Gene Editing Therapies in Living Patients

The most interesting life and health sciences news released last week describe preliminary advances toward in-vivo gene editing. The first patient has received a gene editing treatment in a clinical trial of a new in-vivo gene therapy developed by biotechnology company Sangamo Therapeutics. Meanwhile, MIT researchers have packaged CRISPR gene therapy components in nanoparticles, eliminating the need to use viruses for delivery and successfully “reprogramming the liver” in laboratory mice.

"The infusion takes place for anywhere from two to three hours. And that's it," said Dr. Edward Conner, senior vice president and chief medical officer of Sangamo Therapeutics, as reported by CNN. "We're very hopeful." Conner explained that Sangamo’s zinc finger nuclease (ZFN) gene editor is delivered by a non-replicating, non-pathogenic virus, commonly used by gene therapy scientists.

“What’s really exciting here is that we’ve shown you can make a nanoparticle that can be used to permanently and specifically edit the DNA in the liver of an adult animal,” said lead MIT researcher Daniel Anderson. “I think having a fully synthetic nanoparticle that can specifically turn genes off could be a powerful tool not just for Pcsk9 but for other diseases as well. The liver is a really important organ and also is a source of disease for many people. If you can reprogram the DNA of your liver while you’re still using it, we think there are many diseases that could be addressed.”

Other top headlines cover surgeon Sergio Canavero’s controversial plans to perform the first human head transplant real soon, but most reactions are skeptical.

First clinical trial patient treated with in-vivo gene editing. Biotechnology company Sangamo Therapeutics announced the treatment of the first patient in a clinical trial to evaluate SB-913, an investigational in-vivo genome editing therapy for people with mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. SB-913 uses Sangamo's zinc finger nuclease (ZFN) genome editing technology to insert a corrective gene into a precise location in the DNA of liver cells, as described in a 2015 research paper published in Blood. Sangamo aims use SB-913 to treat MPS II, with the goal of enabling a patient's liver to produce a lifelong and stable supply of an enzyme he or she currently lacks.

Nanoparticles deliver CRISPR gene editing payloads to live laboratory mice. Scientists at MIT have developed nanoparticles that can deliver full CRISPR DNA-editing payloads, eliminating the need to use viruses for delivery.  A study published in Nature Biotechnology shows that, using the new packaging and delivery technique, the researchers were able to cut out certain genes, including a gene known as Pcsk9 and associated with high cholesterol levels, in about 80 percent of the liver cells of adult laboratory mice, and achieve a 35-40 percent reduction of cholesterol level, the best success rate ever achieved with CRISPR in adult animals.

Watching nanoscale chemistry in motion with electron microscopy. Researchers at Northwestern University have captured on video organic nanoparticles colliding and fusing together. The research results, published in Journal of the American Chemical Society, demonstrate the ability of an emerging imaging technique, called “Liquid-Cell Transmission Electron Microscopy,” to watch and record dynamic phenomena in organic materials systems on the nanoscale. According to the scientists, the new imaging technique will help studying the interaction of synthetic materials with biological systems, and developing new drug delivery methods.

Ultrasound bioprobe permits imaging subcellular structures inside living cells. In related news, scientists at Northwestern University have developed a non-invasive approach that permits viewing subcellular structures and their mechanical behavior at nanoscale resolution, inside living cells. A study published in Science Advances describes a technique, dubbed Ultrasound Bioprobe, which combines ultrasound waves with atomic force microscopy, interacting with live cells to determine the changes in their mechanical behavior. The researchers are persuaded that the ability to monitor real-time imaging of the nanomechanical changes in complex biological systems could open the door to early diagnostics and new therapeutic strategies.

Trimming unwanted proteins away from cells. Researchers at Max Planck Institute for Biophysical Chemistry have developed a new method to directly and rapidly destroy any protein in any kind of cell. Dubbed Trim-Away, the new method is simpler and faster than CRISPR gene editing and RNA interference. The research results, published in Cell, show that Trim-Away is very simple to use, removes proteins within minutes, and is able to distinguish between different variants of a protein. While warning that a therapeutic application is still far-off, the scientists are persuaded that this research could one day result in new therapies.