Synthetic Molecules Created to Store, Replicate Genetic Information

Philipp Holliger, from the Medical Research Council (MRC) Laboratory of Molecular Biology’s (LMB; Cambridge, UK) protein and nucleic acid chemistry (PNAC) division, have created the first synthetic molecules that, alongside the natural molecules DNA and RNA, are capable of storing and replicating genetic information.

Dr. Vitor Pinheiro and colleagues from Dr. Philipp’s group used advanced protein engineering technology to modify enzymes, which in nature synthesize and replicate DNA, to establish six new genetic systems based on synthetic nucleic acids. These have the same bases as DNA but the ribose linkage between them is replaced by quite different structures.

In accomplishing this, the scientists demonstrated that there is no functional constraint limiting genetic information storage to RNA and DNA. Therefore, this finding has implications for the fundamental comprehension of life on Earth. As other informational molecules can be vigorously synthesized and replicated, the emergence of life on Earth is likely to reflect the abundance of RNA (and DNA) predecessors of Earth in its earliest stages.

One of the practical applications of the techniques developed by the investigators is likely to be the development of functional nucleic acids, called aptamers, with therapeutic, diagnostic, and analytic applications. Aptamers can have a number of significant advantages over the current small molecule and antibody-based therapies. For instance, they bind their target molecule with high specificity (like antibodies) but being smaller they are expected to have better tissue penetration. They have low-toxicity and low-immunogenicity and they can be chemically modified to improve their stability and pharmacokinetic characteristically.

In the past, making aptamers ‘body proof’ considerably contributed to production costs. The new HNA (hexitol nucleic acid) genetic system, developed by the LMB researchers, addresses that matter by efficiently producing molecules that are from the outset less susceptible to enzymatic degradation and better suited for therapeutic use. The development of new aptamers could be useful in the diagnosis and treatment of cancers, hematologic, ocular, and inflammatory conditions, and other diseases.

The research team included collaborators from Catholic University (KU) Leuven (Belgium), the Center for Evolutionary Medicine and Informatics at Arizona State University (Tempe, AZ, USA) and the Nucleic Acid Center at the University of Southern Denmark.

Related Links:
Medical Research Council Laboratory of Molecular Biology
KU Leuven
Center for Evolutionary Medicine and Informatics at Arizona State University