Genetic scissors: at the cutting-edge of life

• Author: James Nurton
• Position: Freelance writer

The collaboration between Professor Charpentier and Professor Doudna brought together their expertise in pathogenic bacteria and RNA interference, respectively. It began in 2011 and was, according to Professor Charpentier, “short and intense”, but its impact will be felt for many years. Their key achievement was identifying that CRISPR, a natural defense mechanism found in the DNA of bacteria, and Cas9, an enzyme, could be programmed to cut a DNA molecule at any point.

As Professor Claes Gustafsson, Chair of the Nobel Committee for Chemistry, explained in a paper published by the Royal Swedish Academy of Sciences , “the development of this technology has enabled scientists to modify DNA sequences in a wide range of cells and organisms. Genomic manipulations are no longer an experimental bottleneck. Today, CRISPR-Cas9 technology is used widely in basic science, biotechnology and in the development of future therapeutics.”

Common terms

DNA: Deoxyribonucleic acid, a molecule present in all cells that carries genetic instructions.

RNA: Ribonucleic acid, a single-stranded molecule sometimes referred to as DNA’s “cousin.”

CRISPR: clustered regularly interspersed short palindromic repeats – arrays of repeated DNA sequences.

Cas: CRISPR-associated proteins that cleave virus DNA. There are 93 of them, one of which is Cas9.

TracrRNA: trans-activating CRISPR RNA, which enables long RNA created from a CRISPR sequence to mature into its active form.

A revolutionary tool to shape biological systems

“CRISPR-Cas9 is a powerful tool that has made gene editing faster, more accurate, cheaper and easier to operate. It’s also a socially disruptive technology with many applications including to human medicine, agriculture and biofuels,” says Dr Kathy Liddell, Director of the Centre for Law, Medicine and Life Sciences at Cambridge University in the UK. As of October 2020, 115 clinical trials using human genome editing (HGE) technologies are underway, according to the World Health Organization HGE Registry, including for widespread genetic diseases such as sickle cell disease and beta thalassemia. In March 2020, the first CRISPR-Cas9 gene therapy was administered to someone suffering from a rare condition known as LCA10, which causes childhood blindness and for which no other treatment is currently available. In this instance, the therapy was used to remove a mutation in the gene (CEP290) which causes the condition.

But CRISPR-Cas9 has also resulted in some less favorable headlines, with a long (and as yet unresolved) patent battle and ethical debates about “designer babies”. Professor Jacob S. Sherkow of the College of Law, University of Illinois at Urbana-Champaign in the United States, says this reflects the fact that CRISPR-Cas9 is “the most important advance in biotechnology in the past 40 years.” “It allows scientists, researchers and developers to precisely edit the genome of a living cell. In other words, you can edit the software that makes us alive,” he adds.

Responsible development

The two Nobel Laureates realized the magnitude of their discovery early on. Professor Doudna has spoken about how, by 2014, she felt a growing responsibility to engage in the public ethical debates. In early 2020, she told the Financial Times: “We need to be thinking about these broader implications...