Synthetic α-l-Threose Nucleic Acids Targeting BcL-2 Show Gene Silencing and in Vivo Antitumor Activity for Cancer Therapy,ACS Applied Materials & Interfaces

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Synthetic α-l-Threose Nucleic Acids Targeting BcL-2 Show Gene Silencing and in Vivo Antitumor Activity for Cancer Therapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-10-08 , DOI: 10.1021/acsami.9b14324
Fei Wang , Ling Sum Liu , Cia Hin Lau , Tristan Juin Han Chang , Dick Yan Tam , Hoi Man Leung , Chung Tin , Pik Kwan Lo ₁

Affiliation

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.

中文翻译：

靶向BcL-2的合成α-1-苏糖核酸显示基因沉默和体内抗肿瘤活性的癌症治疗。

我们设计并合成序列定义的α- l-苏糖核酸（TNA）聚合物，与靶抗凋亡蛋白BcL-2的某些核苷酸位点互补，参与肿瘤的发生和发展。与争夺TNA相比，抗BcL-2 TNA显着抑制癌细胞中的靶mRNA和蛋白表达，并在异种癌移植物中显示出抗肿瘤活性，从而抑制了肿瘤细胞的生长并诱导了肿瘤细胞的死亡。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对互补靶RNA的强结合亲和力，成为反义疗法中新的有用的生物材料，是传统反义寡核苷酸（包括锁定核酸，吗啉代寡聚物和肽核酸）的有效替代品。与传统的癌症疗法（例如放疗）相比，

更新日期：2019-10-10

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