Biomedical engineers at Duke University successfully decreased blood cholesterol levels in mice through a new approach to gene-silencing technology.
Specifically, the engineers used a new delivery system of CRISPR/Cas9 into the bodies of mice. The new method resulted in reduced blood cholesterol levels in mice with the responsible gene rendered silent for the duration of six months — and this is only after a single treatment.
Additionally, through the new approach, the biomedical engineers were also able to observe how the immune systems of living organisms react when CRISPR/Cas9 was added to the bodies.
What Is CRISPR/Cas9?
Genome editing is the ability of different scientific technologies grouped together to alter a living organism's DNA. These technologies worked together to add, remove, alter genetic materials at certain locations in the genome.
Genome editing offers hope of treatment for otherwise irreversible diseases.
One approach to genome editing that has been developed is the CRISPR/Cas9. The term means "clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9."
CRISPR/Cas9 was derived from naturally occurring genome-editing system bacteria. The bacteria lock snippets of DNA from viruses and use them in its own creation of DNA segments or the CRISPR arrays.
These arrays allow the bacteria to recognize the viruses or similar variants of the viruses. The moment these viruses attack again, the bacteria will produce RNA segments from the arrays to attack back against the viruses. The bacteria will then utilize the Cas9 or a similar enzyme to stop the DNA apart, thereby disabling the viruses.
Reduced Blood Cholesterol Levels In Mice
Biomedical engineers at Duke University headed by Charles Gersbach developed a technique to successfully put together and deliver the CRISPR/Cas9 gene-silencing system to mice.
For the technique, the team used adeno-associated viral vectors to deliver CRISPR/Cas-9-based repressors to the mouse liver. AAV are small viruses that were engineered to target a variety of tissues during clinical trials that involved human gene therapy.
The said delivery system invalidated Pcsk9, a gene responsible for regulating cholesterol levels.
Several of the drugs developed to aid high cholesterol and cardiovascular disease work by blocking the activity of the Pcsk9 gene.
The new approach used by Gersbach and his team does not merely block but also ultimately stops the body from making the Pcsk9.
Immune System's Response Against Cas9
While they deliver the CRISPR/Cas-9 into the liver of the mouse, the scientists also observed that there is an immune response against the Cas9 protein. This means that the immune cells were infiltrating the liver the moment it became aware of the delivered Cas9.
The reaction gives the scientists a significant insight on how the immune system will respond to Cas9 gene technology therapy. Particularly significant is that the immune system might be recognizing Cas9 as a threat, and it is fighting the enzyme accordingly.
Their complete study is published in Nature Communications.