HKU Develops a New Platform for Accelerating Protein Engineering and Optimising CRISPR Protein for Higher Fidelity in Gene Editing
CRISPR, the revolutionary technology that allows scientists to edit genes by finding and cutting a specific strand of DNA, is often likened to a pair of scissors. However, issues can arise with the technique if the cut is not accurate.
This is what led a HKUMed team from the School of Biomedical Sciences to develop CombiSEAL, a screening platform to ensure the utmost accuracy for the protein “scissors” used for gene editing.
Their work began by characterising 948 combination mutants of Streptococcus pyogenes Cas9, which is widely used for gene editing. Through screening, they identified Opti-Cas9, which was found to have enhanced editing specificity without sacrificing potency as well as having a broad targeting range.
Their platform is able to test tens of thousands of potential proteins simultaneously, bringing down costs. The screening is designed to achieve more accurate therapeutic editing to avoid inadvertently introducing any other problems into the DNA sequence that could cause problems such as cancer.
Alongside optimising the platform for applications beyond CRISPR, the team is now working to harness artificial intelligence to test ten times as many proteins at once.
嶄新基因篩選平台 確保基因編輯準確
CRISPR 基因編輯酶為編緝基因的革命性科技，常被譬為科學家尋找及剪除特定氨基酸的「剪刀」。然而「剪除」失誤，後果不堪設想。有見及此，港大生物醫學學院的團隊建立了CombiSEAL基因篩選平台，以確保「剪刀」下刀準確無誤。
團隊首先快速建造948個最受廣泛應用的SpCas9變體。通過篩選，團隊成功篩選出新變體Opti-SpCas9，在不損失活性及靶點選擇範圍的同時，降低基因編輯錯誤的可能性。
CombiSEAL能夠同時測試數以萬計的蛋白質，以減低成本。篩選過程經過精心設計，以達至更精準的編輯治療，避免無意間將問題帶進基因序列，產生癌症等問題。
團隊現時積極提升平台表現，以將其應用於CRISPR以外的領域。團隊現在亦嘗試加入人工智能，進一步把測試規模擴大至超過現時數目十倍以上的蛋白質。