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May 03, 2012
 |  BC Innovations  |  Tools & Techniques

Evolution not revolution

An international team has engineered enzymes capable of replicating nucleic acid polymers that are made of non-natural nucleotides.1 Despite general media reports that the findings are a breakthrough on the way to artificial life, the practical utility of the technology is in generating new types of aptamers.

Aptamers are small nucleic acid oligomers selected for high-affinity binding to specific protein or nucleic acid targets. To find an aptamer that hits a given target, researchers perform a recursive in vitro selection procedure called systematic evolution of ligands by exponential enrichment (SELEX). In SELEX, aptamers that bind their targets are purified and replicated by polymerases, and then the cycle is repeated. After many such cycles, only the highest-affinity aptamers remain.

Although SELEX has been very good at generating potent aptamers, the molecules are seldom stable in vivo because they are recognized by host antiviral defenses and are rapidly degraded.

To improve the biological stability of aptamers, researchers have previously made aptamers with non-natural sugar backbones that are resistant to degradation. However, the polymerases used in the SELEX procedure do not readily recognize these non-natural nucleotides. As a result, manipulating and refining non-natural aptamers has been difficult.

Now, a team led by Philipp Holliger, group leader in the Laboratory for Molecular Biology at the Medical Research Council (MRC), has bridged the gap between SELEX and degradation-proof aptamers. The group...

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