New Genetic Engineering May Help Diabetes Patients with Obesity

CRISPR genetic engineering has many applications in the medical field and has revolutionized the world of genetic engineering in the last few years because it allows for very specific alteration in the DNA of human, plants and lower animal forms much faster than was previously possible.

What is CRISPR And How Does it Work

The acronym CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeat because it’s based on the organization of the DNA sequences found in the genomes of bacteria and other micro-organisms that are short and partially palindromic. In micro-organisms these short sequences are responsible for the destruction of invading viral organisms into their immune systems. The CRISPR system in the bacterial cells destroys the invading virus’ genome, this is an important distinction to make because the genome of the viral cells holds the genetic material that it needs to continue to replicate. So by destroying the genome the CRISPR system protects the bacteria from continued viral infection.

The system works in basically three steps, the first is adaptation. The CRISPR system in bacteria is made up of a series of short DNA sequences with short spacer sequences in between them. The spacers sequences are then transcribes into an RNA sequence which then guides the CRISPR system to matching DNA sequences. When that sequence is found then Cas9 an enzyme produced by the system, binds to the DNA and cuts it, destroying the foreign DNA.

Why the CRISPR System is Revolutionary

The CRISPR system is already being used effectively in many experimental therapies for other disease like cystic fibrosis, sickle cell anemia and leukemia. One of the reasons that researchers and geneticists prefer the CRISPR system for genetic engineering beyond its precision is because of the way it cuts DNA.

What makes the CRISPR system good for genetic engineering is the presence of the built in genetic editing tools. One being Cas9. Because Cas9 on its own can cut DNA acting like molecular scissors, unlike most other genetic engineering tools it doesn’t need to be paired with cleaving enzymes. It can also easily be matched with other readymade RNA sequences already at use in genetic research and can target multiple genes simultaneously.

Another facet of the CRISPR system is a second genetic editing tool that is even more precise than Cas9 and the difference is important. At the base both Cas9 and the other enzyme Cpf1 operate the same way, by cutting DNA. They can both be tailored with RNA sequences for greater precision, and do not need cleaving enzymes. But the Cas9 enzyme in its natural form it forms a complex with two smaller RNA sequences that is necessary for the cutting to be performed. Cpf1 complex is simpler in that it only needs one RNA sequence and is a smaller enzyme than Cas9.

The way that both enzymes cut DNA is also an important distinction. Cas9 cuts both strands of DNA in the same place, the result is even but blunt ends that reform with mutations. When Cpf1 cuts the strands it does in a manner where the strands are offset and there are overhangs on the ends of the strands, this can help with more precise insertion of new DNA. If the targeted DNA does become mutated, Cpf1 cuts far enough away from the recognition site which can allow for re-cutting and editing.

Applications in the Field of Diabetes and Obesity

Researchers at the University of Chicago have recently come up with a way to use genetically engineered skin grafts in targeting obesity and diabetes. They chose skin because it’s the most long lasting, inexpensive and safest form of organ transfer to the recipient body, but also because genetically engineered skin can be altered to match the recipient. The studies were done using wild type mice, specifically because unlike laboratory mutated mice they have a fully functional immune system that will register normal reaction to the skin grafts.

Using edited skin cells from newborn mice the researchers inserted a modified version of a glucagon-like peptide one, GLP1, a hormone that can help treat diabetes as it reduces the appetite and stimulates the release of insulin to lower blood sugar. Unfortunately GLP1 doesn’t last long in the blood stream and is difficult to administer orally.

After the mice had been induced with obesity and diabetes through their diets, they were then grafted with the genetically engineered skin The mice were then fed small amounts of antibiotic which induced them to produce a modified version of GPL1 that lasted three months where the mice showed lower glucose levels and higher insulin levels. Although trials on mice have yielded the type of successes that researchers were looking for, they are still a ways off from human testing to see just how well it will work.

Use and Applications

The CRISPR system has a very broad set of applications that are either at the moment being implemented or researched In industries for instance the use bacterial cultures CRISPR based immunity can be used to make the cultures more viral attack resistant, which will boost productivity. The original discovery of the CRISPR system was made in research at Danisco a food production company.

With use in labs researchers have learned how to make very precise changes to the genes of organisms from plants to animals. Because genes specific to their sequence, each sequence carries information that’s necessary in how to build and maintain an organism's cell structure. Even minute changes in gene sequences will alter the biology of a cell which can affect the health of an organism. Using CRISPR allows scientists to alter specific genes while not causing damage to others.

By far the most exciting part of CRISPR is what it will mean for the field of medicine, particularly for those that have genetic disorders. Using mice geneticists were able to correct a mutant gene that was responsible for a rare form of liver disease earlier this year (2017). Using the CRISPR system the mutated gene was replaced in adult mice with the correct gene sequence, the mice did not reject the new gene and the cure was obtained in one treatment.

In addition to genetic disorders the implications for other disease like the myriad of infectious ones in promising. Using the system in may be possible to create antibiotics that target only. disease causing bacterial strains, and a recent SITN Waves article discussed how it may be possible to make white blood cells resistant to the HIV virus.

The Implications of This new Research

CRISPR technology has relatively new and with any new technology there is a learning curve and a period of time before it’s fully understood and the system has been perfected. One way to do that is to make sure that the CRISPR RNA pairings are is specific to its target gene so that the CRISPR system doesn’t attack other genes. Vectors of delivery will also need to be researched and perfected before the system will be of any value to treating human diseases. But there has been enough excitement generated by this new technology that it has already spawned a number of biotech firms hoping to get in on the ground floor, and judging by the results so far, there doesn't seem to be an end to the good news that will come out of this technology.