Salk researchers have discovered, for the first time, how to place DNA in specific locations in non-dividing cells
Salk Institute researchers have discovered a holy grail of gene editing—the ability to, for the first time, insert DNA at a target location into the non-dividing cells that make up the majority of adult organs and tissues. The technique, which the team showed was able to partially restore visual responses in blind rodents, will open new avenues for basic research and a variety of treatments, such as for retinal, heart and neurological diseases.
“We are very excited by the technology we discovered because it’s something that could not be done before,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and senior author of the paper published on November 16, 2016 in Nature. “For the first time, we can enter into cells that do not divide and modify the DNA at will. The possible applications of this discovery are vast.”
Until now, techniques that modify DNA—such as the CRISPR-Cas9 system—have been most effective in dividing cells, such as those in skin or the gut, using the cells’ normal copying mechanisms. The new Salk technology is ten times more efficient than other methods at incorporating new DNA into cultures of dividing cells, making it a promising tool for both research and medicine. But, more importantly, the Salk technique represents the first time scientists have managed to insert a new gene into a precise DNA location in adult cells that no longer divide, such as those of the eye, brain, pancreas or heart, offering new possibilities for therapeutic applications in these cells.
To achieve this, the Salk researchers targeted a DNA-repair cellular pathway called NHEJ (for “non-homologous end-joining”), which repairs routine DNA breaks by rejoining the original strand ends. They paired this process with existing gene-editing technology to successfully place new DNA into a precise location in non-dividing cells.
“Using this NHEJ pathway to insert entirely new DNA is revolutionary for editing the genome in live adult organisms,” says Keiichiro Suzuki, a senior research associate in the Izpisua Belmonte lab and one of the paper’s lead authors. “No one has done this before.”
First, the Salk team worked on optimizing the NHEJ machinery for use with the CRISPR-Cas9 system, which allows DNA to be inserted at very precise locations within the genome. The team created a custom insertion package made up of a nucleic acid cocktail, which they call HITI, or homology-independent targeted integration. Then they used an inert virus to deliver HITI’s package of genetic instructions to neurons derived from human embryonic stem cells.
“That was the first indication that HITI might work in non-dividing cells,” says Jun Wu, staff scientist and co-lead author. With that feat under their belts, the team then successfully delivered the construct to the brains of adult mice. Finally, to explore the possibility of using HITI for gene-replacement therapy, the team tested the technique on a rat model for retinitis pigmentosa, an inherited retinal degeneration condition that causes blindness in humans. This time, the team used HITI to deliver to the eyes of 3-week-old rats a functional copy of Mertk, one of the genes that is damaged in retinitis pigmentosa. Analysis performed when the rats were 8 weeks old showed that the animals were able to respond to light, and passed several tests indicating healing in their retinal cells.
“We were able to improve the vision of these blind rats,” says co-lead author Reyna Hernandez-Benitez, a Salk research associate. “This early success suggests that this technology is very promising.”
The team’s next steps will be to improve the delivery efficiency of the HITI construct. As with all genome editing technologies, getting enough cells to incorporate the new DNA is a challenge. The beauty of HITI technology is that it is adaptable to any targeted genome engineering system, not just CRISPR-Cas9. Thus, as the safety and efficiency of these systems improve, so too will the usefulness of HITI.
“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,” says Izpisua Belmonte. “It allows us for the first time to be able to dream of curing diseases that we couldn’t before, which is exciting.”
The Latest on: Gene editing
via Google News
The Latest on: Gene editing
- Book review: 'Pandemic' rings warning bell about gene-editing technology on December 16, 2018 at 3:27 am
When there's a scientific breakthrough, Robin Cook doesn't just stand up and cheer. He uses his fertile imagination and writes a novel about its possible perils. In his latest medical thriller, "Pande... […]
- Tom Steiger: Problems abound in Chinese gene-editing research on December 15, 2018 at 7:53 pm
On Nov 26 Dr. He Jankui, a Chinese biomedical researcher, became (in)famous. He shocked the world by announcing that he had used a gene splicing technology to edit the genes of two embryos, who he cla... […]
- Cibus IPO: Gene-Editing Technology And Very Risky on December 14, 2018 at 1:00 pm
Cibus Ltd. is a biotechnology company developing plant traits for the global seed industry with advanced technologies. The company’s most relevant system is its highly differentiated gene ... […]
- Gene Tweaking Prevented Obesity in Mice on December 14, 2018 at 9:37 am
FRIDAY, Dec. 14, 2018 (HealthDay News) -- A modified version of the CRISPR gene-editing technique could help fight obesity without having to alter any genes, a new study in mice suggests. CRISPR, an a... […]
- Follow These Simple Rules For Precise CRISPR Gene Editing on December 14, 2018 at 6:29 am
CRISPR/Cas9 gene editing in human cells is not an exact science—yet. Most cases of its use so far are fairly experimental; scientists can’t always predict precisely how DNA will be modified. Maybe the... […]
- CRISPR gene therapy regulates hunger, staves off severe obesity in mice on December 14, 2018 at 3:42 am
CRISPR gene editing technologies offer some exciting possibilities for medicine, whether it’s helping to treat ALS, battling the spread of malaria, or potentially providing us with a limitless supply ... […]
- Bloomberg Opinion: The science of gene editing demands caution and consensus on December 13, 2018 at 11:25 pm
The following editorial appears on Bloomberg Opinion. A Chinese scientist’s claim to have edited the genes of human embryos has provoked condemnation from scientists worldwide, and rightly so. He Jian... […]
- Using CRISPR gene editing, researchers develop self-cloning hybrid rice on December 13, 2018 at 9:06 pm
After decades of efforts, scientists have managed to modify a hybrid rice strain so that it passes on its favorable traits in its own seeds, according to ScienceDaily. By producing clones from its see... […]
- Scientists Say Gene-Edited Babies Claim Is 'Wake-Up Call' For World on December 13, 2018 at 11:09 am
Some scientists welcomed the statement from the academies as another important step to rein in dangers posed by powerful new gene-editing techniques without hindering their potential to prevent suffer... […]
via Bing News