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常凌乾老师课题组

Research Focus

 

  Recent gene and antibody therapies, such as gene editing (CRISPR, Nobel Prize 2020) and immunotherapy (PD-L1, Nobel Prize 2018), have brought new hope to the treatment of major diseases, increasing the clinical demand for the delivery of macromolecular drugs like genes and antibodies. However, when conventional drug delivery methods (systemic circulation) are used for these macromolecules, several significant challenges arise: (1) Low efficiency: Due to organ and cellular barriers, the delivery efficiency and stability to target organs/cells are low; (2) Safety risks: Systemic delivery can lead to the accumulation of macromolecules in non-target organs, causing toxicity, carcinogenesis, and other issues in these areas.

    To address these challenges, our research group has proposed the development of a high-efficiency organ-specific delivery biochip: (1) We designed a flexible, fully implantable Nano-Electroporation (NEP) organ chip, which uses electrophoresis through nanoscale channels to improve drug delivery efficiency. By reducing safety risks through cell voltage partitioning, the in vivo delivery efficiency was increased from less than 1% to over 30%. This technology successfully reprogrammed dermal cells into vascular endothelial cells, promoting collateral vessel regeneration and blood flow, thereby delaying tissue necrosis (Nature Nanotechnology, 2017, 12, 974); (2) It also demonstrated efficacy in intestinal injury repair (Nature Electronics, 2024); and (3) Achieved efficient in situ gene delivery in internal organs (such as the breast and liver), where, for the first time, the evolution of breast cancer from a single-cell mutation to tumor formation was observed (under revision).

Cell therapy

  A rapid and precise assessment of targeted cancer cell therapy was achieved by using Nano-Electroporation (NEP) technology to quickly deliver novel fluorescent probes into tumor cells, enhancing the speed and efficiency of intracellular gene detection. The use of biochips to construct single-cell arrays improved the spatiotemporal specificity of detection, enabling real-time, quantitative analysis (Nature Photonics, 2024). At Peking University Cancer Hospital, a follow-up study of 71 lung cancer patients demonstrated that this strategy achieved over 90% concordance with patient treatment outcomes, significantly outperforming tissue biopsy (50%) (PNAS, 2024), while reducing the detection time from the conventional one day to 30 minutes.

 Simultaneously, a multi-dimensional analysis was conducted to explore the relationship between exosomal contents and gene regulation in cancer cells (J. Am. Chem. Soc., 2022, 144, 9443); the correlation between gene mutations and drug resistance (Nano Letters, 2021, 21, 4878, cover article); the relationship between mRNA regulation, cell migration, and drug resistance within cancer cells (Nano Letters, 2016, 16, 5326); gene regulation and mechanical properties, as well as cell motility (Small, 2022, 18, 2016196); and the differential protein expression and cell motility in cancer cells (Biosensors & Bioelectronics, 2022, 210, 114281).


Cell detection

   

   A rapid and precise evaluation of targeted cancer cell therapy has been achieved by utilizing Nano-Electroporation (NEP) technology to quickly deliver novel fluorescent probes into tumor cells, significantly enhancing the speed and efficiency of intracellular gene detection. By constructing single-cell arrays on biochips, this method improved the spatiotemporal specificity of detection, enabling real-time, quantitative analysis (Nature Photonics, 2024). A follow-up study of 71 lung cancer patients at Peking University Cancer Hospital demonstrated that this strategy achieved over 90% concordance with predictions of patient treatment outcomes, far surpassing tissue biopsy accuracy (50%) (PNAS, 2024), while reducing the detection time from the conventional one day to just 30 minutes.

  In addition, multi-dimensional analyses were conducted to explore various aspects of cancer cell biology, including the relationship between exosomal contents and gene regulation (J. Am. Chem. Soc., 2022, 144, 9443); the connection between gene mutations and drug resistance (Nano Letters, 2021, 21, 4878, cover article); the regulation of mRNA within cancer cells and its impact on cell migration and drug resistance (Nano Letters, 2016, 16, 5326); the relationship between gene regulation, mechanical properties, and cell motility (Small, 2022, 18, 2016196); and the link between differential protein expression and cell motility (Biosensors & Bioelectronics, 2022, 210, 114281).

Cell sampling