Journal of the American Chemical Society
Journal of the American Chemical Society
5 years ago

Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)–DNA Conjugates

Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)–DNA Conjugates
Xuyu Tan, Xueyan Cao, Xueguang Lu, Ke Zhang, Hao Lu, Dali Wang, Fei Jia
PEGylation of an oligonucleotide using a brush polymer can improve its biopharmaceutical characteristics, including enzymatic stability and biodistribution. Herein, we quantitatively explore the nuclease accessibility of the nucleic acid as a function of “depth” toward the backbone of the brush polymer. It is found that protein accessibility decreases as the nucleotide is located closer to the backbone. Thus, by moving the conjugation point from the terminus of the nucleic acid strand to an internal position, much smaller brushes can be used to achieve the same level of steric shielding. This finding also makes it possible to assess antisense gene regulation efficiency of these brush–DNA conjugates as a function of their nuclease stability.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b05064

DOI: 10.1021/jacs.7b05064

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