Published: Feb. 11, 2020


Antisense oligonucleotides are synthetic DNAs that bind to RNA and alter or reduce the biological activity of the target RNA. Studies performed in recent years have demonstrated that an antisense strategy can be utilized to address various issues in fundamental biomedical research and have additionally shown that this approach can be used to create novel therapeutic drugs.


CU Boulder researchers in Dr. Marvin Caruthers' lab have synthesized a novel DNA analogue using modified phosphoramidite chemistry. The resulting phosphoramidimidate DNA is positively charged, nuclease resistant, forms duplexes with complementary unmodified oligonucleotides and is stable to neutral and basic conditions. Additionally, a very unique attribute of this analogue is that it is tolerated in the RNase H1 cleavage domain. Consequently, this phosphoramidimidate antisense oligonucleotide is expected to be more stable toward cellular nucleases and consequently have significantly longer half-life when used as therapeutic drugs. This analogue has been successfully and efficiently transfected, via passive transfection, into the cytoplasm of HeLa cells.

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