Stories about a mysterious tool that can cut out and replace genes have crept out from behind the lab walls and entered boldly into the public spotlight. Nowadays, CRISPR is everywhere. And we cant help but let our imaginations wander, especially when the questions posed by this novel gene editing technology come straight out of a sci-fi movie.
Can we edit out bad genes that cause diseases in humans and replace them with healthy ones? Might parents be able to design babies to their liking, with a certain hair or eye color, personality, or intelligence level? Could we engineer animals so they cant pass on deadly diseases to us? Can we even add or remove epigenetic marks on genes of our choice to control the expression of lifes code and, perhaps, our very behavior?
The precise power of the CRISPR-Cas9 system has created exciting yet controversial opportunities for genetic and epigenetic editing. Although we certainly dont have all the answers, the intriguing questions require further exploration and a deeper look into the near and distant possibilities for our society. As endless as the opportunities may appear to scientists and laypeople alike, some are more realistic than others. Its crucial we trim the hype from the realistic capabilities of CRISPR, as we usher in what some may call the golden age of genetic engineering.
The start of CRISPR
You know when you pick up a suspense novel, and read the first chapter, and you get a little chill, and you know, Oh, this is going to be good? It was like that. Jennifer Doudna, Ph.D. Credit:The New York Times.
Since the beginning of CRISPRs recent discovery as a precise and simple gene editing method, interest in its potential to improve our quality of life has skyrocketed, and with no end in sight. A similar excitement was expressed by one of the co-inventors of CRISPR, Jennifer Doudna from University of California Berkeley.
In 2011, Doudna was approached at a microbiology conference in Puerto Rico by a researcher from Max Planck Institute for Infection Biology, Emmanuelle Charpentier. The two started a conversation that laid the ground work for arguably one of the greatest collaborations, which spurred the invention of CRISPR.
I had this feeling. You know when you pick up a suspense novel, and read the first chapter, and you get a little chill, and you know, Oh, this is going to be good? It was like that, Doudna told The New York Times in 2015.
Surprisingly, the investigation of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) in bacteria is not a new thing. Researchers have been exploring these repeated sequences since the 1980s, but their function was unknown at the time. Then, scientists slowly started to uncover clues about their purpose, which pointed to a built-in adaptive immune system that bacteria used to combat invaders such as viruses.
Within the past few years, researchers like Jennifer Doudna and Emanuelle Charpentier, along with postdoc researcher Martin Jinek, have been tapping into the gene-editing possibilities of the CRISPR-Cas9 system. Meanwhile, Feng Zhang from the Broad Institute and MIT was eager to show that the system worked in mouse and human cells, which he accomplished in his paper published in 2013. He even created an alternative genome engineering method called CRISPR-Cpf1, which may improve the tools precision and power.
Recently, the two groups of researchers entered a fiery battle for a CRISPR patent and the scientific community called for a moratorium on using CRISPR to edit the human germline for fear of unknown repercussions as a result of making heritable changes that could shift the gene pool. It will surely be intriguing to follow the progression of this gene editing system and its uncertain what the future holds.
How it works
The CRISPR-Cas9 system targets precise gene sequences and removes, adds to, or changes them with the help of two components: an enzyme called Cas9 and guide RNA (gRNA). Its based on the naturally occurring ability of bacteria to recognize and destroy invading viruses via a genetic memory.
SEE ALSO: The Epigenetics Behind the Flu
Cas9 acts as the scissor that snips the DNA and the RNA guide is a tailor-made sequence that ensures Cas9 is cutting in the right place. Researchers are able to program the guide RNA with any sequence of the genetic code they desire in order to lead Cas9 to the proper location.
Other techniques for editing DNA, such as TALENs and zinc finger nucleases were explored by researchers around the same time, but these methods have a much lower level of precision and are significantly more cumbersome. Unlike other techniques, CRISPR can even target multiple genes at once. The beauty of this gene editing system is how relatively simple, accessible, and incredibly precise it is. However, even among the accomplishments there are certainly limitations.
CRISPR accomplishments
As young as the technology is, scientists have been working feverishly with the CRISPR-Cas9 system in several applications. In one study published in PNAS, a group of researchers edited out a gene sequence in mosquitos and replaced it with a DNA segment that rendered them resistant to the parasite that causes malaria, known as Plasmodium falciparum. This could prevent mosquitos from transmitting the disease to humans entirely. Interestingly, when these malaria-resistant genetically modified mosquitos mated, they passed on the resistance to nearly 99% of their offspring. This was true even if a modified mosquito bred with a normal one.
A study conducted by a Chinese research team led by geneticist Lei Qu at Yulin University also demonstrated the successful use of CRISPR to bulk up livestock. They manipulated goats DNA to make them more muscular and produce more wool, in the hopes of bolstering the goat meat and cashmere sweater industry in Shaanxi, China. We believed gene-modified livestock will be commercialized after we demonstrate [that it] is safe, Qu predicted in an article by Scientific American.
Another group of researchers were able to edit out a genetic mutation in mice that causes a disease known as retinitis pigmentosa (RP), which can ultimately lead to blindness. Although not yet approved for use in humans, they were able to restore the mices vision and are hopeful for its therapeutic application in people. They recently published their results in Nature.
Not only can scientists edit genes using CRISPR, but they may be able to change the epigenome using CRISPR as well. Many diseases are not caused by a single genetic mutation but rather disturbed gene expression profiles. Harnessing the ability to edit epigenetic marks could drastically broaden our ability to cure a much wider range of disorders. In theory, perhaps editing our epigenome could allow us to cherry-pick more desirable behaviors.
Researchers can also utilize the power of next generation sequencing to perform chromatin immunoprecipitation sequencing (ChIP-seq) with a CRISPR/Cas9 antibody. The precise, high throughput capability of this method is especially promising because of the target efficiency of the Cas9 enzyme in conjunction with multiple guide RNAs, which can be used simultaneously for multiplexing. Not only can ChIP-seq be useful as an unbiased method for detecting on-target effects of the CRISPR-Cas9 gene editing system, but it might also be used to pinpoint how the system might miss the mark, which would be helpful when developing the system for therapeutic application.
Recently, researchers used the CRISPR-Cas9 system to add acetyl groups to histones, carrying enzymes to certain locations on the genome. Histone modifications, including histone acetylation and histone methylation, have the ability to remodel chromatin to make genes more or less accessible, influencing their expression. Other research suggests we may modify DNA methylation with CRISPR-Cas9, which could prove invaluable for understanding and treating disorders that are linked to this epigenetic modification, such as cancer, lupus, muscular dystrophy, and many others.
Although these studies have been conducted in animal models and the only CRISPR-Cas9 research on non-viable human embryos was performed in China, there is much more to be learned about the effects of CRISPR in humans and how it might be used towards creating what has gained a lot of attention recently superior designer babies.
Continue to the next page to read about designer babies and future directions.
Follow this link:
Cut Out the Hype: Gene Editing With CRISPR and the Truth about Superhuman 'Designer Babies' - WhatIsEpigenetics.com (blog)
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