Evidence map›Paper›PMID 41124242›Full record

ArticleScience advances2025

A multistep platform identifies spleen-tropic lipid nanoparticles for in vivo T cell-targeted delivery of gene-editing proteins.

Xiaoya Lu, Yining Zhu, Christine Wei, Leonardo Cheng, Kailei D Goodier, Jiayuan Kong, Xiangyu Gao, Di Yu, Xiang Liu, Yuanmuhuang Long and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  4. International journal of biological sciences · 2026
    Review
  5. Frontiers in immunology · 2026
    Review
  6. Targeted delivery platforms forFrontiers in pharmacology · 2026
    Review
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

14 authors.

Xiaoya LuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0009-1588-1772
Yining ZhuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-7178-0097
Christine WeiInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0005-0831-6813
Leonardo ChengInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-9214-8533
Kailei D GoodierInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0008-2397-2079
Jiayuan KongInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-5368-8940
Xiangyu GaoInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0006-0446-5413
Di YuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0003-5000-2100
Xiang LiuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0004-3069-5648
Yuanmuhuang LongInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0004-6740-7160
Jinghan LinInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0002-1475-1895
Jingyao MaInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Yunhe SuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Hai-Quan MaoInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-4262-9988

Funding

TR&D Project 3P41EB028239 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI Jordan Green, JONATHAN P SCHNECK · 2019 to 2026
$11.5M
Engineered Lipid Nanoparticles and Microgel Matrix to Program Th1/Th2 Immune ResponseR01CA293906 · NCI · JOHNS HOPKINS UNIVERSITY · PI Hai-Quan Mao · 2025 to 2026
$1.2M
NCI NIH HHS R01 CA293906NIBIB NIH HHS P41 EB028239
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) are a promising nonviral delivery system for gene-editing proteins, but optimal formulations remain underexplored. Unlike messenger RNA-based approaches, ribonucleoprotein delivery enables immediate genome editing without relying on endogenous translation. However, intracellular delivery remains a major challenge due to protein size, charge variability, and susceptibility to denaturation and degradation. Here, we present a multistep screening platform to optimize LNP formulations for gene-editing protein delivery, focusing on in vivo T cell targeting. Through in vitro screening of a composition library, we identified top-performing candidates. In vivo screening in Ai9 mice revealed a spleen-tropic LNP formulation that preferentially targets T cells, enabling efficient gene editing in vivo. Using this LNP formulation, we achieved targeted knockout of CCR5 and PD-1 in splenic T cells, supporting potential applications in HIV resistance and cancer immunotherapy. Furthermore, a machine learning-guided mechanistic study revealed key design principles for LNP-based protein delivery, highlighting unexplored opportunities for in vivo genome-editing therapies.

Indexed as

Gene EditingGene Transfer TechniquesLipidsNanoparticlesSpleenT-LymphocytesAnimalsCRISPR-Cas SystemsHumansLiposomesMiceReceptors, CCR5Lipid NanoparticlesLipidsLiposomesReceptors, CCR5

Identifiers

PMID41124242
PMCPMC12542943

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.