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Background <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月27日

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  • Marianna Mignanelli,
  • Giacomo Siano,
  • Vincenzo Iannone,
  • Arianna Scarlatti,
  • Emanuele Orsini,
  • Ludovico Maggi,
  • Milena Rizzo,
  • Maria Claudia Caiazza,
  • Richard Wade-Martins,
  • Alessandra Salvetti,
  • Greta Ghiloni,
  • Federico Cremisi,
  • Valentina Casieri,
  • Lorenzo Fruzzetti,
  • Elena Novelli,
  • Alì Ataman,
  • Antonino Cattaneo,
  • Cristina Di Primio

摘要

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