CRISPR — Is there any good reason to edit an organism’s DNA?

CRISPR

Key facts about CRISPR

  • CRISPR is a cost-effective technology to edit the organism’s DNA easier than ever before.
  • It was adapted from a natural bacteria defence system.
  • The gene drives alternative makes possible to pass edited genes to offspring.

Description

CRISPR is a technology that allows altering DNA sequences and modify gene function faster, easier, cheaper and more precise than previous genome editing methods.

DNA is a molecule which carries the instructions of how a living organism should growth, develop, function and reproduce. DNA functions as a storage device of biological information and RNA function as a reader that decode this information. The technology to modify these molecules is called genome editing.

There were several recognised genome editing methods before, but CRISPR has revolutionized the field. The reason for such a revolution is its simplicity, versatility and precision. CRISPR stands for “clusters of regularly interspaced short palindromic repeats”. The key words here are “interspaced” and “repeats”.

How works

The term CRISPR was used for the first time in 1990 to refer to unknown repeating sequences observed in different bacteria DNA. Later on, scientists found out that indeed these sequences are part of the bacteria immune system. When bacteria defeat a virus after a viral infection, they chop the virus DNA and store it in their own bacteria genome in CRISPR spaces.

The bacteria use these pieces of information to defend themselves from future viral attacks.  Whenever a new viral infection occurs, the bacteria produce an enzyme (Cas9) that check if the new attack match with the pieces of RNA viruses already stored. When the enzyme finds a match neutralize the virus by destroying that part of the genetic code.

Now scientists have figured out how all these mechanisms are triggered, and we can engineer the whole process to edit any genome sequence. In short, the CRISPR technology works like a pair of molecular scissors where only two components are needed: a guide RNA and the Cas9 protein. First, a specific gene is target base on RNA-DNA base pairing. Second, the gene is cut through the enzyme activity (Cas9). Third, a new sequence of engineered DNA can be added by using the cell’s own DNA repair machinery.

In that way, pieces of genetic material can be added, altered or deleted, easier than never before. With the current levels of efficiency, the use of gene editing methods for therapeutic use is a realistic future scenario.

Potential applications

CRISPR is a very young technology. For now, it has been used only in research labs. However, it opens so many possibilities that many pharmaceutical and biotech companies are investing in this technology. There are many potential applications of this technology, but all of them fall in three main branches: agriculture, industrial biotechnology and human health.

The most direct application of CRISPR-technology is to study the genes function. Thanks to the human genome project, since 2003, we have identified all the genes in the human DNA, but we do not know yet which is the function of each of them. Since CRISPR is very precise, scientists can rapidly delete individual genes and analyse which traits are affected.

Agriculture

Another application within reach is to improve crops. With a technology like CRISPR, it is possible to make fruit more tasty and nutritious. But not only that, it is also potently possible to remove the allergens from peanuts or improve drought tolerance. Even create hornless dairy cows.

Health

Scientists are also working on correcting genetic defects and stopping genetic diseases. Although there is still a long way before seeing the first tests in humans, several research projects are seeking to erase genetic diseases like hypertrophic cardiomyopathy or HIV. In addition, CRISPR technology is a powerful tool to develop new drugs in a faster and cheaper way.

Biotechnology

Finally, this technology could be used to modify entire species by using gene drives. These are genetic systems, which increase the chances of a particular gene passing on from parent to offspring. In this way, an altered gene can be spread through entire populations very fast. This is interesting for example, to make mosquitos more resistant to the malaria parasite, preventing its transmission to humans, to eradicate invasive species or to reverse pesticide and herbicide resistance.

History and future

In 1987, a group of researchers reported the existence of repeated sequences of DNA without purpose known in a specific type of bacteria. In 1990, the same sequences were observed in very different bacteria and the sequences were named as CRISPR. Following investigations, found that these sequences were virus DNA, and they formed part of the bacteria immune system.

By 2011, scientists puzzle how all this immune system works and in the following year, the final breakthrough was reached. Scientists discovered how to engineer all this bacteria defence process to edit any genome at any place they wanted. Although the understanding of the whole mechanism was conducted by separate research groups, 2012 is considered the official year of discovery of this technology as a genome-editing tool.

Since then, research using this technology has exploded to optimize it and make it more efficient and accurate. Much research is still needed to understand the full implications of this technology in more complex organisms.

It is foreseeable to see the first applications on agricultural products although the biggest challenges will be to handle this technology to one day been able to edit the human genome.

Controversies

During the past decade, technological breakthroughs in genome editing have moved the primary research goal in biotechnology from treatment to modification and cure, bringing gene therapy and precision medicine into a new era. CRISPR is easier, faster and about four times more cost-effective than the previous best genome-editing tool, known as TALENs. That has accelerated the pace of scientific research in this field. However, there are still many challenges to deal with and new ones have arisen.

Precision

So far, scientists have performed most of the genome editing research on cells and animal models and have demonstrated that the technology can be effective in correcting genetic defects. But there are several hurdles before to start safe clinical trials on humans. CRISPR has an accuracy of about 70%. That means that there is a 30% probability of unintentional modifications of non-targeted genes. This can lead to the introduction of unintended mutations like the creation of a new disease. That is why many experts argue that experiments in humans are premature.

Gene drives and germline editing

Another uncontrolled potential risk is the use of gene drives, in the case of spreading beyond the target population passing to other organisms through crossbreeding. Furthermore, the use of this technology in mass rise problems that go beyond the biology, political and governance problems.

A variant of the gene drives is the germline editing, which consists in modify genetically human embryos and reproductive cells such as sperm and eggs. Such application will raise problems in off-target effects and unintended consequences for future generations, but also ethical and legal challenges. To address these concerns, the National Academies of Sciences, Engineering and Medicine have published a report with guidelines and recommendations for germline editing.

The ethical concerns go beyond the technological challenges, but in any case open interesting debates about if we should make changes that could fundamentally affect future generations without having their consent, or the opposite case, if it is ethical to not modify the genes to cure potential diseases of future generation even when it is in our hand.

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Now it is your turn.

  • What do you think about the idea of editing the DNA of an organism?
  • How far do you think we should go with this technology? Only to cure genetic diseases or there is no threshold for human enhancement, for example, to design taller and smarter humans?

Leave us your opinion in the comments.

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Links

  1. History of CRISPR — Scientific study
  2. Applications of CRISPR technology — Scientific study
  3. Guidelines and recommendations for clinical trials for genome editing of the human germline — Report
  4. Human Genome Project — Website
  5. TALENs — Scientific study

Author: Enrique Morales Orcajo, PhD

I am an engineer, scientist, and traveler based in Europe. I write about how to consume and digest scientific studies in a practical and efficient way. My goal is to help you make more sound scientific judgments.

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