Understanding CRISPR Technology

• CRISPR is an immune system used by microbes to find and eliminate unwanted invaders.

CRISPR Definition

• CRISPR stands for “clustered interspaced short palindromic repeats.”
• It describes the genetic appearance of a system discovered in microbes as early as 1987.
• Around 2005, researchers discovered CRISPR is an immune system.
• Microbes use it to protect themselves from invading viruses.
• Microbes use CRISPR to recognize and eliminate specific trespassers.

How CRISPR Works

• When a virus or other invader enters a bacterial cell, the bacterium incorporates some of the trespasser’s DNA into its own genome.
• This allows it to find and eliminate the virus during future infections.
• When a virus infects a bacterial cell, CRISPR helps establish a genetic memory.
• The bacterium takes a piece of the virus’s genome and inserts the DNA into its own genome.
• From that newly acquired DNA sequence, CRISPR creates a new guide RNA.
• Guide RNA is a sequence that helps CRISPR find the invader via sequence complementarity.
• The next time the virus infects that bacteria cell, the guide RNA rapidly recognizes the virus DNA sequence, binds to it, and destroys it.

Gene and Cell Therapy

• Gene therapy involves using CRISPR as a macromolecule drug to either fix a mutated gene or regulate a defective gene to treat a disease.
• Cell therapy employs CRISPR to make your body’s cells attack toxic cells or regenerate beneficial cells.
• Gene therapy can mean fixing a mutated gene or regulating a gene’s expression into protein products.
• The challenge is managing therapy safely and cheaply.
• Cell therapy involves retrieving some of the patient’s T cells.
• Scientists engineer these cells as better fighters to recognize and eliminate tumorous cells.
• CRISPR enhances the efficacy and safety of these immune cells so that they are completely under control for the best clinical benefits.

Differences from Other Gene-Editing Tools

• CRISPR is much easier to program than other tools.
• Before CRISPR, most gene-editing tools were a single protein.
• To change the target, you need to completely redesign the protein’s sequence and then test if it even works, which is tedious, unpredictable, and time-consuming.
• CRISPR is elegant because the target recognition sequence is mostly encoded within an RNA rather than a protein.
• Redesigning this sequence is simple in molecular biology and reduces the burdens, cost, and timing.

Importance of CRISPR

• CRISPR can precisely modify a piece of DNA or its chemistry (epigenetics) in the human body.
• This makes it a potential tool for clinical uses in the biomedical sciences.
• CRISPR molecules have become highly promising as treatments because they allow us to precisely modify a piece of DNA in the human body.
• Recent FDA approval of the first CRISPR drug, Casgevy, in treating sickle cell anemia and beta thalassemia speaks to its safety and potential for other diseases.

Development Since Creation

• Scientists went from wondering if this technology would even work in human cells to getting the first CRISPR drug approved for clinical uses in about a decade.
• In the early days, CRISPR’s practical usefulness was not very publicly recognized.
• Jennifer Doudna and Emmanuelle Charpentier published their seminal 2012 paper on Cas9.
• Research and published papers grew exponentially.
• CRISPR is easy, flexible, and robust, and only takes a couple of weeks and a bit more than a few hundred dollars to set up now.
• Structural biologists solved the high-resolution, three-dimensional structure of what Cas9 and other CRISPR proteins look like.
• Bioinformaticians have revealed many new species of Cas molecules beyond Cas9, many of which have novel functions.
• Biochemists engineered CRISPR to understand how fast and tightly it binds to DNA.
• Bioengineers engineered the proteins to make them work more efficiently and more specifically.
• Clinical researchers started to use the tool to address particular diseases.
• The applications of CRISPR went beyond gene editing.

Future of CRISPR

• Future CRISPR drugs will address more incurable diseases.
• This provides a test case for CRISPR’s efficacy and safety in different organs and patients.
• Medicine isn't made in one day, different diseases are caused by different mechanisms.
• There are already more than dozens of CRISPR clinical trials for different diseases in the liver, immune cells, eyes, and muscles.
• CRISPR epigenetic editing is expanding the scope of disease to treat more types of muscular dystrophy, retina disorders, and brain diseases.

Nobel Prize

• Jennifer Doudna (University of California, Berkeley) and Emmanuelle Charpentier (Max Planck Unit for the Science of Pathogens) received the Nobel Prize in Chemistry.
• They received the Nobel Prize in Chemistry only seven years after CRISPR was first reported as a molecular system for modifying the human genome.
• Giving the Nobel Prize to CRISPR won’t give people the impression that the genome editing field is done.
• It is expanding its influence in plants, microbes, and difficult-to-engineer organisms such as fungi.

Other Real-World Applications

• Some other uses are diagnostics, manufacturing, sustainability, and ecological engineering.
• CRISPR has been developed as a way to sensitively detect pathogens in the environment that are affecting our bodies.
• There are also opportunities in manufacturing, such as making products that we care about using organisms like yeast and bacteria.
• Genome engineering may offer better manufacturing protocols through microbes that reduce greenhouse gases, plastic, and food waste.
• People are trying to eliminate certain invading or pathogenic mosquito species using CRISPR.
• Scientists have recently announced they were trying to revive a woolly mammoth that can live in the Arctic cold.

Ethical Concerns

• Some ethically questionable areas are disease prevention and eliminating pesky species, and some definite unethical areas are enhancement and creating designer babies.
• The division of treatment has three categories: cure, prevention, and enhancement.
• Curing someone’s disease is great.
• Prevention, which means someone is at risk of developing a problem, is a gray area.
• Enhancement is likely unethical.