Key Laboratory of Biochip Technology, Biotech and Health Care , Shenzhen Research Institute of City University of Hong Kong , Shenzhen 518057 , China.
ACS Appl Mater Interfaces. 2019 Oct 23;11(42):38510-38518. doi: 10.1021/acsami.9b14324. Epub 2019 Oct 8.
We design and synthesize a sequence-defined α-l-threose nucleic acid (TNA) polymer, which is complementary to certain nucleotide sites of target anti-apoptotic proteins, BcL-2 involving in development and progression of tumors. Compared to scramble TNA, anti-BcL-2 TNA significantly suppresses target mRNA and protein expression in cancerous cells and shows antitumor activity in carcinoma xenografts, resulting in suppression of tumor cell growth and induction of tumor cell death. Together with good biocompatibility, very low toxicity, excellent specificity features, and strong binding affinity toward the complementary target RNAs, TNAs become new useful biomaterials and effective alternatives to traditional antisense oligonucleotides including locked nucleic acids, morpholino oligomers, and peptide nucleic acids in antisense therapy. Compared to conventional cancer therapy such as radiotherapy, surgery, and chemotherapy, we anticipate that this TNA-based polymeric system will work effectively in antisense cancer therapy and shortly start to play an important role in practical application.
我们设计并合成了一种序列定义的α-L-苏糖核酸（TNA）聚合物，它与参与肿瘤发生和发展的靶向抗凋亡蛋白 BcL-2 的某些核苷酸位点互补。与乱序 TNA 相比，抗-BcL-2 TNA 可显著抑制癌细胞中靶 mRNA 和蛋白的表达，并在癌异种移植中表现出抗肿瘤活性，从而抑制肿瘤细胞生长并诱导肿瘤细胞死亡。TNA 具有良好的生物相容性、极低的毒性、优异的特异性特征以及与互补靶 RNA 的强结合亲和力，成为新的有用的生物材料，并可有效替代传统的反义寡核苷酸，如锁核酸、吗啉代寡核苷酸和肽核酸，用于反义治疗。与传统的癌症治疗方法，如放疗、手术和化疗相比，我们预计这种基于 TNA 的聚合系统将在反义癌症治疗中有效发挥作用，并很快开始在实际应用中发挥重要作用。
