Commentary: It’s in your DNA


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It is almost impossible to pick up a medical journal today without seeing an article or commentary on gene editing.

In 2013, a gene editing tool called CRISPR was able to alter the DNA of human cells in a precise manner with an easy-to-use pair of “scissors.”



Graphic with quote from Nicholas J. Petrelli, MD, FACS



CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Thank heaven, saying CRISPR is much easier!

Progress and complexities

I am fortunate enough to have the Gene Editing Institute (GEI) at our cancer center.

The GEI — directed by Eric Kmiec, PhD — allows me to see and learn the progress and complexities of gene editing.

As you all know, CRISPR has moved out of the research laboratory and into numerous clinical trials, including those evaluating its use for treatment of cancer.

What this technology has done for patients with sickle cell disease certainly would have to be described as remarkable.

However — as Dr. Kmiec reminds his lab at almost every meeting — it is critical that scientists move forward very cautiously, making sure we understand the strengths and potential side effects of CRISPR aside from the social and ethical consequences of gene editing in humans.

I’m sure I won’t do Dr. Kmiec justice, but the key entity in all of this is bacteria.

To protect themselves against invaders, the bacteria capture pieces of a virus in DNA and store them as segments called crispers. If the same invader tries to attack again, those DNA segments help an enzyme called Cas find and slice up the invader’s DNA.

Beyond medicine

In the medical profession, we are aware of the potential use of CRISPR in many diseases. However, this amazing technology also is being utilized in other areas.

For example, agriculture shows how CRISPR research and technology can come together to improve crop yield and quality. Although conventional crop breeding is much faster than it was decades ago, it is likely unable to keep up with the increasing demand for food and the global environmental challenges we face.

We also know that food allergies affect a large percentage of the population and — in some instances — can be life-threatening. With CRISPR, it could be possible to make milk, peanuts or eggs that are safe for everyone to eat.

Imagine using CRISPR to modify the DNA of wheat to remove gluten, making it suitable for patients with celiac disease.

Believe it or not, gene editing could improve the production of biofuels by algae. Strands of algae that produce twice as much fat then can be used to produce biodiesel. Until the discovery of CRISPR, algae did not produce high enough levels of fat to make the production of biodiesel economically viable.

CRISPR also could help us control the number of animal species that transmit infectious diseases. The technology can be used to create “gene drives” that ensure a genetic modification will be inherited by all offspring. Imagine what this could do for the spread of malaria.

It’s not going to surprise you as we turn toward the category of sports that editing the genome of horses to make breeds that are faster and stronger is in the making.

Researchers in an Argentina-based cloning company have focused on the myostatin gene sequence, which is crucial for the growth of muscles. The question is, do we really want to go there — and where will it stop?

Lastly, scientists are working on bringing back animals that are extinct.

The first candidate has been the passenger pigeon, once a dweller of North American forests.

Using CRISPR technology, researchers plan to introduce genes from the passenger pigeons into its modern day relative, the band-tailed pigeon. Subsequently, the hybrids will be bred for many generations until the offspring DNA matches that of the extinct species.

Does that mean that mammoths could follow? Yes, indeed.

A group at Harvard is working on bringing back the mammoth, which went extinct thousands of years ago.

The question here is, why would we want to do this? Even if we could bring back the woolly mammoth, how do we know it will survive in the present environment where climate change is a major problem?

Only the beginning

I have only touched the surface of the potential for CRISPR — or, for that matter, the technology that may be at the next level for gene editing.

For example, a recently patented genome editing tool called PASTE holds genuine promise for expanding the universe of treatable genetic diseases.

The approach combines elements of CRISPR and prime editing with a pair of enzymes designed to enable the integration of large segments of DNA without incurring double-stranded DNA breaks.

Oh boy, what kind of a world will my daughters live in?!

Stay safe.

References:

For more information:

Nicholas J. Petrelli, MD, FACS, is Bank of America endowed medical director of ChristianaCare’s Helen F. Graham Cancer Center & Research Institute and associate director of translational research at Wistar Cancer Institute. He also serves as Associate Medical Editor for Surgical Oncology for Healio | HemOnc Today. He can be reached at npetrelli@christianacare.org.

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