Synthetic α- L-Threose Nucleic Acids Targeting BcL-2 Show Gene Silencing and In Vivo Antitumor Activity for Cancer Therapy.

We design and synthesize a sequence-defined TNA polymer which is complementary to the certain nucleotide site of target anti-apoptotic proteins BcL-2 involving in the development and progression of tumors. Comparing to the 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 its good biocompatibility, very low toxicity, excellent specificity features and strong binding affinity towards the complementary target RNAs, TNAs become new useful biomaterials and effective alternatives to traditional antisense oligonucleotides including LNAs, MOs, and PNAs in antisense therapy. Comparing to the 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.