Introduction to Genome, Gene Editing and CRISPR/Cas9

Genome Editing-CRISPR babies controversy

On 25 Nov 2018, He Jiankui, a Chinese scientist surprised the world by announcing that he had created the first gene-edited babies by secretly using CRISPR technology (he admitted that he had kept his university in the dark).

He drew sharp scathing criticism from the scientific community and was condemned by people worldwide but the scientist defended his actions. Many believe that he had crossed a line by editing the genome of embryos, thereby affecting future generations. Appalling, abhorrent, irresponsible, reckless, and unethical were some of the words used to describe his action.

Post the announcement, #crisprbabies became a trending topic on Twitter and started a raging debate on the implications of this technology. Questions were raised on the lack of transparency and self-regulation by the medical community.

In order to truly understand the magnitude of the event and constructively participate in this debate, it is essential to understand the science behind gene editing.

What is a Genome and Gene Editing?

genome is the genetic material of an organism and it consists of DNA (or RNA in RNA viruses). The genome includes:

Gene editing (or genome editing) is a method that allows scientists to change the DNA (thereby modifying the genetic material) of many organisms, including plants, bacteria, and animals. Scientists can remove, add, or alter particular locations in the genome. This editing of DNA can lead to changes in physical traits, like eye color, and disease risk. Think of it as repair mechanics for fixing defects caused by DNA double stranded break (DSB).

Why study the genome?

The study of the genome is called genomics. A single gene or multiple genes can cause major changes to a living organism. By studying the genome, we are able to learn how genes impact the body, predict how similar changes in human genomes might affect the human health. It is particularly useful for studying diseases as it has potential for powerful applications in the prevention and treatment of human diseases.

Why are we looking to edit the genetic code?

Most of the current research on genome editing is done to understand diseases using cells and animal models. Genes are introduced or removed in research animals (such as fruit flies, mice, zebrafish) to study the effects on the living organisms. Understanding more about diseases processes helps in the development of new treatments.

How does Gene editing work?

Commonly, restriction enzymes (or nucleases) are used to effectively cut DNA, but they tend to generally recognise and cut it at multiple sites. To overcome this challenge, scientists had to develop a method to create site-specific DSB. They discovered and bioengineered three distinct classes of nucleases:

  • Zinc finger nucleases (ZFNs)
  • Transcription-activator like effector nucleases (TALEN), meganucleases and
  • CRISPR/Cas9 system

The CRISPR/Cas9 system has generated a lot of buzz and excitement in the scientific community, especially in the fields of molecular biology and genetics for its more accurate, more efficient, faster and cheaper than the other existing genome editing methods.

What is CRISPR/Cas9?

CRISPR (pronounced “crisper”) is short for clustered regularly interspaced short palindromic repeats, a family of DNA sequences found within the genomes of prokaryotic organisms such as bacteria and archaea. Cas9, short for CRISPR-associated protein 9, was adapted from a naturally occurring genome editing system in bacteria. Gene editing tech has been developed since the late 1900s. In 2009, a new genome editing tool called CRISPR was invented.

How does CRISPR/Cas9 work?

In nature, bacteria capture snippets of DNA from invading viruses and then use these snippets to create DNA segments called CRISPR arrays. These CRISPR arrays allow bacteria to “remember” the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA and then use Cas9 or a similar enzyme to cut the DNA apart, which ultimately disables the virus.

The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short “guide” sequence that attaches or binds itself to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. Like in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location. After the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material. Existing segments can also be replaced with customized DNA sequences. Although Cas9 is the enzyme that is used most often, other enzymes like Cpf1 can also be used.

In simple terms, it uses a pair of ‘molecular scissors’ like the Cas9 enzyme to cut DNA’s two strands. The precise target to cut is located using the attached RNA, so that bits of it can be removed or added. Once the cut is made the DNA begins to repair itself. But the natural repair method is error-prone and it can cause bits of DNA to be added or deleted and can thereby cause a change in the gene works at that location. Under certain conditions, it may even be possible to insert the desired DNA sequence to replace what was originally there (This is a slightly more complicated process). Using this process, it is possible to edit the genome in several places at once.

