Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours
| Autor: | Anthony T Chong, Hye Young Lee, Bumwhee Lee, Vladislav Bugay, Kunwoo Lee, Shree Panda, Niren Murthy, Robert Brenner, Hyo Min Park, Rodrigo Gonzales-Rojas |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Patch-Clamp Techniques Medicine (miscellaneous) Striatum Inbred C57BL Mice Fragile X Mental Retardation Protein 0302 clinical medicine Nanotechnology CRISPR Clustered Regularly Interspaced Short Palindromic Repeats Ribonucleoprotein Mice Knockout Neurons Behavior Animal Microglia Metabotropic glutamate receptor 5 Brain food and beverages Metabotropic Glutamate 5 Computer Science Applications Fragile X syndrome medicine.anatomical_structure Neurological Receptor Biotechnology Cell type Receptor Metabotropic Glutamate 5 Knockout Intellectual and Developmental Disabilities (IDD) Biomedical Engineering Bioengineering Article 03 medical and health sciences Rare Diseases Genetics medicine Animals Humans Behavior Animal business.industry fungi HEK 293 cells Neurosciences medicine.disease Corpus Striatum Brain Disorders Mice Inbred C57BL Disease Models Animal HEK293 Cells 030104 developmental biology Fragile X Syndrome Disease Models Nanoparticles Thy-1 Antigens Gold CRISPR-Cas Systems business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature biomedical engineering, vol 2, iss 7 |
| ISSN: | 2157-846X |
| Popis: | Technologies that can safely edit genes in the brains of adult animals may revolutionize the treatment of neurological diseases and the understanding of brain function. Here, we demonstrate that intracranial injection of CRISPR–Gold, a nonviral delivery vehicle for the CRISPR–Cas9 ribonucleoprotein, can edit genes in the brains of adult mice in multiple mouse models. CRISPR–Gold can deliver both Cas9 and Cpf1 ribonucleoproteins, and can edit all of the major cell types in the brain, including neurons, astrocytes and microglia, with undetectable levels of toxicity at the doses used. We also show that CRISPR–Gold designed to target the metabotropic glutamate receptor 5 (mGluR5) gene can efficiently reduce local mGluR5 levels in the striatum after an intracranial injection. The effect can also rescue mice from the exaggerated repetitive behaviours caused by fragile X syndrome, a common single-gene form of autism spectrum disorders. CRISPR–Gold may significantly accelerate the development of brain-targeted therapeutics and enable the rapid development of focal brain-knockout animal models. |
| Databáze: | OpenAIRE |
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