TB resistant cows: a promising future?

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IT WAS ANNOUNCED last month by Chinese scientists that a group of cows have been genetically engineered to be resistant to tuberculosis (TB), raising hopes of reducing the spread of the disease. TB is caused by a bacterium called Mycobacterium Tuberculosis and is one of the leading causes of death worldwide. It most commonly infects the lungs and is spread via water droplets when a patient coughs or sneezes.

Symptoms of TB include coughing up blood, fever and weight loss. In healthy individuals, infection by M. tuberculosis rarely causes any problems as their immune system can recognise and kill the bacteria. People who have compromised immune systems, such as those co-infected with HIV, are however particularly vulnerable. Once a person becomes infected they can remain symptom-free for years in a state known as latency and only go on to develop the active form of the disease if their immune system becomes weakened.

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TB is currently treatable, but the over-prescription and misuse of antibiotics has caused strains of the bacteria to evolve resistance. Scientists are therefore exploring novel ways to reduce the spread of the disease. One potential candidate for this is the genetic tool known as CRISPR, a fashionable and exciting technique that edits specific stretches of DNA. Standing for Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR (pronounced "crisper") are short, repetitive pieces of microbial DNA that are located close to genes known as Cas. Cas proteins are special enzymes that recognise the CRISPR sequences and cut them. The CRISPR/Cas system is used by bacteria as part of their immune system and its specificity is now being exploited by biologists to introduce precise changes to microbial DNA in order to study the effects. This can either be by deleting a gene to look at what happens if it is mutated or absent or by adding in a gene that may have come from a different organism.

The team of scientists have managed to use CRISPR to insert a gene associated with TB resistance into the genome of a cow. This gene encodes a protein called natural resistanceassociated macrophage protein-1 (NRAMP1) and has been linked previously to defence against the development of TB. By using CRISPR to introduce this gene to a selected target site, they were able to produce transgenic cattle that were more resistant to infection by a strain of Mycobacterium specific to cows, M. bovis. This is a huge advance in comparison to editing bacterial genomes; mammalian genetics is much more complex and the situation is muddied by ethic a l considerations involving the generation of genetically modified organisms (GMOs).

The scientists hope that the work they have done here might help progress the use of the CRISPR gene-editing technique in agricultural settings. Reducing the TB-associated mortality of cattle could save farmers money but this depends entirely on how cheaply the transgenic cows could be produced. It is likely to be met with some resistance by those opposed to GMOs and those who are concerned about if, or when, this technique may be considered in terms of human susceptibility to diseases like TB. Regardless of where you stand ethically, the science behind CRISPR is exciting, and its list of potential applications is still growing

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