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Glioblastoma: CRISPR nanocapsules used to target brain tumors in mice

Small capsules that provide CRISPR gene therapy to the brain can be used to target glioblastoma tumors


April 20, 2022

Glioblastoma brain cancer cells under a microscope

Shutterstock / Anna Durinikova

Nanocapsules, which deliver the gene-editing tool CRISPR to the brain, can be used to treat one of the most aggressive forms of brain cancer called glioblastoma. In tests on mouse models in this condition, the technique stopped tumor growth and extended lifespan.

CRISPR Is a tool for adding, removing, or altering genetic material in cells and has great potential for treating some conditions. It is more accurate and cheaper than other gene editing methods, but it is currently difficult to use in the brain.

Most methods that target the brain include injecting directly into brain tissue or inserting a CRISPR into a non-disease virus and then injecting it into the bloodstream. These methods have serious drawbacks, including potential damage to brain tissue and, in the case of viruses, the difficulty of identifying delivery. This increases the risk of serious side effects such as unintended gene mutations.

By packaging CRISPR in specially designed nanocapsules (small non-toxic polymer bubbles), researchers were able to address these problems elsewhere in the body, but the technique in the brain It was difficult to use. This is mainly due to the difficulty of crossing the blood-brain barrier. Blood vessels in the brain are less porous than elsewhere in the body and usually help protect them from harmful invaders.

“Brain disorders, including brain tumors, are particularly difficult to target therapeutically because of the blood-brain barrier,” says neurosurgeons. Dimitris Pracantona Kiss so New York University Grossman School of Medicine..

Well, Yanzo Henan-Macquarie University Biomedical Innovation Joint Center In China, a colleague has designed a new type of nanocapsule that can overcome this barrier and provide CRISPR therapy to mice with brain tumors.

In this example, the researcher uses CRISPR PLK1, It regulates the development of new cells and acts essentially overdrive in glioblastoma. In this study, tumor growth was stagnant in mice treated with single-tail injection, with a median survival of 68 days, compared to 24 days in controls receiving microcapsules containing non-targeted genetic material or saline. It was below. .. In addition, new techniques have caused very few (less than 0.5%) unwanted genetic mutations in tissues that are likely to occur.

Nanocapsules, which are only about 30 nanometers in size, are much smaller than many nanocapsules currently in use. Often in the range of 100-500 nanometers.. It also has an almost neutral charge. Positively charged nanoparticles are toxic to the body and are usually targeted and destroyed in the bloodstream.

“To our knowledge, our nanocapsules represent the most important non-invasive and non-viral strategies for effective and safe brain delivery. [glioblastoma] “Gene therapy,” Zou et al. Wrote: Paper published this week Science Advances..

“This is really exciting,” says Placantonakis. He says more tests are needed, but that’s a very encouraging first step. Researchers hope that this technique will also help treat brain conditions other than glioblastoma.

Journal reference: Science Advances, DOI: 10.1126 / sciadv.abm8011

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Glioblastoma: CRISPR nanocapsules used to target brain tumors in mice

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