Nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level...Nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level.Ideally,this kind of treatment modality will not lead to an unwanted immune response.Compared with traditional treatment methods,nucleic acid therapeutics can achieve prolonged and stable curative effects.As an emerging treatment method,nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions,including infectious diseases,cancer,immune-related diseases,and monogenetic diseases.To date,a large number of clinical trials have been conducted,and more than 30 nucleic acid drugs have been approved,highlighting the strong potential of this approach in clinical practice.Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately.However,some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver.Therefore,biosafety assessment of delivery systems before their application in clinical settings is critical.In this review,we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies,with particular focus on the carriers themselves,drug administration method,and overall treatment of the disease.展开更多
Short DNA represents an important class of bioma-cromolecules that arewidely applied in gene therapy,editing,and modulation.However,the development of simple and reliable methods for their intracellular delivery remai...Short DNA represents an important class of bioma-cromolecules that arewidely applied in gene therapy,editing,and modulation.However,the development of simple and reliable methods for their intracellular delivery remains a challenge.Herein,we describe that seven water-soluble,homogeneous supramole-cular organic frameworks(SOFs)with a well-defined pore size and high stability in water that can accom-plish in situ inclusion of single-stranded(ss)and double-stranded(ds)DNA(21,23,and 58 nt)and effective intracellular delivery(including two non-cancerous and six cancerous cell lines).展开更多
基金support from the National Natural Science Foundation of China(Nos.22161132008 and 81822024)the Natural Science Foundation of Shanghai,China(Nos.19520714100 and 19ZR1475800)the Project of Shanghai Jiao Tong University(2019QYA03 and YG2017ZD07).
文摘Nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level.Ideally,this kind of treatment modality will not lead to an unwanted immune response.Compared with traditional treatment methods,nucleic acid therapeutics can achieve prolonged and stable curative effects.As an emerging treatment method,nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions,including infectious diseases,cancer,immune-related diseases,and monogenetic diseases.To date,a large number of clinical trials have been conducted,and more than 30 nucleic acid drugs have been approved,highlighting the strong potential of this approach in clinical practice.Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately.However,some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver.Therefore,biosafety assessment of delivery systems before their application in clinical settings is critical.In this review,we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies,with particular focus on the carriers themselves,drug administration method,and overall treatment of the disease.
基金We thank the National Natural Science Foundation of China(Nos.21432004 and 21529201)for financial sup-port,Shanghai Synchrotron Radiation Facility for provid-ing BL16B1 and BL14B1 beamlines for collecting the synchrotron X-ray-scattering and diffraction data,and the SIBYLS Beamline 12.3.1 of the Advanced Light Source(ALS),Lawrence Berkeley National Laboratory,for collecting solution-phase,synchrotron small-angle X-ray-scattering data.
文摘Short DNA represents an important class of bioma-cromolecules that arewidely applied in gene therapy,editing,and modulation.However,the development of simple and reliable methods for their intracellular delivery remains a challenge.Herein,we describe that seven water-soluble,homogeneous supramole-cular organic frameworks(SOFs)with a well-defined pore size and high stability in water that can accom-plish in situ inclusion of single-stranded(ss)and double-stranded(ds)DNA(21,23,and 58 nt)and effective intracellular delivery(including two non-cancerous and six cancerous cell lines).
