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The Fault in Our Genes: How CRISPR Could Eradicate Genetic Disorders

tumblr_inline_npac6hpGFs1qzgziy_540Each one of your 37.2 trillion cells contains all the instructions to make a complete human. These instructions are governed by a code made up of four letters: A, T, C and G. These are nucleotides, the components of deoxyribonucleic acid, or DNA.

A few simple rules apply to this code: A always pairs with T, and C always pairs with G. From there, virtually endless combinations of letters can form an almost endless number of genes – the basic units made of DNA that govern each of our inherited traits, from the color of our eyes to our risk of developing heart disease.

What would you do with the power to re-write the code that makes you, you?

That question recently moved from the speculative realm of science fiction to the all-too-real minefield of medical ethics, because scientists are now able to selectively modify genes with speed and ease, using a molecular system called CRISPR-Cas9 (often shortened simply to CRISPR).

CRISPR was not actually invented by scientists. Its discovery began as an observation made in the 1980s while studying the bacterium that causes strep throat, Streptococcus pyogenes: bacterial DNA sometimes contained a strange pattern of sequences that repeated again and again, which they called Clustered Regularly Interspersed Short Palindromic Repeats, or CRISPR (pronounced ‘crisper’) for short.

It was later discovered that these sequences matched the DNA of viruses, and CRISPR is actually a form of bacterial immunity that protects against them (yes, bacteria can get viruses too!). The repeating strands are actually sections of viral DNA that the bacterium has taken as a kind of genetic snapshot, which it uses to recognize the virus in future. If it recognizes a virus, CRISPR-associated proteins (Cas for short) are deployed, acting as molecular scissors that slice up the virus’ DNA and stop it in its tracks.

To sum up, as a bacterium’s CRISPR regions fill with virus DNA, they become a sort of molecular rogue’s gallery. The bacterium can then use this viral DNA to turn Cas proteins into precision-guided weapons against the virus in future.

What scientists have now achieved is to take advantage of this bacterial defense tactic and use it to target specific genes by adapting the CRISPR-Cas9 system to work in organisms other than bacteria, including mammalian cells. This is basically a cut-and-paste approach to gene editing, and it is nothing short of revolutionary.

If this cutting and pasting of DNA is performed in stem cells, which give rise to many different cell types, the edits would be carried on throughout the cell’s lineage, eventually into whole tissues, organs, or entire organisms.

Speaking to Quanta magazine back in February, Jennifer Doudna, one of the scientists credited with discovering how CRISPR-Cas9 could be used to edit genes, recalled the spine-chilling moment everything clicked. “Once we understood it as a programmable DNA-cutting enzyme, there was an interesting transition,” she said.

“We thought, ‘Oh my gosh, this could be a tool.’”

The technique could potentially develop, as stated by Edward Lanphier in The Guardian last May, “a functional cure for HIV.”

If we liken Watson and Crick’s discovery of DNA in 1953 to the discovery of a new language, the discovery of the CRISPR-Cas9 system can be likened to taking a red pen to that language, and editing it to suit our purposes.

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3D artwork of dividing cancer cells.

However, we are far from writing Shakespeare. Our command of the language of DNA is still rather poor. “Specificity is the greatest concern for those using CRISPR-Cas9 methods,” said Anja Smith, Director of Research and Development at Dharmacon, a unit of GE Healthcare Life Sciences. “Here the concern is that you may ‘cut’ or edit the genome where you intended to, but you may also effect the genome in other places you did not intend to or may not know about.”

“Reports have been mixed in terms of how specific or non-specific the technology is,” added Matthew Ferris, Director of Portfolio Management and Customer Care at Dharmacon. “But of course everyone is concerned that the only change they are making in the genome is the intended change, and not another change somewhere else in the genome.  This is particularly important for therapeutics.”

Medical ethicists have already thought long and hard about the prospect of human customization. According to UNESCO’s Universal Declaration on the Human Genome and Human Rights, interventions in human DNA “could be contrary to human dignity”.

So we aren’t likely to see custom-made babies any time soon, but the potential for the technique to eradicate genetic defects that lead to disease is enormous.

The discovery of CRISPR-Cas9 as a gene editing tool was a starting gun for scientists around the world, now in a race to harness the power of the technique to not only treat cancer and serious genetic diseases but also eradicate disease-carrying mosquitoes, ticks, invasive plants, and a host of other modern plagues.

Anja added, “We can manipulate genes quite precisely now.  The easy part is to switch proteins on and off; an even more interesting application of CRISPR-Cas9 is to change protein expression in order to create, for example, complex synthetic gene circuits.”


3D artwork of a bacterium. Credit: Getty Images.

“The efficiency is not yet as high as in model organisms like bacteria and yeast but it’s far better than it was before CRISPR-Cas9 and it will only improve.”

Dharmacon is busy developing technologies for gene expression and editing, including CRISPR-Cas9.

One such technology that has already come out of GE is called Edit-R, a platform that significantly reduces the time it takes to generate the sequence that guides Cas9 to cut in a particular location along a strand of DNA.

The applications of CRISPR are far more wide-ranging than human medicine. With it, scientists technically have the power to genetically modify any living thing under the sun. This could not only change us, but the entire world we live in.

More Information

Ethics of embryo editing divides scientists

The Ultimate Coders: Revolutionary New Tool Can Rewrite DNA


UNESCO’s Universal Declaration on the Human Genome and Human Rights