Experimental Rice U. therapy could repair mutations that cause genetic diseases
A new technology that relies on a moth-infecting virus and nanomagnets could be used to edit defective genes that give rise to diseases like sickle cell, muscular dystrophy and cystic fibrosis.
Rice University bioengineer Gang Bao has combined magnetic nanoparticles with a viral container drawn from a particular species of moth to deliver CRISPR/Cas9 payloads that modify genes in a specific tissue or organ with spatial control.
Because magnetic fields are simple to manipulate and, unlike light, pass easily through tissue, Bao and his colleagues want to use them to control the expression of viral payloads in target tissues by activating the virus that is otherwise inactivated in blood.
The research appears in Nature Biomedical Engineering.
In nature, CRISPR/Cas9 bolsters microbes’ immune systems by recording the DNA of invaders. That gives microbes the ability to recognize and attack returning invaders, but scientists have been racing to adapt CRISPR/Cas9 to repair mutations that cause genetic diseases and to manipulate DNA in laboratory experiments.
CRISPR/Cas9 has the potential to halt hereditary disease – if scientists can get the genome-editing machinery to the right cells inside the body. But roadblocks remain, especially in delivering the gene-editing payloads with high efficiency.
Bao said it will be necessary to edit cells in the body to treat many diseases. “But efficiently delivering genome-editing machinery into target tissue in the body with spatial control remains a major challenge,” Bao said. “Even if you inject the viral vector locally, it can leak to other tissues and organs, and that could be dangerous.”
The delivery vehicle developed by Bao’s group is based on a virus that infects Autographa californica, aka the alfalfa looper, a moth native to North America. The cylindrical baculovirus vector (BV), the payload-carrying part of the virus, is considered large at up to 60 nanometers in diameter and 200-300 nanometers in length. That’s big enough to transport more than 38,000 base pairs of DNA, which is enough to supply multiple gene-editing units to a target cell, Bao said.
He said the inspiration to combine BV and magnetic nanoparticles came from discussions with Rice postdoctoral researcher and co-lead author Haibao Zhu, who learned about the virus during a postdoctoral stint in Singapore but knew nothing about magnetic nanoparticles until he joined the Bao lab. The Rice team had previous experience using iron oxide nanoparticles and an applied magnetic field to open blood vessel walls just enough to let large-molecule drugs pass through.
“We really didn’t know if this would work for gene editing or not, but we thought, ‘worth a shot,’” Bao said.
The researchers use the magnetic nanoparticles to activate BV and deliver gene-editing payloads only where they’re needed. To do this, they take advantage of an immune-system protein called C3 that normally inactivates baculoviruses.
“If we combine BV with magnetic nanoparticles, we can overcome this deactivation by applying the magnetic field,” Bao said. “The beauty is that when we deliver it, gene editing occurs only at the tissue, or the part of the tissue, where we apply the magnetic field.”
Application of the magnetic field allows BV transduction, the payload-delivery process that introduces gene-editing cargo into the target cell. The payload is also DNA, which encodes both a reporter gene and the CRISPR/Cas9 system.
In tests, the BV was loaded with green fluorescent proteins or firefly luciferase. Cells with the protein glowed brightly under a microscope, and experiments showed the magnets were highly effective at targeted delivery of BV cargoes in both cell cultures and lab animals.
Bao noted his and other labs are working on the delivery of CRISPR/Cas9 with adeno-associated viruses (AAV), but he said BV’s capacity for therapeutic cargo is roughly eight times larger. “However, it is necessary to make BV transductioninto target cells more efficient,” he said.
Learn more: Moths and magnets could save lives
The Latest on: Genetic diseases
via Google News
The Latest on: Genetic diseases
- Patients With Genetic Diseases Will Create Demand For Carrier Screening Market by 2031on December 8, 2021 at 9:00 pm
The latest Fact.MR study on global Carrier Screening market Survey presents an all in all compilation of the historical, current and future outlook of Carrier Screening Market Sale as well as the ...
- More diversity improves genetic research into cardiovascular disease, according to new studyon December 8, 2021 at 12:48 pm
A new study, co-led by Queen Mary University of London, has made the case for more diversity in genetic research.
- 'This is going to kill me': Rockton man with rare genetic disorder in need of 2 live donorson December 8, 2021 at 2:00 am
Joe Beard, a Rockton husband and father of two young girls, is in need of a new kidney, a new liver and a bone marrow transplant.
- Evenings with Genetics addresses genetic testing and heart diseaseon December 7, 2021 at 11:14 am
Can genetic testing shed light on your risk for cardiovascular disease? A Baylor College of Medicine cardiologist will address this question and more ...
- Study of Suicide Attempts Confirms Genetic Underpinnings Not Driven by Underlying Psychiatric Disorderson December 7, 2021 at 1:40 am
An international consortium of scientists dissects the shared genetic architecture of suicide attempts, psychiatric disorders, and non-psychiatric risk factors. In the largest genetic study of suicide ...
- Genetic variant linked to Amish community could pave way for new heart disease therapieson December 6, 2021 at 4:50 am
Researchers at the University of Maryland say a genetic variant linked to the Old Order Amish community in Pennsylvania reduce levels of LDL cholesterol and a blood-clotting protein. The findings ...
- Increasing emphasis on early disease detection and prevention is driving the growth of United States Genetic Testing Marketon December 6, 2021 at 12:11 am
The genetic testing is primarily a simple process in which our DNA is collected and pass through the bloodlines of all living beings is extracted and put under through inspection. Through this, change ...
- Genetic Testing Benefits Children With Unexplained Epilepsyon December 5, 2021 at 10:05 am
Genetic testing affected the medical care of nearly three of four children with unexplained epilepsy, a study of patients with infantile or childhood-onset seizures showed. A genetic diagnosis had a ...
- IVF used by some to avoid passing on genetic diseases to offspringon December 4, 2021 at 6:27 am
In vitro fertilization (IVF), widely known as a way to help infertile couples have babies, has taken on another remarkable use: It has become part of a procedure to help families keep from passing on ...
via Bing News