Sunday , February 28 2021

New technologies based on cords and magnets could help to treat genetic diseases



New technologies based on gray infectious viruses and nanomagnets could be used to modify damaged genes that cause diseases such as sickle cell, muscular dystrophy and cystic fibrosis.

Rice University's bioengineer Gang Bao has combined magnetic nanoparticles with a virus container brought from a specific mother species to provide CRISPR / Cas9 workloads that modify genes in specific tissues or organs with spatial control.

Since magnetic fields are easy to manipulate and, unlike light, move easily through tissues, Bao and colleagues want to use them to control the expression of viral material in target tissues by activating a virus that is otherwise inactivated in the blood.

The study appears Natural Biomedical Engineering. In nature CRISPR / Cas9 intensifies the microbial immune system by registering an invader DNA. It gives microbes the ability to recognize and attack invading returns, but scientists are ready to adapt CRISPR / Cas9 to correct mutations that cause genetic diseases and manipulate DNA lab experiments.

CRISPR / Cas9 can withstand congenital diseases – if scientists can get a genome-editing machine in the right cells in the body. But there is still a roadblock, in particular, providing high-efficiency genes for editing the payload.

Bao said that in order to treat many diseases, it would be necessary to modify cells in the body. "But the effective delivery of genomic editing machines to target body tissues with spatial control remains a major challenge," Bao said. "Even if you inject a virus vector locally, it can leak into other tissues and organs and this can be dangerous."

The delivery tool developed by the Bao Group is based on the virus that infects Autographa californica, aka lucerne looper, a native of North America. The cylindrical baculovirus vector (BV), which is part of the viral load, is considered to be large with a diameter of 60 nanometers and a length of 200-300 nanometers. It's large enough to carry more than 38,000 base DNA pairs, which is enough to deliver multiple gene-edit units to the target cell, Bao said.

He said that the inspiration for combining BV and magnetic nanoparticles came from discussions with the Rice postdoctoral researcher and co-author Haibao Zhu who learned about the virus in post-processing in Singapore, but did not know about magnetic nanoparticles until he joined Bao's laboratory. The rice team had previous experience with the use of iron oxide nanoparticles and the applied magnetic field to open blood vessel walls that are large enough to allow macromolecular drugs to pass.

"We really did not know if it would work with genetic editing or not, but we thought it was a" worth a shot, "said Bao.

Researchers use magnetic nanoparticles to activate BVs and deliver useful gene load edits only when they are needed. To do this, they use immune system proteins such as C3, which usually deactivates baculoviruses.

"If we combine BV with magnetic nanoparticles, we can overcome this deactivation by applying a magnetic field," Bao said. "The beauty is that when it is delivered, the gene is edited only in the tissue or part of the tissue where we use the magnetic field."

The use of the magnetic field provides BV transduction, which is the cargo transfer process leading to a gene-modifying load in the target cell. The load capacity is also DNA that encodes both the reporter gene and the CRISPR / Cas9 system.

During the tests, BV was loaded with green fluorescent protein or luciferase lights. Experimental experiments showed that the magnets were highly effective in delivering BV crops to both cell cultures and laboratory animals in proteins that shine brightly on the microscope.

Bao noted that he and other laboratories are working on the delivery of CRISPR / Cas9 to adeno-related viruses (AAVs), but he claimed that the therapeutic volume of BV was about eight times higher. "However, it is necessary to make BV transduction in target cells more effective," he said.


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