Since the past few years, the term “CRISPR” or “CRISPR Cas9” is continually being thrown around, among various scientific and non-scientific communities. Also, the chances are that you have also come across this term while surfing the internet or scrolling down your social media account.
Moreover, you might also watch last year sci-fi movie “the Rampage” that is about using CRISPR technology to transforms animals like Gorilla into a flying dragon-monster. Also, it got popularity in public after featured in HBO show (Last Week Tonight With John Oliver).
In short, CRISPR is currently the hottest scientific breakthrough and is considered as the Taylor Swift of Science.
However, CRISPR is quite well explained by Nuclineers.com. Here, let me tell you why it is such a huge sensation and their real-life applications.
What the Heck is CRISPR?
CRISPR stands for clustered regularly interspaced or interspersed short palindromic repeats. It is a new gene-editing tool that allows researchers to more precisely than ever before editor modifies the genome of almost any organism. The tool is making gene-editing efficient, accurate, and fast than ever.
How CRISPR Works?
Naturally, it works by utilizing a bacterial adaptive defense system against invaders like bacteriophages. Whenever bacteria are invaded, the CRISPR system kicks in and start searching for a specific sequence in a viral genome known as PAM (protospacer adjacent motifs). After recognition, the CAS protein (CRISPR associated proteins) cleave the foreign DNA. Later, bacteria then integrate these pieces into its genome in a location called CRISPR locus. By this bacteria gains immunity against that specific foreign entity
Today, CRISPR applications go beyond healthcare, and it already transformed many areas of biology. I gathered some of the most notable achievement so far;
CRISPR for Diseases Treatment
CRISPR based gene therapy promise to revolutionize the medicines, including the treatment of genetic disorders. The diseases that once were considered unsolvable and incurable. And there are even some breakthroughs by using CRISPR on some of the following conditions.
Cancer could be one of the primary targets for CRISPR as it occurs when there is a mutation in some specific genes. The CRISPR tool could be designed in a manner that will only target and correct mutated genes. And hence restore their normal function.
Currently, the CRISPR clinical trials are carried out in Hangzhou Cancer Hospital, China, where scientists utilize CRISPR approach to knock out the PD-1 receptors gene from the tumor cells in esophagus cancer. These genetically altered tumor cells are then reinfused into patient bloodstream. Hence, to enhance the T cells anti-tumor activity.
PD-1 protein expressed on the surface of both lung and esophageal tumor cells. It instructs the body’s natural immune system (T-cells) not to attack.
CRISPR mediated therapies to knocking out PD-1 is an ideal way to treat other cancer types too. Dr. Edward Stadtmauer from the University of Pennsylvania leads the first CRISPR clinical trials in the US. Their team follows the same approach to treat multiple myeloma, melanoma, synovial sarcoma, and myxoid/round cell liposarcoma.
CRISPR technology also renewed hope as a possible alternative strategy to remove HIV from infected cells. It could be utilized in several ways either by targeting the viral DNA inside the infected cells or by making the cells resistant to HIV.
One of the greatest triumphs so far achieved by the researchers at the Temple University of Philadelphia to successfully eradicate HIV-1 from the infected Immune cells (T-cells).
Another group of Researchers from the Kobe University in Japan used CRISPR/Cas9 and successfully eliminated regulatory genes, i.e., Tat and Rev of HIV-1. Thus, the virus no longer replicates and increase their number.
Tickle Antibiotics-Resistant Bugs
Researches developed CRISPR mediated therapies to kill antibiotics resistant bugs, thus, bypassing the need for antibiotics.
Recently, Scientists used a CRISPR variant called CRISPR Interference (CRISPRi) to interact and block the antibiotics interference genes of bacteria, and thus, make them sensitive to it.
In 2015, Udi Qimron of Tel Aviv University used CRISPR along with probiotics using bacteriophage is a delivery system, and thus, sensitize antibiotics resistance bugs to the drugs.
