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dc.contributor.authorKhvorova, Anastasia
dc.contributor.authorWatts, Jonathan K
dc.date2022-08-11T08:09:47.000
dc.date.accessioned2022-08-23T16:43:36Z
dc.date.available2022-08-23T16:43:36Z
dc.date.issued2017-03-01
dc.date.submitted2017-09-15
dc.identifier.citationNat Biotechnol. 2017 Mar;35(3):238-248. doi: 10.1038/nbt.3765. Epub 2017 Feb 27. <a href="https://doi.org/10.1038/nbt.3765">Link to article on publisher's site</a>
dc.identifier.issn1087-0156 (Linking)
dc.identifier.doi10.1038/nbt.3765
dc.identifier.pmid28244990
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40328
dc.description.abstractAfter nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base sequence. Thus, as oligonucleotides with a particular chemical design show appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue. To achieve clinical productivity, the chemical architecture of the oligonucleotide needs to be optimized with a combination of sugar, backbone, nucleobase, and 3'- and 5'-terminal modifications. A portfolio of chemistries can be used to confer drug-like properties onto the oligonucleotide as a whole, with minor chemical changes often translating into major improvements in clinical efficacy. One outstanding challenge in oligonucleotide chemical development is the optimization of chemical architectures to ensure long-term safety. There are multiple designs that enable effective targeting of the liver, but a second challenge is to develop architectures that enable robust clinical efficacy in additional tissues.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=28244990&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517098/
dc.subjectBiochemistry
dc.subjectBiotechnology
dc.subjectChemicals and Drugs
dc.subjectMedicinal Chemistry and Pharmaceutics
dc.subjectTherapeutics
dc.titleThe chemical evolution of oligonucleotide therapies of clinical utility
dc.typeJournal Article
dc.source.journaltitleNature biotechnology
dc.source.volume35
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3129
dc.identifier.contextkey10750073
html.description.abstract<p>After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base sequence. Thus, as oligonucleotides with a particular chemical design show appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue. To achieve clinical productivity, the chemical architecture of the oligonucleotide needs to be optimized with a combination of sugar, backbone, nucleobase, and 3'- and 5'-terminal modifications. A portfolio of chemistries can be used to confer drug-like properties onto the oligonucleotide as a whole, with minor chemical changes often translating into major improvements in clinical efficacy. One outstanding challenge in oligonucleotide chemical development is the optimization of chemical architectures to ensure long-term safety. There are multiple designs that enable effective targeting of the liver, but a second challenge is to develop architectures that enable robust clinical efficacy in additional tissues.</p>
dc.identifier.submissionpathoapubs/3129
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentRNA Therapeutics Institute
dc.source.pages238-248


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