The HENU-MQ Joint Center of Biomedical Innovation (JCBI) of School of Life Sciences published a research paper on CRISPR-Cas9 gene editing therapy for glioma in Science sub-journal (Science Advances), which is highlighted on the journal homepage.

CRISPR-Cas9 gene editing technology is considered to be one of the most important breakthroughs in biotechnology since the 21st century, and won the 2020 Nobel Prize in Chemistry. It can rapidly generate mutations, insertions and deletions in the target cell genome, thereby realizing DNA modification of the target genome. The founder of CRISPR technology and Nobel Prize winner Jennifer A. Doudna mentioned that "delivery may be the biggest bottleneck in somatic gene editing therapy". Therefore, the development of a safe and effective CRISPR delivery system is a necessary condition for gene editing in vivo therapy. This paper develops a safe CRISPR-Cas9 brain delivery system for refractory and relapse-prone malignant glioma (GBM), which transports CRISPR-Cas9 across the BBB to target brain diseased cells and efficiently edits oncogenes PLK1, enabling gene editing therapy for glioma. The platform meets the following design criteria: easy preparation, high loading, small size, long circulation, high penetration, strong targeting, fast release, high editing and low off-targeting, etc.. Cell and in vivo experiments verified that the nanocapsules had significantly enhanced BBB penetration, tumor tissue enrichment and retention capabilities in an orthotopic glioma tumor-bearing mouse model after intravenous injection, and the in vivo PLK1 editing efficiency was as high as 38.1%. However, off-target gene editing was negligible (less than 0.5%) in high-risk tissues (liver, kidney, and normal brain). More importantly the median survival time of tumor-bearing mice was significantly prolonged by nearly 3-fold after nanocapsule treatment. The CRISPR-Cas9 nanocapsules provide a delivery platform for brain diseases, including brain tumors, and are expected to achieve non-invasive, safe, and efficient gene therapy for brain diseases.

The result is published in Science Advancesas entitled "Blood-brain barrier-penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy". Henan University is the first affiliation of the paper. Associate Professor Yan Zou and graduate Xinhong Sun are the co-first authors, Professor Bingyang and Professor Meng Zheng are the co-corresponding authors. The research lasted for 4 years and received strong support from collaborators such as Academician Kam Leong from Columbia University, Professor Xingjie Liang from National Nano Center, Professor Jong Bea Park from National Cancer Center of Korea, Professor Wei Tao from Harvard Medical School and other collaborators. The research received supports from National Natural Science Foundation of China, National Key Research and Development Foundation on Nanometer Projects, and the scientific and technological innovation team and the talent support plan of Henan Province.

Paper link: https://www.science.org/doi/10.1126/sciadv.abm8011

The JCBI was established in 2015 by School of Life Sciences, Henan University, and was subsequently approved as Nano Biomedical International Joint Laboratory of Henan Province in 2016, Bio-Nano Medicine Disciplinary Innovation and Talent Introduction Base of Henan Province in 2018. In 2020, approved by Department of Science and Technology of Henan Province, it became a key laboratory of Henan Province.

The laboratory focuses on the mechanism research of brain diseases, the development of new diagnosis and treatment systems and the targeted therapy of brain diseases, as well as the screening of new therapeutic targets for brain diseases and research on the mechanism of delivery strategies (Nature Communications, 2020, 11, 2978；Advanced Science, 2021, 2102001)，development and application of brain diagnosis and treatment system (Advanced Materials, 2021, 202106082; Biomaterials, 2020, 229, 119576)，brain delivery system Construction (Advanced Materials, 2021, 2104779; Advanced Materials, 2019, 1903277; Advanced Materials, 2020, 2000416; Nano Letters, 2020, 20, 1637; Angew. Chem. Int. Ed. 2019, 58, 4938), preclinical evaluation and translation of brain-targeted nanomedicines (Science Advances, 2022, 8, eabm8011; Science Advances, 2020, 6, eabc7031; Advanced Materials, 2018, 1803717; ACS Nano, 2022, DOI: 10.1021/acsnano.2c00320), a series of research results have been achieved in these areas. Also being invited to write a number of reviews on brain bio-nano-drugs (Trends in Biotechnology, 2018, 36, 562；Advanced Science, 2020, 8, 2101090; Advanced Functional Materials, 2020, 2005029), it has produced a great academic influence in China and abroad.

JCBI insists on carrying out "Biology plus" interdisciplinary research around the HENU’s "First-Class Discipline" - biology, and promotes interdisciplinary integration of biology and related disciplines. Since 2016 the laboratory has hosted and undertaken more than 10 national-level scientific research projects such as National Key R&D Program for Youth Projects, National Overseas High-level Talent Youth Project, and National Natural Science Foundation of China. It has been awarded 16 Chinese invention patents and 5 international patents.

Resource: School of Life Sciences, HENU