Making Diseases Self-Destruct
The University of Wisconsin, Madison researcher team under the supervision of Jan Peter Van Pijkeren developed a CRISPR-based probiotic to make antibiotic resistant bacteria self-destructive.
Moreover, CRISPR could also cure diseases like Down’s Syndrome, Sickle Cell Diseases, Cystic Fibrosis, Duchenne Muscular Dystrophy, and more!
Stop or Reverse Aging
Now, scientists are also trying to stop or reverse aging and other age-related neurodegenerative diseases using CRISPR technology.
Currently, a CRISPR pioneer and Harvard Geneticist Dr. George Church follow CRISPR approach to slow or reverse aging.
Moreover, researchers from the University of Alabama, Birmingham, reversed skin wrinkle, and hair loss in a mice model.
Recently, Salk Institute researchers developed a unique CRISPR/Cas9 mediated therapy to suppress the mechanism of aging in mice with Hutchinson-Gilford progeria syndrome.
In theory, CRISPR could also be used to modify not just a single organism but an entire species – the concept called ‘Gene Drive.’ It involves the inherited of only desirable genes in a population and would lead to new speciation.
Currently, CRISPR is used in gene drive against malaria by targeting a ‘doublesex’ gene in Anopheles mosquitoes. When mutated in females will no longer lay eggs and suck blood, thus, prevents the spreading of malaria.
Because of extensive inbreeding, various pets became susceptible to numerous fatal genetic disorders. Pet lovers are always interested in taking advantage of the latest technologies to test health and breed. Now, researches are passionate and have a plan to treat and improve them using the CRISPR gene-editing technology.
A fabulous example is Dalmatians, which often carry inherited disease, hyperuricemia, because of the genetic mutation that prone them to suffer from bladder stones. In the US, a dog breeder, David Ishee, is hoping to use CRISPR and repair a single letter mutation in their genome. However, the animals should be the first review by the FDA before they can be sold.
Moreover, using CRISPR technology researches from the University of Texas Southwestern Medical Center, treated dogs having Duchenne muscular dystrophy. “[The dogs] showed obvious signs of behavioral improvement – running, jumping – it was quite dramatic,” said lead researcher Eric Olson.
Other projects include the creation of miniature pigs as a pet sold by Chinese Institute. And koi carps with custom size, color, and patterns.
CRISPR – a future of drug discovery
The development of safe and effective drugs is notoriously long and costly; thus, make it a risky endeavor for pharmaceutical companies. Moreover, only a few make it to the real market. Therefore, technologies like CRISPR-Cas plays a big part to overcome these barriers and expand drug discovery.
“This type of gene editing [CRISPR] is ready to have an immediate impact in real-world drug discovery and development” emphatically concluded by CRISPR pioneer and co-discoverer Jennifer Doudna.
The drug discovery stages mostly depend on the manipulation of genomes; deliberately inhibitor active expression of genes to determine diseases targets (protein or gene) that causes or prevent the diseases. Therefore, identifying targets for the development of potential drugs and to test their therapeutic efficacy.
However, the current approaches to manipulate genomes are limited by speed, accuracy, and cost-effective. Meanwhile, CRISPR is the most accurate, efficient, and cheapest gene editing tool and could be used to create cellular and even whole animal model system to mimic disease. Thus, it allows researchers to verify drug safety and efficacy more accurately within less time.
Biofuels is an emerging industry that aims to produce bio-based fuels, minimizing our dependency on natural sources and in turn, reducing the harmful effects of naturally occurring fuels on nature.
Organisms and primary algae can produce bio-based fuels. However, it did not deliver at a high level to make it economically viable. Therefore, CRISPR is the best candidate to create modifications in the microbe’s genomes to increase their production efficiency.
The partnership between synthetic Genomics of J. Craig Venter and oil company Exxon Mobil aims to use CRISPR technology to create strains of algae for oil improvement. After eight years of research, the joint company twice the production of fuels. Moreover, their target is to produce 10,000 barrels of algae biofuels each day in 2025.
