Accelerator NAHHMI (HHMI) NA
6 · The paper itself

Abstract

Engineered extracellular vesicles (EVs) are a class of nonviral delivery vectors for RNA-based vaccines and gene therapies. A specialized form of engineered EVs, known as enveloped protein nanocages (EPNs), has been developed to enhance cargo loading and delivery. When EPNs are equipped with a viral fusogen, such as vesicular stomatitis virus glycoprotein (VSV-G), they have been shown to deliver proteins or RNA efficiently into recipient cells. Comparisons across different EPN types and optimization of their different features have been difficult, as assays for their activity have not been reported for single, active units. As we were interested in optimizing EVs, we first developed a biological titration assay inspired by the methods used for infectious viral particles. With this assay, we optimized EVs using a modular platform, creating EVs composed predominantly of human-derived protein components. This system achieved efficient RNA delivery, with functional titers comparable to those of lentiviral vectors. The optimized chimeric proteins comprising the EV particles integrate domains from human epsin 1, human citramalyl-CoA lyase beta-like protein (CLYBL), and human CEP55. The constructs also include a short 21-amino-acid peptide from a nonhuman source for RNA packaging, resulting in an EV-based RNA delivery system with reduced immunogenicity compared with EPNs and retroviral virus-like particles (VLPs).

Indexed as

Extracellular VesiclesGene Transfer TechniquesRNAGenetic VectorsHEK293 CellsHumansRNAcitramalyl-CoA lyase beta-like protein (CLYBL)EABRenveloped protein nanocages (EPNs)Epsin N-terminal homology (ENTH)functional titers

Identifiers

PMID41945434
PMCPMC13079979

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.