Scientists have improved upon a form of gene-editing therapy, creating an experimental treatment that looks to hold great promise for treating high cholesterol – a diagnosis affecting tens of millions of Americans, and linked to a number serious health complications.

In new research conducted with mice, researchers used an injection of a newly-formulated lipid nanoparticle to deliver CRISPR-Cas9 genome editing components to living animals, with a single shot of the treatment reducing levels of low-density lipoprotein (LDL) cholesterol by up to 56.8 percent.

In contrast, an existing FDA-approved lipid nanoparticle (or LNP; a tiny, biodegradable fat capsule) delivery system could only manage to reduce LDLs by 15.7 percent in testing.

Of course, these results have so far only been demonstrated in mice, so the new therapy will take a lot of further testing before we know it's both safe and equally effective in humans. But based on these results so far, signs are promising.

The way the treatment works relates to a gene in humans called Angiopoietin-like 3 (Angptl3), which produces proteins that inhibit the breakdown of certain fats in the bloodstream.

People with a mutation in this gene tend to have lower amounts of fatty triglycerides and cholesterol in their blood – without showing other kinds of health complications – and for years scientists have been trying to recreate the process, with treatments that effectively mimic the effects of the mutation.

"If we can replicate that condition by knocking out the Angptl3 gene in others, we have a good chance of having a safe and long term solution to high cholesterol," says biomedical engineer Qiaobing Xu from Tufts University.

"We just have to make sure we deliver the gene editing package specifically to the liver so as not to create unwanted side effects."

In the new research, Xu's team developed a new formulation of LNPs called 306-O12B to target the gene, producing therapeutic effects in wild-type C57BL/6 mice that lasted at stable levels for 100 days after just a single injection of the treatment.

In addition to the cholesterol reduction, the experiment produced a 29.4 percent decrease in triglycerides in the animals' blood, whereas the FDA-approved delivery method showed only a 16.3 percent reduction.

The work built upon findings published a couple of years ago, when Xu's lab figured out new ways to tweak the efficiency of targeted genomic editing via LNPs, thanks to optimizations provided by a tail-branched molecular structure of the lipids.

By packing the LNP envelopes with strands of engineered messenger RNA (mRNA) and single guide RNA (sgRNA) targeting the Angptl3 gene, the researchers could use CRISPR technology to knock the gene out. In turn, this reduces production of the Angptl3 protein by about two-thirds (65.2 percent), which helps the body to break down fats before they build up in the bloodstream.

"Importantly, no evidence of off-target mutagenesis at nine top-predicted sites was observed nor any apparent liver toxicity," the researchers explain in their paper.

"The system we established here offers a clinically viable approach for liver-specific delivery of CRISPR-Cas9–based genome editing tools."

The team suggests that the efficiency of the knockdown treatment in humans would likely be about the same as it is in mice, with the effects of the therapy potentially lasting up to a year (not that their own results demonstrate that yet), due to slow turnover of cells in the liver.

Until we know more about how 306-O12B might act in human bodies, this formulation of cholesterol-lowering medication won't be available in your local pharmacy.

But with subsequent testing, it's a possibility one day, the researchers think.

"Outcomes of this study may advance the systemic delivery of CRISPR genome editing machinery in the clinic," the authors explain.

"To realize the final clinical application, more detailed preclinical studies for the chronic tolerability, off-target effects, and the efficacy in large animals should be performed in the future."

The findings are reported in PNAS.