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Journal article

Synthetic nanoparticles for cell-type specific, spatially resolved loading and export of MiRNAs in neural cells

Abstract:
Background: Brain development and plasticity depend on specific microRNA (miRNA) expression patterns across cell types and subcellular compartments. Nevertheless, comprehensive profiling of localized brain miRNAs is still limited by challenges in isolating individual cell types or compartments and in detection sensitivity. Results: To overcome these limitations, we advanced HIV-1 Gag’s ability to bind host miRNAs within Virus-like Particles to develop Synthetic Nano-Particles for Precise endogenous miRNA loading and export (SNaP). Our data establish SNaP’s modularity and portability to clinically relevant neural cells, with particle yields matching benchmark packaging cells. The integration of SNaP with a cell-specific promoter enabled lineage-restricted miRNA export, while incorporating a dendritic localization signal improved the specificity of post-synaptic miRNA recovery over traditional synaptosomes. Additional engineering with a miRNA-binding module synergistically increased synaptic miRNA packaging in a sequence-independent manner. Conclusion: Collectively, this work positions SNaP as a technological advancement supporting the high-resolution, spatially resolved profiling of miRNAs, adaptable to diverse polarized or heterogeneous culture systems. Graphical Abstract: SNaP: Gag-based nanoparticles for spatially resolved neuronal miRNome profiling
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1186/s12951-026-04034-9

Authors


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Funder identifier:
10.13039/501100021856
Grant:
PRIN2022
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Funder identifier:
https://ror.org/029chgv08
Grant:
grant ref. 223202/Z/21/Z).
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Funder identifier:
10.13039/100009093
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Funder identifier:
https://ror.org/03aydme10
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Grant:
Next-Generation EU-MUR PNRR TUSCANY HEALTH Ecosystem (THE) (project no. ECS_00000017)


Publisher:
BioMed Central
Journal:
Journal of Nanobiotechnology More from this journal
Volume:
24
Issue:
1
Article number:
229
Publication date:
2026-01-27
Acceptance date:
2026-01-07
DOI:
EISSN:
1477-3155
ISSN:
1477-3155


Language:
English
Keywords:
Pubs id:
2365380
Local pid:
pubs:2365380
Source identifiers:
3843273
Deposit date:
2026-03-11
ARK identifier:
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