A few months ago, scientists at the Salk Institute led by Professor Juan Carlos Izpisua Belmonte announced that for the first time ever, they managed to successfully insert DNA at a specific location. Following that targeted insertion, they were able to partially restore vision in their test subjects — blind rodents. And that discovery opened the floodgates for the development of new treatments for heart, neurological and retinal diseases.
So what makes this novel technology crucial? Current DNA editing techniques only work on cells that can still divide. This is the first time that DNA modification was done on cells that are no longer capable of dividing. Examples of such cells are those that can be found in the heart, the brain and the eyes, which is why the discovery is relevant to diseases related to these specific organs.
To accomplish what they did, the Salk scientists focused on a cellular pathway called NHEJ (non-homologous end-joining) which repairs DNA breaks by reuniting (or rejoining) original strand ends. By integrating this process with gene-editing technique CRISPR-Cas9, they were able to insert modified DNA at precise spots in non-dividing cells. Specifically, the team concocted their own nucleic acid cocktail (which they called homology-independent targeted integration or HITI), then used an inert virus to deliver it to the target cells, in this case, neurons from human embryonic stem cells.
After showing that targeted delivery of DNA cells is possible — they were able to deliver their cocktail to the brains of adult mice — they went a step further. They tested the technique on rats afflicted with retinitis pigmentosa, a hereditary form of retinal degradation that causes blindness in humans. They used HITI to deliver a functional copy of Mertk (one of the genes that get damaged as a result of retinitis pigmentosa) to the eyes of 3-week old ‘blind’ rodents. After 5 weeks, they checked on the rats and discovered promising results — not only did the subjects show responsiveness to light, they also passed a number of tests which indicated that their retinal cells have healed.
As Professor Belmonte said in a statement: “We now have a technology that allows us to modify the DNA of non-dividing cells, to fix broken genes in the brain, heart and liver. It allows us for the first time to be able to dream of curing diseases that we couldn’t before, which is exciting.”
Almost five months since that breakthrough was first announced, we’re hoping that more progress has been made by the team and that we’ll be hearing more good news soon.
Details of the findings are available online through the journal Nature Reviews under the title “NHEJ and CRISPR–Cas9 improve gene therapy”.