Watch this video made by the McGovern Institute for Brain Research – MIT illustrating how CRISPR-Cas9 works.



What are the potential applications of gene editing and the CRISPR system?

Gene therapies (treatments involving genome editing) are being developed to prevent and treat diseases in humans. Gene editing holds promise in the treatment and prevention of

The two categories in gene therapy are:

  • Germline therapies change DNA in reproductive cells (sperm, eggs, genes of an embryo). Changes made to the DNA of reproductive cells are passed down to future generations
  • Somatic therapies target non-reproductive cells and affect only certain tissues of the individual who is treated. These changes are not passed from one generation to the next

In 2015, scientists successfully used somatic gene therapy to treat Layla, a one-year old girl in the United Kingdom, to help her fight leukemia, a type of cancer. In this scenario, instead of CRISPR, scientists used another genome editing technology called TALENs to treat Layla and this therapy saved Layla’s life. Doctors had tried various other treatments prior to this, but none of them worked.

Note: Scientists received special permission to treat Layla using gene therapy. Treatments like the one that Layla received are still considered experimental because the scientific community and policymakers still have to address technical barriers, safety and ethical concerns surrounding genome editing.

CRISPR has also been used by researchers to edit the genes of a variety of animals to create virus-resistant pigsheat-tolerant cattle and fatter, more muscular lambs.

Is gene editing safe?

Although CRISPR is considered an improvement over older genome editing technologies, it is not perfect. For example, sometimes genome editing tools can cut in the wrong spot. Scientists are not yet fully sure how these errors might affect patients. Assessing the safety of gene therapies and improving upon genome editing technologies is a prerequisite to ensure that this technology is ready for use in patients.

This is a field that is still being explored and it is to be determined whether this is a safe and effective approach for treating people.

What are the ethical concerns surrounding gene editing?

Apart from the safety issues mentioned above, certain ethical concerns also arise when editing the genome using technologies such as CRISPR-Cas9 to alter human DNA. Using Germline cell and embryo genome it may be possible to use the technology to enhance normal human traits (such as height, intelligence, etc) but it also raises several ethical questions such as:

  • Should genome editing be allowed for treatment only for preventing or curing certain diseases or can it also be used to enhance traits, such as athletic ability or height? Is that okay?
  • Is there any scenario where germline cell editing can be allowed? (as edits are passed down through generations)
  • In the case of an embryo, it is impossible to get permission from the embryo for treatment, so is it okay to use gene therapy? Is getting permission from the parents enough?
  • Will gene therapies be expensive? Are only the wealthy class be able to access and afford them? This could worsen the existing health inequalities between the rich and poor.

Based on these concerns about ethics and safety, germline cell and embryo genome editing are currently illegal in many countries.

Watch world renowned evolutionary biologist, and author Richard Dawkins explain The Dangers of CRISPR, Designer Babies, and Artificial Genetic Mutation

You can also watch this video on how Genetic Engineering Will change Everything Forever by Kurzgesagt


Useful Links:


Scientific journal articles for further reading

  • Lander ES. The Heroes of CRISPR. Cell. 2016 Jan 14;164(1-2):18-28. doi:10.1016/j.cell.2015.12.041. Review. PubMed: 26771483.
  • Komor AC, Badran AH, Liu DR. CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes. Cell. 2017 Apr 20;169(3):559. doi:10.1016/j.cell.2017.04.005. PubMed: 28431253.
  • Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014 Jun 5;157(6):1262-78. doi:10.1016/j.cell.2014.05.010. Review. PubMed: 24906146. Free full-text available from PubMed Central: PMC4343198.
  • Gupta RM, Musunuru K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest. 2014 Oct;124(10):4154-61. doi: 10.1172/JCI72992. Epub 2014 Oct 1. Review. PubMed: 25271723. Free full-text available from PubMed Central: PMC4191047.
Author: Blog Desk
Blog Desk comprises many freelance medical and science writers with over a decade of experience in journalism. They have masters qualifications in journalism, science and management and have contributed significantly to the building of this portal. The authors can be contacted at blogdesk (at) skillmd (dot) com.

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