The overall objective of B-SMART is: 1. to design modular nanoparticles, 2. to manufacture them via a quality-by-design protocol, 3. to achieve delivery of therapeutic RNAs to the brain and treat neurodegenerative diseases. I. To design modular nanoparticles consisting of o an active RNA payloado established (lipid-based), emerging (trigger-responsive polymer-based) or exploratory (extracellular vesicle-based) nanoparticleso a targeting ligand consisting of the variable domain of heavy chain only antibodies (also known as VHHs or nanobodies), which are coupled to the carrier platformII. To manufacture the modular nanoparticles using a microfluidic assembly system that will ensure quality-by-design: uniform nanoparticles across research sites and excellent control over the physico-chemical parameters. III. To test pre-clinical activity of formulations with promising in vitro activity with good cell/blood compatibility and to select the best RNA-formulation for clinical translation to treat neurodegenerative diseases.Pre-clinical efficacy is tested aftero local injection o nasal administrationo systemic administrationThe neurodegenerative diseases carry a high burden for patients since they are without exception progressive. But they also carry a substantial socio-economic burden with estimated costs of 130 billion euro. per year (2008).IV. The technical work in B-SMART will be supported by project management. It ensures that the project is coordinated in a clear, unambiguous and mutually acceptable manner and that the project achieves its objectives, within the given financial and time constraints.in B-SMART we expect to arrive at a scale-able nanoparticle formulation with uniform characteristics that shows strong pre-clinical evidence of therapeutic efficacy and is ready for clinical translation.