Aptamers are single-stranded oligonucleotides which are able to target peptides, proteins, small molecules or live cells by virtue of their well-defined three-dimensional shapes. Aptamers are typically generated by evolution of specific sequences against a given target by in vitro evolution using the process known as SELEX. Progress of this field with respect to drug development has so far been hampered by the relative large size and poor biostability of evolved aptamers composed of unmodified nucleotides, necessitating tedious and extensive post-SELEX truncation and modification approaches. LNA (locked nucleic acid) is a prominent nucleotide modification which is in the process of revolutionizing gene silencing and RNA detection. LNA however has never been included in de novo aptamer evolution. EVOLNA is an ambitious but coherent research program with the objective of transforming the field of aptamer technology. The vision is to enable evolution of aptamers that per se possess most of the desired properties, thereby alleviating the need for extensive post-SELEX procedures. This will be realized by combining the unique properties of LNA with innovative methods for LNA aptamer evolution. LNA aptamer technology is envisioned to enable evolution of aptamers displaying maximum chemical diversity, minimum size and high biostability. The developed strategies will be applicable not only towards evolution of therapeutic aptamers, which will be the main subject of this program, but also towards evolution of aptamers for biosensing, diagnostic and imaging applications. The program is at the very frontier of biotechnology research and spans the areas of chemistry, molecular biology and drug research.
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