CRISPR: Implications for materials science

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CRISPR: Implications for materials science By Philip Ball

The ascent of CRISPR The latest possibilities for editing DNA with pinpoint accuracy are transforming genetic science and may soon have biomedical implications for humans. It has been less remarked, though, that the new technology should have implications outside the

life sciences, in particular for the design and synthesis of new materials. Not only might it streamline the modification of living organisms so that they can produce useful materials or their precursors, but it can also expand the possibilities for using DNA itself as a constructional material.

How

CRISPR works

1. The Cas9 protein forms a complex with guide RNA in a cell

Cas9

2. This complex attaches to a matching genomic DNA sequence adjacent to a spacer (yellow segment)

Guide RNA

DNA has become a versatile polymeric substrate for making nanotechnological structures and artificial molecularscale machinery for computation, pattern formation, and nanoscale assembly. For several decades now, these efforts have drawn on methods developed in and for biotechnology, and similarly they are likely to find ways of exploiting the advantages of the new technique called CRISPR/Cas9 for manipulating DNA. Devised in 2012, CRISPR/Cas9 exploits a natural DNA-snipping enzyme in bacteria, Cas9, to target and edit particular genes. The target sequence of the DNA is recognized by a matching sequence on a “guide RNA” molecule carried alongside Cas9. This enables, for example, modified forms of the respective genes to be pasted into a genome. The method, and related approaches using other enzymes of the Cas family, could potentially supply a powerful way to cure diseases caused by mutations of one or a few specific genes, such as muscular dystrophy and thalassemia. A US clinical trial to assess the safety of CRISPR/Cas9 in a form of cancer therapy that enlists the body’s immune response to fight tumors has already received approval. The discovery of the technique, for which the key contributions are generally attributed to biochemists Emmanuelle Charpentier, Jennifer Doudna, and Feng Zhang, is now widely tipped for a Nobel prize.

DNA nanotechnology and materials

3. The Cas9-RNA complex cuts the double strands of the DNA

Programmed DNA

4. Programmed DNA may be inserted at the cut Credit: MRS Bulletin

CRISPR-Cas9 is a method of genome editing that exploits a natural DNA-snipping enzyme in bacteria, called Cas9 (CRISPR-associated protein 9) to target and edit particular genes. CRISPR stands for Clustered regularly interspaced short palindromic repeats, which are segments of DNA of a particular structure found widely in bacteria and archaea (prokaryotes). In the wild, the CRISPR-Cas9 system is part of the prokaryotic immune system, which can snip out of the genome DNA acquired from foreign sources such as phages (bacterial viruses). The same molecular machinery is now being used to enable genetic material to be cut from and pasted into the genomes of other organisms, including eukaryotes such as humans. It