Anionic liposomes for small interfering ribonucleic acid (siRNA) delivery to primary neuronal cells: Evaluation of alpha-synuclein knockdown efficacy
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Alpha-synuclein (α-syn) deposition in Lewy bodies (LB) is one of the main neuropathological hallmarks of Parkinson’s disease (PD). LB accumulation is considered a causative factor of PD, which suggests that strategies aimed at reducing α-syn levels could be relevant for its treatment. In the present study, we developed novel nanocarriers suitable for systemic delivery of small interfering ribonucleic acid (siRNA) that were specifically designed to reduce neuronal α-syn by RNA interference. Anionic liposomes loaded with an siRNA–protamine complex for α-syn gene silencing and decorated with a rabies virus glycoprotein (RVG)-derived peptide as a targeting agent were prepared. The nanoparticles were characterized for their ability to load, protect, and deliver the functional siRNA to mouse primary hippocampal and cortical neurons as well as their efficiency to induce gene silencing in these cells. Moreover, the nanocarriers were evaluated for their stability in serum. The RVG-decorated liposomes displayed suitable characteristics for future in vivo applications and successfully induced α-syn gene silencing in primary neurons without altering cell viability. Collectively, our results indicate that RVG-decorated liposomes may be an ideal tool for further studies aimed at achieving efficient in vivo α-syn gene silencing in mouse models of PD.
Keywordsrabies virus glycoprotein (RVG) peptide liposomes small interfering ribonucleic acid (siRNA) alpha-synuclein primary neuronal cells Parkinson’s disease
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The authors gratefully acknowledge Micaela Morelli for supporting the establishment of the collaboration between the groups participating to this study. M. S. thanks Angela Corona for fruitful discussions about the design and implementation of the project. A. B. is grateful to “Ambrosini Arredamenti SNC” for funding support within the project “Molecular Mechanisms, associated with Neurodegenerative Diseases” and the Italian Ministry of Education, University and Scientific Research—University of Brescia Ex 60% Research Funds.
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