Non-natural nucleic acids for synthetic biology

Abstract

Genetic manipulation is an important facet of synthetic biology but can be complicated by undesired nuclease degradation. Incorporating non-natural nucleic acids into a gene could convey resistance to nucleases and promote expression. The compatibility of non-natural nucleosides with polymerases is reviewed with a focus on results from the past two years. Details are provided about how the different systems could be useful in synthetic biology.

Aptamers as imaging agents

“…The capping significantly increased resistance to exonuclease of a thrombin aptamer: 80% of the intact oligonucleotide was recovered after 2 h of treatment, whereas unmodified aptamer was 80% hydrolyzed in 30 min. Some of the modifications are compatible with the SELEX process, meaning that modified triphosphates are readily introduced by polymerases [13,[19][20][21]. From this point of view the incorporation of 2¢-fluororibonucleotide of pyrimidine residues is most frequently used for SELEX as it results in partly resistant molecules using a standard selection procedure.…”

Aptamers as Remarkable Diagnostic and Therapeutic Agents in Cancer Treatment

“…Both of them were screened from modified RNA library involving 2'F-Py nucleotides and to further increase the nucleases resistance, several of the natural purines were replaced by 2'O-Me purines [26,29]. Other modifications of the nucleotides on the ribose can be used to increase the stability of aptamers such as LNA (Locked Nucleic Acid) [30]. A TTA1 derivative was tailored using a small number of LNA, this aptamer exhibited an improved plasma stability together with higher tumour uptake compared to the non-modified TTA1 aptamer [31].…”

P-Stereodefined phosphorothioate analogs of glycol nucleic acids—synthesis and structural properties

“…The aqueous phase was concentrated under reduced pressure and the residue was chromatographed on a reverse phase silica gel column using water as eluent to yield 180 mg of 7 (75%); R f ¼ 0.55 (i-PrOH/conc. NH 4 …”

“…[4][5][6] In phosphorothioate analogs of DNA (PS-DNA) one of the non-bridging phosphate oxygen atoms is replaced with a sulfur atom (Fig. 1A).…”