Targeted delivery of RNA-based therapeutics for cancer therapy remains a challenge. We have developed a LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with tumor-targeting single-chain antibody fragment (scFv) for systemic delivery of small interfering RNA (siRNA) and microRNA (miRNA) into experimental lung metastasis of murine B16F10 melanoma. The siRNAs delivered by the scFv targeted nanoparticles efficiently downregulated the target genes (c-Myc/MDM2/VEGF) in the lung metastasis. Two daily intravenous injections of the combined siRNAs in the GC4-targeted nanoparticles significantly reduced the tumor load in the lung. miRNA-34a (miR-34a) induced apoptosis, inhibited survivin expression, and downregulated MAPK pathway in B16F10 cells. miR-34a delivered by the GC4-targeted nanoparticles significantly downregulated the survivin expression in the metastatic tumor and reduced tumor load in the lung. When miR-34a and siRNAs were co-formulated in GC4-targeted nanoparticles, an enhanced anticancer effect was observed.

Lung cancer is the leading cause of cancer‐related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple‐neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. Cancer 2015;121:3080‐8. © 2015 American Cancer Society.

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Sequence variation in tRNA genes influences the structure, modification, and stability of tRNA; affects translation fidelity; impacts the activity of numerous isodecoders in metazoans; and leads to human diseases. To comprehensively define the effects of sequence variation on tRNA function, we developed a high-throughput in vivo screen to quantify the activity of a model tRNA, the nonsense suppressor SUP4 oc of Saccharomyces cerevisiae. Using a highly sensitive fluorescent reporter gene with an ochre mutation, fluorescence-activated cell sorting of a library of SUP4 oc mutant yeast strains, and deep sequencing, we scored 25,491 variants. Unexpectedly, SUP4 oc tolerates numerous sequence variations, accommodates slippage in tertiary and secondary interactions, and exhibits genetic interactions that suggest an alternative functional tRNA conformation. Furthermore, we used this methodology to define tRNA variants subject to rapid tRNA decay (RTD). Even though RTD normally degrades tRNAs with exposed 59 ends, mutations that sensitize SUP4 oc to RTD were found to be located throughout the sequence, including the anti-codon stem. Thus, the integrity of the entire tRNA molecule is under surveillance by cellular quality control machinery. This approach to assess activity at high throughput is widely applicable to many problems in tRNA biology.