<br>使用基于手性反向 L-DNA 的逻辑器件提高复杂环境中细胞鉴定的灵敏度,Advanced Science

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使用基于手性反向 L-DNA 的逻辑器件提高复杂环境中细胞鉴定的灵敏度
Advanced Science ( IF 14.3 ) Pub Date : 2024-10-14 , DOI: 10.1002/advs.202410642
Zixi Lai _{1,

2} , Di Jin ₂ , Yuan Tian ₂ , Xiaoxing Chen ₂ , Da Han _{2,

3} , Haige Chen ₂ , Junyan Wang ₃ , Yang Yang _{1,

4,

5}

Affiliation

准确鉴定和分离靶细胞对于精准诊断和治疗至关重要。在这种情况下，基于 DNA 适配体的 logic devices 具有明显的优势，因为它们可以高效地逻辑分析多个细胞表面标记物。然而，天然 DNA （D-DNA）对降解的敏感性会损害这些装置的敏感性和特异性，可能导致假阳性和假阴性结果，尤其是在复杂的生物环境中。为了解决这个问题，使用镜像 L-DNA（一种具有高生物稳定性的 D-DNA 手性分子）设计和开发了基于双适配体和三适配体的细胞表面逻辑器件。这些设备允许同时分析多个细胞表面蛋白，与基于 D-DNA 的 logic 设备相比，在细胞鉴定和分离方面具有更高的特异性。L-DNA 探针在基于双适配体和三适配体的逻辑装置用于靶细胞鉴定的 FBS 缓冲液中实现了 98.7% 和 70.5% 的灵敏度，而 D-DNA 探针仅显示出 27.9% 和 0.1%。相信 L-DNA 的高稳定性和标记细胞亚群的装置的高效率将在生命科学、生物医学工程和个性化医学中具有广泛的应用。

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Enhanced Sensitivity of Cell Identification in Complex Environments Using Chirally Inverted L-DNA-Based Logic Devices

Accurate identification and isolation of target cells are crucial for precision diagnosis and treatment. DNA aptamer-based logic devices provide a distinct advantage in this context, as they can logically analyze multiple cell surface markers with high efficiency. However, the susceptibility of natural DNA (D-DNA) to degradation can compromise the sensitivity and specificity of these devices, potentially leading to false-positive and false-negative results, particularly in complex biological environments. To address this issue, dual- and triple-aptamer-based cell-surface logic devices are designed and developed using mirror-image L-DNA, a chiral molecule of D-DNA with high biostability. These devices allow for simultaneous analysis of multiple cell surface proteins, achieving greater specificity in cell identification and isolation than D-DNA-based logic devices. The L-DNA probes realized 98.7% and 70.5% sensitivities in FBS buffer with dual- and triple-aptamer-based logic devices for target cell identification, while D-DNA probes only showed 27.9% and 0.1%. It is believed that the high stability of L-DNA and the high efficiency of the devices for labeling cell subpopulations will have broad applications in the life sciences, biomedical engineering, and personalized medicine.

更新日期：2024-10-14

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