期刊
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
卷 17, 期 -, 页码 1828-1848出版社
BEILSTEIN-INSTITUT
DOI: 10.3762/bjoc.17.125
关键词
antisense oligonucleotides; backbone modifications; cations; nucleobase modifications; sugar modifications
资金
- VILLUM FONDEN [VKR18333]
ASOs have the potential to inhibit gene expression, but face challenges in delivery and toxicity profiles. By functionalizing ASOs with cationic amine groups, their properties can be improved. This review emphasizes the impact of common cationic amine group modifications on ASOs, and concludes with important knowledge and future design considerations.
Antisense oligonucleotides (ASOs) have the ability of binding to endogenous nucleic acid targets, thereby inhibiting the gene expression. Although ASOs have great potential in the treatment of many diseases, the search for favorable toxicity profiles and distribution has been challenging and consequently impeded the widespread use of ASOs as conventional medicine. One strategy that has been employed to optimize the delivery profile of ASOs, is the functionalization of ASOs with cationic amine groups, either by direct conjugation onto the sugar, nucleobase or internucleotide linkage. The introduction of these positively charged groups has improved properties like nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has been separated into three sections, nucleobase, sugar and backbone modifications, highlighting what impact the cationic amine groups have on the ONs/ASOs physio-chemical and biological properties. Finally, a concluding section has been added, summarizing the important knowledge from the three chapters, and examining the future design for ASOs.
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