• Virus-like particles
• RNAi
• synaptic plasticity
• RNA localization
• micro-RNAs

In the central nervous system, RNA localization plays a pivotal role since the local translation of mRNAs at dendrites can be triggered by synaptic activation and is thought to induce plastic changes that occur at synapses triggered by learning and memory. There are multiple advantages in mRNA localization as a key regulatory mechanism to fine-tune gene expression. First, the localization of mRNA, rather than its corresponding protein, targets the protein directly to the correct intracellular compartment while preventing its expression elsewhere. Second, it provides a synapse with the unique opportunity to spa-tially restrict gene expression with high temporal resolution. Third, it is more economic to reuse a giv-en transcript several times for multiple rounds of translation instead of transporting each protein or transcript individually to a distinct synapse.
In dendritic spines, the protein synthesis and degradation is modulated by several mechanisms includ-ing RNA interference. Indeed also some miRNAs accumulated at the dendrites in synaptic activity de-pendent manner and correlates with dendritic growth.
Despite several evidence that different mRNAs and miRNAs accumulate depending on synaptic activa-tion, technical limits prevented the uncoupling and identification of dendritic RNA pools from all other cellular RNAs. Up to now the only method is the purification of synaptosomes, that are constituted by both post and pre-synaptic material.
To overcome this limitation, I developed engineered HIV-based Virus–Like Particles (VLPs) to specifical-ly incorporate dendritic RNA species. In particular, I induced the formation of VLPs in dendrites by add-ing a specific localization signal to Gag protein. Moreover, In order to enrich VLPs of miRNAs, I fused a miRNAs binding domains to Gag.
Preliminary results indicated that engineered VLPs form with the expected size and shape and target the dendrites in neuroblastoma cells and in primary hippocampal neurons.