Other projects include the knocking out of specific genes of green algae species such as Chlamydomonas reinhardtii to produce a high amount of biodiesel. While disrupting some essential genes in Rhodosporidium toruloides, a fungal species, researchers enabled it to be used on an industrial level for the production of bio-based fuels.
DNA Tape Recorders
Today, data are dramatically increasing, and soon we are getting out of ways to hold and store it. Moreover, it also required a massive space for storage. Therefore, there is a need for an alternative approach, and DNA is considered as a suitable candidate for it. Also, DNA can withstand harsh conditions and can easily be replicated.
It has been estimated that a single gram of DNA can store petabytes of data. Nick Goldman and his colleagues from the European bioinformatics institute, showed for the first that how DNA can be harnessed as the storage material. They successfully stored Shakespeare sonnets, 26-second audio clip of Martin king Luther speech, “I have a dream.” Also, the famous paper of Watson and Crick about the structure of DNA, a photo of the researcher’s institute and a file describing how this data was converted. The information was about 739 kilobytes in size.
Harvard scientists followed CRISPR approach to develop a creative molecular tool – CAMERA short for CRISPR-mediated analog multi-event recording apparatus (a mouthful!). The CAMERA act as recorder of events in the lifetime of a cell, such as exposure to antibiotics, nutrients, viruses, and light.
However, to achieve this, the team first programmed CRISPR into a bacterial cell and particularly “guided RNA” so it can only kick into action in the presence of the signal; let say, an antibiotic or viral attack. Once encountered, the gRNA direct Cas9 (CRISPR scissors) to the target, thus, cut it into pieces. If no invasion, no guide RNA, no Cas9 and no chopping takes place.
De-extinction of Animals
Even it may sound radical and science fictional, but scientists are planning to bring back extinct animals using CRISPR technology.
George Church of Harvard University was in the spotlight when he revealed his plans to bring the woolly mammoth back. By genetically combine the endangered Indian elephant genes with the fossil recovered genes of mammoth, Thus, to create a hybrid embryo. Furthermore, they also create an artificial womb because implanting such editing embryos in an endangered animal would be unethical.
Moreover, another research team led by Ben Novak at the University of California is trying to bring back passenger pigeons. Once a common bird of North American forests. Following the CRISPR approach, the team plan to insert fossil recovered genes of passenger pigeons into its current relative — the band tail pigeon.
On a positive note, if this de-extinction worked. We may be able to save endangered animals from getting extinct.
Modifying human embryos for healthier babies
This is one of the most controversial and hotly debated as the perception regarding healthier babies is very vague. Some consider it free from genetic diseases, while others take it as a term of designer babies. However, with current technologies, it is challenging to create designer babies, as we do not have enough knowledge about the regulation of genes we target plus the effect of epigenetics. While editing embryos to make them free from genetic diseases and resistant to them is possible.
In 2016, a Swedish research team under the supervision of Fredrick Lanner used CRISPR to make modifications in healthy human embryos. For the hope that the gene editing within human embryos will lead to improving/treat infertility and prevent miscarriage.
In November 2018, He Jiankui of Southern University of Science and Technology, China, claimed that he successfully created first ever CRISPR edited embryos. That later lead to twin girls, he named them lulu and nana and are HIV-1 resistant.
Hopefully, soon, scientists may be able to edit embryos to correct disease-causing mutations. While before that, we need to study more about CRISPR off-target variations, gene interactions, and effects of epigenetics. These all are some of the factors that help in differential gene expressions.
CRISPR has already disrupted many industries, including healthcare, by treating diseases like Cancer, HIV, Down’s Syndrome, and more. Moreover, outside healthcare, it has an impact on agriculture, FoodTech, and sustainable energy. Even though its potential is outstanding, but if left unregulated/ unchecked, it will soon become an agent of Chaos.