Introducing a protective mutation that lowers cholesterol levels could cut rates of cardiovascular disease
It's known that a number of mutations can increase likelihood of cardiovascular disease and atherosclerosis, but we've also discovered that certain mutations can protect against these too. In 2005 researchers revealed that a knock out mutation in the PCSK9 gene produces naturally low cholesterol levels - resulting in lower rates of CVD and no observable side effects. PCSK9 is involved with degrading another key protein that deals with intake of circulating LDL (low density lipoprotein), the primary carrier of cholesterol in the blood. A lack of PCSK9 therefore upregulates this process and reduces LDL levels.
Testing a gene editing approach
Antibody drugs have already been developed that target PCSK9, with results due to be released in March. These are expensive however and must be constantly reapplied, which makes them somewhat crude in comparison to a gene editing approach, which resolves the issue at its source. A team at AstraZeneca have taken the approach to the next level and used a CRISPR strategy to block PCSK9 expression in mice. The result of this experiment was that cholesterol levels dropped even further than after antibody application. What's more, the gene used was a human variant, which bodes well for blocking the same gene in humans.
While CRISPR technology is still in its early days right now, there are many teams working on creating safer versions with less off-target effects; making it more accurate and less likely to edit a wrong sequence of DNA. This experiment directly edited the DNA, but a safer alternative could be to simply edit the epigenome and silence expression without actually tampering with the sequence itself. It remains to be seen exactly how effective this might be against CVD, but it's certainly an exciting strategy that deserves further study. Considering CVD killed around 17.5 million people in 2012 alone, an efficacious preventative intervention could massively reduce spending and mortality rates.
Read more at New Scientist