circGprc5a Promoted Bladder Oncogenesis and Metastasis through Gprc5a-Targeting Peptide

Bladder cancer is a serious cancer in the world, especially in advanced countries. Bladder cancer stem cells (CSCs) drive bladder tumorigenesis and metastasis. Circular RNAs (circRNAs) are involved in many biological processes, but their roles in bladder oncogenesis and bladder CSCs are unclear. Here, we identified that circGprc5a is upregulated in bladder tumors and CSCs. circGpr5a knockdown impairs the self-renewal and metastasis of bladder CSCs, and its overexpression exerts an opposite role. circGpr5a has peptide-coding potential and functions through a peptide-dependent manner. circGprc5a-peptide binds to Gprc5a, a surface protein highly expressed in bladder CSCs. Gprc5a knockout inhibits the bladder CSC self-renewal and metastasis. circGprc5a-peptide-Gprc5a can be utilized to target bladder cancer and bladder CSCs. Keywords: bladder cancer, cancer stem cells, Gprc5a, peptid

AAV13 Enables Precise Targeting of Local Neural Populations

As powerful tools for local gene delivery, adeno-associated viruses (AAVs) are widely used for neural circuit studies and therapeutical purposes. However, most of them have the characteristics of large diffusion range and retrograde labeling, which may result in off-target transduction during in vivo application. Here, in order to achieve precise gene delivery, we screened AAV serotypes that have not been commonly used as gene vectors and found that AAV13 can precisely transduce local neurons in the brain, with a smaller diffusion range than AAV2 and rigorous anterograde labeling. Then, AAV13-based single-viral and dual-viral strategies for sparse labeling of local neurons in the brains of C57BL/6 or Cre transgenic mice were developed. Additionally, through the neurobehavioral test in the ventral tegmental area, we demonstrated that AAV13 was validated for functional monitoring by means of carrying Cre recombinase to drive the expression of Cre-dependent calcium-sensitive indicator. In summary, our study provides AAV13-based toolkits for precise local gene delivery, which can be used for in situ small nuclei targeting, sparse labeling and functional monitoring