A CRISPR Way of Looking at DNA

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[This entry is inspired by a Quanta magazine post. QM is hands down my favorite source of well-written popular science treatises. And I only loved the website more when they wrote about CRISPR. Click on the image above to direct you to a video on CRISPR]

My goal is to get you excited about CRISPR by the end of this article. It is a daunting duty to get people interested in a scientific discovery. The immediate reaction of most people is to dismiss it as boring or too hard to comprehend. I sincerely believe it’s due to a lack of scientific communicators out there to stoop down to the level of the common person. This is my contribution to the thankless task of translating science for the general audience. I hope that I will not only help you understand this discovery but infect you with my enthusiasm as well.

CRISPR is an acronym for “clustered regularly interspaced short palindromic repeats.” I know this sounds intimidating for people without a background in biology but I will try my best to dissect this term for you. DNA is the material in cells that encodes information in all living organisms. Unlike the 26 letters that make up the English language, this nucleic acid language is made up of only 4 letters (A,C,T,G) called bases. Now these bases are lined up together in sequences that compose the cell’s repository of information. CRISPR simply refers to DNA sandwiches of repeating (AGAGAG, for instance) and “random” sequences scientists have found in bacterial genomes.

At first, nobody really knew what they were for. It was just that these DNA sandwiches are found in many microorganisms whose genomes have been sequenced. Their ubiquity, however, hints on a crucial biological function yet to be determined. It is the first clue to the interesting mystery that biologists want to solve. Further comparisons among the sequences led to the observation that CRISPR is always found near a Cas gene.

The Cas gene encodes for an endonuclease protein. From the terms “endo-” and “nuclease”, it means that it cuts within inside a DNA sequence. So scientists had a hunch that perhaps CRISPR is involved in cutting up DNA sequences. Naturally, this leads to the question of what does it cut? The answer to this question came when other scientists studying CRISPR realized that the ” random” sequences looked a lot like viral DNA.

The hypothesis formed from this observation was that bacteria use CRISPR like a target list of criminals to kill. It is a list generated when Cas protein gets the DNA of an invading virus. Once it has the DNA of the virus, the bacteria can recognize that sequence and destroy the viral DNA. Experiments confirmed this hypothesis and eventually found that the Cas protein uses the CRISPR sequence for specificity. It locks in like a guided missile headed towards an invading pathogenic DNA to neutralize the threat.

If you have some knowledge of immunology, you’d realize that this is analogous to the active immune response in animals. In the context of basic biology, the discovery that single-celled organisms have a complex system of detecting and destroying specific viral pathogens is mind-blowing. It questions the paradigm that microorganisms are primitive creatures capable only of simple processes.

But that’s not the end of the story. Once you comprehend how this system works, it’s easy to imagine its wide application in biotechnology. This is essentially a system that could be utilized with unlimited potential. To help you understand the implication of this discovery, remember that it’s the CRISPR that gives target specificity to the Cas protein. CRISPR is a nucleic acid sequence that we can easily change with readily available laboratory techniques. By conjugating the Cas protein with different CRISPRs, we can target any DNA sequence we want. Anything from fruit fly wings to human cancer cells is fair game for CRISPR-Cas because all organisms use DNA to store their genetic information.

Thus, CRISPR provides a precision tool for molecular manipulation. This is not just a groundbreaking theory, it has actual clinical and industrial applications that are actively being researched right now. For instance, HIV viral DNA was snipped off an infected cell using a CRISPR-Cas system. While actual clinical trials are still far off in the future, it is an important proof-of-concept that may lead to an effective cure for AIDS. Since the CRISPR-Cas system is found in many bacterial species, there are numerous variations to work with when optimizing its applications. The potential is even greater now because scientists have recently discovered a method of culturing previously unculturable cells, expanding the repertoire of microorganisms available for experimentation.

Applications aside, CRISPR illustrates a recurring theme in the Scientific research process that I want you to remember. Everything starts with a basic research that attempts to solve a seemingly uninteresting topic. Scientists initially just wanted to know why they kept seeing these DNA sandwiches in the different microorganisms they sequenced. Now we have a novel method for precision genetic engineering. The discovery of restriction enzymes follows a similar story and these enzymes led directly to a range of researches that gave us the injected insulin used by diabetics worldwide.

So the next time you hear of a boring research conducted by local scientists in your nearby university, don’t think of it as a waste of public funds. Think of it as an exercise of the primal human instinct for the pursuit of knowledge.Think of it as a potential game changer in public health and industrial development. Think of it as an investment for a better and brighter future.

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