2017年6月8日，国际著名学术杂志《Cell》子刊《Cell Chemical Biology》杂志在线发表了美国Scripps研究所Peter G. Schultz研究团队和北京大学药学院刘涛研究团队合作的一篇研究论文，研究联合建立了包含近千种药用蛋白的分泌蛋白库，并基于该库创建了反转录病毒介导的单细胞筛选方法，对发现具有全新药用价值的蛋白和新的抗体药物的治疗靶点具有重大意义。刘涛研究员为第一作者兼主要责任通讯作者，Peter G. Schultz教授为共同通讯作者。
人类基因组中有超过2000个基因编码分泌蛋白，约占整个基因组的10%，其中富含调控生命活动的具有重大药用价值的蛋白，包括激素、细胞因子、生长因子、趋化因子和蛋白酶等。然而目前大多数分泌蛋白的功能尚不清楚，同时缺乏有效的专门针对分泌蛋白的筛选方法，严重制约了新的药用蛋白和药物靶点蛋白的发现。
刘涛研究团队利用反转录病毒，通过一个细胞一个基因(OGOC, one gene one cell)的感染技术，利用分泌蛋白在细胞膜外定位的特点，实现了分泌蛋白基因库的富集。基因深度测序(NGS)结果表明，共有3699个基因被富集出来，其中已知的分泌型蛋白基因的读长频率占了77.77%。该团队还建立了单细胞水平的自分泌筛选系统，这种基于反转录病毒的高通量新型筛选系统避免了蛋白的表达纯化，和基于96孔板的传统筛选方式相比，省时省力，为筛选在生命调控过程中具有重大生物学意义以及药用价值的蛋白奠定了基础。
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Over 2,000 human proteins are predicted to be secreted, but the biological function of the many of these proteins is still unknown. Moreover, a number of these proteins may act as new therapeutic agents or be targets for the development of therapeutic antibodies. To further explore the extracellular proteome, we have developed a secretome-enriched open reading frame (ORF) library that can be readily screened for autocrine activity in cell-based phenotypic or reporter assays. Next-generation sequencing (NGS) and database analysis predict that the library contains approximately 900 ORFs encoding known secreted proteins (accounting for 77.8% of the library), as well as genes encoding potentially unknown secreted proteins. In a proof-of-principle study, human TF-1 cells were screened for proliferative factors, and the known cytokine GMCSF was identified as a dominant hit. This library offers a relatively low-cost and straightforward approach for functional autocrine screens of secreted proteins.
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