CRISPR Cas9: The Ultimate Gene Modification Tool

CRISPR is something you have probably never heard of if you are not interested in biological and health care technology. To the sworn techies, however, this is a household name that represents a tool that may change the game forever.
What may not be clear to virtually everyone regardless of their grasp of scientific developments is why all of a sudden the technology has become such a big deal when scientists have been fiddling with genomes since the 80’s. Well, hopefully at the end of the article you will have a global idea.

Make sure to leave your comments at the bottom of the page and let us know what you think about this medical breakthrough.

What is CRISPR?

CRISPR refers to the odd DNA sequences that identify pathogens and fight them when they attack body cells.

The name – which is pronounced “crisper” – stands for Clustered Regularly Interspaced Short Palindromic Repeats.

Um weird, right?

You could be pardoned for thinking so, but if you took a second glance at the phrase you would realize that it is a brief description of the general structure of the DNA sequences.
Normally, they are clustered and occur at regular intervals. If labeled with letters, they portray palindromes that occur in near-perfect repetitions.

CRISPR was first detected back in the 80s by a group of scientists led by Francisco Mojica during a random study on bacteria and archaea.

The odd DNA sequences drew their attention, and studies ensued to find if the structure was adapted to any particular purpose.
Expected to draw a blank after a series of failed attempts, scientists led by Philippe Horvath finally in 2007 conclusively showed that the sequences were for viral defense.

So then CRISPR is just a DNA strand?

Well, you wouldn’t be wrong if you said it is but then again you wouldn’t be entirely right. It isn’t important either way.
What you need to know is that it has enabled gene editing, splicing, and experimentation and that is why it is a big deal.

By understanding its role in genomes and how it works to protect the body against disease-causing organisms you’ll get to know how it enables the said functions. I’ll give you a superficial idea.

An organism has to learn how to deal with a new disease just in case it happens more than once.
The CRISPR sequences study the virus and even steal a few strands from its DNA to familiarize with it.

If the disease is detected for the second time, the body attacks it with a premeditated enzyme or group of enzymes as the DNA seems relevant.
Just for the record, virus attacks DNA directly so there is no way an organism’s DNA can miss out on an incoming attack.
Cas is the name of the protein released by CRISPR to twine with viral DNA and weaken it during an attack. And that brings us to CRISPR Cas9.

What is CRISPR Cas9?

CRISPR Cas9 is a super accurate technique through which medical practitioners can constructively modify the blueprint of targeted DNA.

So, yes, genetic engineers could now follow the same “telegraph” used by CRISPR to protect the body against viral infections to do the same.
In fact, they can do more with it; they can communicate right about anything from shutting down a gene to turning dormant genes on. And this is regardless of the gene’s nature. It can be viral or not.

CRISPR Cas9 was invented back in 2012 by researchers at the University of California but only burst into fame little over one year ago when scientists started applying it on human cells.

It is during that time when they announced having successfully used it to correct hepatitis-C-bearing cells in humans.

Also, there was the failed attempts to do away with a notorious disease-causing gene in the embryo.

This basically made for the first time ever anyone announced they were going to try genetic engineering on human embryos.
Plausibly, it drew outrage from ethicists and scientists who didn’t reckon there was enough reason to try on a human body a technology of unknown consequence over existing genetic engineering techniques.

To give you a clearer picture of what we are talking about, here is what we mean by genetics and genetic engineering.

Genetics – Genetics is a field of Biology which deals with genes, genetic variation, and heredity in living organisms.
Genetic Engineering – Genetic engineering, on the other hand, involves artificial modification of an organism’s genetic material (DNA) in a bid to add traits that the organism lacks.

Since discovering the CRISPR Cas9, the genetic engineering department has been on the go trying to find more control over the enzyme and even build RNA guides for them or supplemental enzymes called Cpf1 which can perform infiltration and extraction at zero mutation risk.
Even without those auxiliary tools, however, CRISPR Cas9 was already theoretically a way more superior technique of gene editing than its age-old counterparts.

How CRISPR Cas9 Lines Up Against Its Rivals

Its two main genetic modification predecessors are transcription activator-like effector nucleus (TALENs) and Zinc Finger Nucleases (ZFN).

It holds an edge over both of them thanks largely to its ease of use and exactitude. There is literally little to no chance of interfering with untargeted components of a DNA strand when using CRISPR/Cas9, according to experts.

While TALENs and ZFN have their upsides in the ability to recognize longer and more complex DNA sequences and higher specificity, they are outweighed in almost every other remaining aspect.

One of them is the fact that scientists have to custom design TALEN or ZFN each time they want to modify DNA. Also, they often have to create a couple of them – all of which they will try and find the one that works best, or works at all, for that matter.

With CRISPR Cas9, it’s way easier to come up with an RNA guide sequence, and one which is more likely to work.

What’s more, it can be used on any organism, which is quite a breakthrough on its own.

