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HONG KONG - China"s Hong Kong Baptist University (HKBU) announced Thursday that its medicine scholars have succeeded in developing a novel targeted delivery system for CRISPR/Cas9 to achieve therapeutic genome editing of VEGFA in osteosarcoma (OS).

Their research paper, entitled "Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalised lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma", was recently published in the internationally renowned academic journal Biomaterials.

CRISPR/Cas9 is a budding genome editing technology which holds tremendous promise for cancer treatment. However, a major bottleneck for achieving the therapeutic potential of CRISPR/Cas9 is the lack of an in vivo targeted delivery system.

The HKBU team has achieved a breakthrough in the search for an answer to the crux of the above mentioned problem and developed an aptamer-functionalised delivery system for CRISPR/Cas9 with the treatment of OS as a research target.

The research team is led by Professor Lyu Aiping, dean of the School of Chinese Medicine (SCM) of HKBU, and Professor Zhang Ge, Director of Technology Development Division and Associate Director of Teaching and Research Division of SCM.

"OS, a very common primary malignant bone tumor in children and adolescents, is mainly treated by surgery and chemotherapy, but the five-year post-surgery survival rate is a mere 5 percent to 20 percent," Zhang said, "Aptamers which are single-stranded oligonucleotides and could specifically recognize target cells have been widely used for in vivo targeted delivery of therapeutics. VEGFA has been reported to be a novel therapeutic target for OS."

Lyu said,"The tumor-specific aptamers, when conjugated with PPC polymers encapsulating CRISPR/Cas9, may facilitate therapeutic genome editing in tumors."

In the experiments using a mouse model, the aptamer facilitated selective distribution of CRISPR/Cas9 in both orthotopic OS and lung metastasis, leading to effective in vivo VEGFA genome editing, inhibited orthotopic OS malignancy and lung metastasis, as well as reduced angiogenesis and bone lesion with no detectable toxicity. The research facilitated clinical application of CRISPR/Cas9 in tumor treatment.


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