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IMAGE: (From left) UCLA Dr. Steven Jonas, Jason Belling and Paul Weiss
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Credit: Reed Hutchinson / UCLA
A UCLA-led research team reports today that it has developed a new method of delivering DNA to stem cells and immune cells safely, quickly, and inexpensively. The method, described in the magazine. procedures of the National Academy of Sciences, could give scientists a new tool to manufacture gene therapies for people with cancer, genetic disorders, and blood diseases.
The study’s co-author is Paul Weiss, a distinguished professor of chemistry and biochemistry at UCLA, bioengineering, and materials science and engineering. “We are discovering how to introduce gene editing tools into cells efficiently, safely and economically,” he said. “We want to get them into large numbers of cells without using viruses, electro-shock treatments, or chemicals that will tear the membrane and kill many of the cells, and our results so far are promising.”
In current practice, cells used for gene therapy are sent to specialized laboratories, which can take up to two months to produce individualized treatment. And those treatments are expensive: a single regimen for a patient can cost hundreds of thousands of dollars.
“We hope that our method can be used in the future to prepare treatments that can be performed by the patient’s bed,” Weiss said.
The method could be used with CRISPR, the genetic engineering technique that allows DNA to be edited with remarkable precision. However, using CRISPR efficiently, safely and economically in medical therapies has proven to be a challenge, one that this new method can solve.
The technique uses high-frequency acoustic waves along with millions of cells that flow through an “acoustic fluid device” in a cell culture fluid. The device was invented by the research team as part of the study; Inside it are small speakers that convert electrical signals into mechanical vibrations that are used to manipulate cells.
That procedure opens the pores along the cell membranes that allow DNA and other biological charges to enter the cells, and allows researchers to insert the charge without the risk of damaging the cells by directly contacting them.
Dr. Steven Jonas, study co-author and UCLA clinical instructor in pediatrics, compared the ability of sound waves to move cells into experience when audience members actually feel the sound at a concert.
“In a concert hall, you can feel the bass, and if you can feel the sound, the cell can feel the sound wave,” said Jonas, a fellow at the California Institute of Nanosystems at UCLA, the UCLA Jonsson Comprehensive Cancer Center and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “We can design the acoustic waves to direct the cells as necessary.”
The researchers delivered short strands of DNA called plasmids to human blood cells and blood-forming stem cells that were specifically intended for laboratory research, and pumped millions of those cells through the acoustic device. Once inside a cell, a plasmid can become a missing or damaged protein, or it can give the cell new capabilities.
“When combined with new gene-editing approaches, the method allows us to correct a DNA sequence that is poorly encoded in a disease,” said Weiss, who is also a member of CNSI.
Plasmids used as templates for gene editing can make the correction because they have the correct encoded sequence for the desired protein, he explained.
Lead author Jason Belling, a UCLA graduate student in chemistry and biochemistry, was able to insert plasmids into the model cells used for the tests approximately 60% of the time, without using any chemical and physical treatments.
“Feasibility is very high compared to other techniques,” Weiss said, “but we still want higher efficiencies and are working to achieve it.”
Jonas, whose expertise is in treating childhood cancer and blood disorders, said the research has the potential to benefit adults and children with cancer, immune system disorders and genetic diseases.
“If labor works, and it seems it does, this research is an important step in bringing new therapies more broadly to patients who need them,” Jonas said. “Traditionally, we have treated cancers with chemotherapy, surgery, radiation, and bone marrow transplants. Now, we are in an incredible era of medicine, where we can use different types of gene therapy that can train the immune system to fight cancer.”
Jonas said that some existing treatments can take a patient’s T cells and tailor them with a gene that encodes a receptor that allows it to attack cancer.
“We want to be the delivery service that brings these therapeutic packages to the cells,” he said. “I want to treat my patients with cells designed this way.”
For the technique to lead to viable treatments for the disease, it would need to allow doctors to process at least a couple of hundred million cells, and in some cases billions of cells, safely, quickly, and cost-effectively for each patient.
The new approach is still under investigation and is not available to treat human patients.
The study’s other co-authors include Duke University professor Tony Huang, a pioneer in fluid acoustics and a UCLA student; Dr. Stephen Young, Distinguished Professor of Medicine and Human Genetics at UCLA’s David Geffen School of Medicine; and Dr. Satiro De Oliveira, assistant professor of pediatrics at UCLA.
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The study was funded in part through the Director of the National Institutes of Health’s Jonas Early Independence Award; the University of California Accelerated Innovation Center; and Belling’s predoctoral fellowship through the National Heart, Lung, and Blood Institute. Jonas also received awards for young researchers from the Alex’s Lemonade Stand for Children’s Cancer Research, the Hyundai Hope on Wheels Foundation for Pediatric Cancer Research, and the Tower Cancer Research Foundation. The UCLA Technology Development Group Innovation Fund also provided funds.
The Weiss research group has applied for patents on the fluid acoustic device and related devices, in collaboration with the Technology Development Group.