Since time immemorial, scientific experiments have been performed on only a set of laboratory animals whose systems scientists have studied for years, have grown fond of and can easily and successfully fiddle with.

Some of those organisms include fruit flies, rats, zebrafish, mice and a nematode known as C. elegans.

CRISPR Cas9 has theoretically enabled the genetic modification of any living creature that can fit in a lab.
Humans are no exception, but as I pointed out earlier, concerns over what the long-term effects of this technique of genetic editing have become a hindrance.

Since 2013, researchers have been trying to find and eliminate any associated side effect and of course make the technology more acceptable and practical, but definitely it will take longer than a few years to see genetically modified humans.

What we are likely going to see more are other genetically modified animals outside those reared for lab tests.

Combined with other biology tools, CRIPSR/Cas9 could soon become a vital component in ecology and conservation. For instance, there could be introduced genes that can gradually eradicate malaria-causing mosquitoes.
Recently, on a similar note, the FDA allowed Oxitec – a British biotech firm, to release genetically modified mosquitoes to fight the Zika virus in Florida.

This came after the government department itself conducted a research after the company’s proposal and found out that any toxic effects in humans caused by bites from the GMO mosquitoes could most likely be negligible.

The basic aim of the approach is to finish off the Aedes aegypti female mosquito (also known as the Yellow fever mosquito) which carries the Zika Virus by having them copulate with the GMO males whose genes have been edited to produce offspring that would not survive outside the lab.

The company guesstimated that it would have done away with 90 percent of the Zika carriers by the end of the first six months.

If this one goes through, then malaria mosquitoes – which are responsible for 600 million infections and one million deaths worldwide each year – could be lined up for the same fate.

And who knows?

Premature baldness, sickle cell anaemia, and albinism could be next!

CRISPR Cas9 on Humans – Is it Possible to Edit Human DNA Now?

In June, a federal biosafety and ethics panel gave scientists from the University of Pennsylvania the green light to use CRIPSR to create genetically modified cells to combat three forms of cancer.

The problem is that the technology may not be applied on a real patient until 2017 as lab tests are still ongoing.

Also, the breakthrough technology seems to work only on some types of cancers mostly blood cancers such as Leukemia.

Plausibly blood cancers are the deadliest but then they may not be as prevalent as breast, prostate and lung cancers.

In China, there is an ongoing experiment http://www.nature.com/cr/journal/v25/n2/full/cr2014158a.html which may debut gene modification in humans if everything goes well.

Volunteering lung cancer patients will be injected with cells modified with CRISPR to kill off cancerous cells any time from August.

So can we modify anyone’s DNA?

Apparently, as you may have realized, we are not yet there. It’s just this bunch of promising experiments and approvals from ethical authorities that our hopes rest on.

The closest we have come is the genetic modification in a pair of monkeys to rectify faulty genes that went down a success.
Well, there are several animal experiments out there that were similarly successful but this is special because it worked in a monkey/primate, which is usually considered a big deal.

So, What Next Now for CRISPR Cas9?

CRISPR is an almost confirmed remedy for certain genetic disorders in humans and animals.

There are a a number of reasons why its use on humans has been pushed back for so long, with the main one being the numerous unknowns that may ensue.
For instance, scientists haven’t come up with any solid report showing the likelihood and frequency of off-targeting.

In all probability, they can’t predict it.

Also, there are ethical issues such as the prospect of giving rise to a genetically edited generation that wouldn’t be happy with the fact that they were embryonically modified without their consent/approval.
Perhaps the biggest fear thus far is the possibility of humans using CRISPR Cas9 to develop superior humans or what has been mostly referred to as designer babies.

While the better part of why it is a fear remains subjective, some concerns have shown that the world with designer babies is not a good prospect.

For one, it may create a massive social gap as designer babies will most likely be better looking, smarter, disease-resistant etc. with unmodified babies being considered inferior.
CRISPR Patent

Broad Institute the current owners of the CRISPR patent were in January 2016 rocked with an interference appeal from Emmanuelle Charpentier, the University of Vienna and the University of California who claim to have been the first to come up with the technology and not Broad Institute, MIT and Harvard.

Broad in a statement have maintained that they are indeed the rightful owners of the patent and believe that the United States Patent and Trademark Office (USPTO) will eventually refuse the appeal and uphold their initial decision.

In a new twist of events, however, a former Broad Institute employee, Shuailiang Lin, reveals in an email that Broad were not the inventors of the technology and that they used false proof to confuse USPTO into granting them the patent.

The email was sent back in 2015 by the junior Chinese scientist to a University of California, Berkeley professor in exchange for a job.

The information on the email has looked quite reliable to many not just because Lin is a former employee at Broad Institute but also because he is listed among the inventors in Broad’s initial filing of December 2012.

While this is irrefutably quite a notable issue, it remains purely a commercial battle which has almost no implication on anyone outside the claimant companies and firms such as Editas, to whom the technology has already been licensed.

Conclusion

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