Research Progress of siRNA Nano-delivery System

Small interfering RNA(siRNA)is the initiator of RNA interference,which stimulates the silencing ofcomplementary target mRNA.It is of great significance for gene regulation and disease treatment.It is used inviral infections,cancers,family genetic diseases and autoimmune diseases.As a new type of drug,siRNA isgradually being valued by researchers due to its high efficiency,strong specificity,and easy detection oftherapeutic effects.siRNA used as a drug alone or co-delivered with anti-tumor drugs such as chemotherapy forcancer treatment shows greater application potential than traditional drugs.siRNA drugs have the advantages ofdesignable targeting,convenient synthesis,instantaneous silencing,and strong target specificity.However,theirdelivery also faces obstacles that they are easily degraded in the blood circulation,cleared by the kidney,anddifficult to break through the vascular endothelium/cell membrane/lysosome.Therefore,designing suitablenanocarriers to help siRNA successfully deliver into cells and play a role is an important goal for the developmentof siRNA drugs,and the amout of research in this area is also increasing year by year.The precise design of thenanocarrier material type,size,structure,surface modification,etc.are important factors for the successfuldelivery of siRNA drugs.At present,the design of siRNA drug nanocarriers mainly includes4strategies:loadingsiRNA drugs on the surface of nanocarriers,co-assembly of siRNA drugs and nanocarriers,nanocarriersencapsulating siRNA drugs,and siRNA self-assembly.At this stage,the use of nanocarriers to achieve siRNAdrug delivery has made great progress.With the in-depth research and application development,the precisecontrolled preparation,precise targeted delivery and multifunctionalization of siRNA drug nanocarriers haveachieved good results.However,there are still some problems that need to be overcome by researchers.Forexample,when siRNA drugs are used in the clinic,there are still problems such as inaccurate structure design oftargeted drugs,serious off-target effects,difficulty in achieving endosome escape,and difficulties in large-scalepreparation of nanocarriers.Because of this,only3siRNA drugs have been approved for marketing,namelyOnpattro(Patisiran),Givlaari(Givosiran)and Oxlumo(Lumasiran)developed by Alnylam Pharmaceuticals.Howto prepare siRNA drugs on a large scale is a major problem facing the clinical application of siRNA drugs,and itwill become a research hotspot.At the same time,with the development of computer technology,combined withartificial intelligence,machine learning and other technologies,drug design with the aid of big data analysis isbecoming a new research and development trend.Intelligent design and precise regulation of siRNAnanomedicine,and the design of multifunctional siRNA nanomedicine that integrates targeting,tracing,and co-delivery with other drugs to achieve synergy is also one of the future development directions of siRNAnano medicine