Nature-inspired dynamic gene-loaded nanoassemblies for the treatment of brain diseases.

Abstract Gene therapy has great potential to treat brain diseases. However, genetic drugs need to overcome a cascade of barriers for their full potential. The conventional delivery systems often struggle to meet expectations. Natural biological particles that are highly optimized for specific functions in body, can inspire optimization of dynamic gene-loaded nanoassemblies (DGN). The DGN refer to gene loaded nanoassemblies whose functions and structures are changeable in response to the biological microenvironments or can dynamically interact with tissues or cells. The nature-inspired DGN can meet the needs in brain diseases treatment, including i) N on-elimination in blood (N), ii) A cross the blood-brain barrier (A), iii) T argeting cells (T), iv) Efficient u ptake (U), v) Controllable r elease (R), vi) E yeable (E)-abbreviated as the “NATURE”. In this Review, from nature to “NATURE”, we mainly summarize the specific application of nature-inspired DGN in the “NATURE” cascade process. Furthermore, the Review provides an outlook for this field.