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Technique developed to selectively target cancer cells with CRISPR/Cas9

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In a paper recently published in Biomaterials, a group from Hong Kong, led by Ge Zang, Group Leader at the School of Chinese Medicine (Hong Kong Baptist University, ), attached CRISPR/Cas9 complexes to aptamers, long-single strands of DNA with a specific code. The team used these aptamers to bind to DNA found in osteosarcomal (OS) cells, editing their genomes to prevent the expression of vascular endothelial growth factor A (VEGFA), a key compound in the lifecycle of cancer cells.

Osteosarcoma is a common form of cancerous growth that affects bones, primarily in young people and children. The cancer has a 5-year survival rate of approximately 65% post treatment, one of the lowest for pediatric cancers. CRISPR/Cas9 gene editing systems have attracted significant recent interest with the promise of revolutionizing genetic engineering. However, when attempting to target specific cells in vivo, it has proven extremely difficult to achieve editing selectivity.

Zang’s team has taken CRISPR/Cas9 systems and linked them to long nucleotide aptamers. Aptamers can only bind to specific targets, and so the CRISPR/Cas9 is only free to act upon DNA close to the binding site.

The team chose to target DNA specific to the expression of VEGFA, which is found only in OS cancer cells, allowing these cells to be selectively edited to prevent expression. VEGFA plays a key role in the OS cancer lifecycle, involved in not only autocrine cell signaling but also angiogenesis (the namesake of cancerous tumors).

By preventing key signal expression, the group showed success in reducing bone lesions, lung metastasis and blood vessel growth; demonstrating that aptamer bound CRISPR/Cas9 could be utilized for the treatment of OS.

More importantly, their work provides a technique that could be used to target cancer selectively, without damaging healthy cell, as one of the researchers Lyu Aiping discussed: “The tumor-specific aptamers, when conjugated with PPC polymers encapsulating CRISPR/Cas9, may facilitate therapeutic genome editing in tumors.”

Sources: Zhang BT, Lu A, Zhang G, et al. Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma. Biomaterials. 147, 68 – 85 (2017);  Hong Kong Baptist University press release

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