Self-Assembling Antisense Oligo-RNA Structures and M2-M1 Macrophage Phenotype Transformers for Cancer Treatment

The effectiveness of modern cancer therapy is significantly limited by rapid tumor adaptation, multiple drug resistance mechanisms, and the formation of an immunosuppressive microenvironment supported by M2 phenotype macrophages and latent viral infections. In this paper, we present an innovative binary therapeutic system designed to overcome these fundamental barriers.The first component of the system, MoLRx (mixture of antisense oligoRNA), is based on technology that converts the entire pool of eukaryotic RNAs from baker's yeast into antisense oligonucleotide structures via chemical modification of nucleotide bases (exo- and endo-cyclic). Due to the hyperactivated macropinocytosis characteristic of most solid tumors, MoLRx selectively penetrates cancer cells and forms stable hydrogen-ion bonds with the entire pool of cellular RNAs (mRNA, tRNA, rRNA). The absence of RNA repair mechanisms makes this multi-target approach resistant to tumor mutational adaptation and effectively blocks protein synthesis.The second component, Lipo-Liasten, is a liposomal penta-muryl peptide that acts on the tumor microenvironment, inducing macrophages to shift from the pro-tumor M2 phenotype to the pro-inflammatory and anti-tumor M1 phenotype. This leads to the reactivation of NK cells and the removal of the immunological block created by T-suppressors.The combined use of MoLRx and Lipo-liasten produces a synergistic effect: inhibiting tumor cell proliferation and restoring systemic antitumor immunity. The proposed strategy allows effective treatment of resistant and metastatic forms of cancer, while avoiding the development of tumor lysis syndrome and typical mechanisms of drug escape.