Characterization of In Vivo Selected Bacteriophage for the Development of Novel Tumor-Targeting Agents with Specific Pharmacokinetics and Imaging Applications.
Characterization of In Vivo Selected Bacteriophage for the Development of Novel Tumor-Targeting Agents with Specific Pharmacokinetics and Imaging Applications.
复制标题
用于开发具有特定药代动力学和成像应用的新型肿瘤靶向剂的体内选择噬菌体的表征。
DOI：
10.1007/978-1-4939-6911-1_29
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Deutscher,SusanL
中科院分区：
文献类型：
--
作者：
Newton-Northup,Jessica;Deutscher,SusanL
Bacteriophage (phage) display technology is a powerful strategy for the identification of peptide-based tumor targeting agents for drug discovery. Phage selections performed in vitro often result in many phage clones/peptides with similar properties and often similar sequence. However, these phage and corresponding peptides are selected, validated, and characterized outside the complicated milieu of a living animal. Thus, there is no guarantee that peptides from in vitro selections will successfully meet the requirements of an in vivo targeting compound. In comparison, in vivo phage display selections have the distinct advantage of identifying phage clones with robust pharmacokinetics and tumor/tissue targeting ability. This capacity has allowed for the identification of peptides with specific in vivo localization and/or clearance profiles. However, in vivo phage display selections also have the potential to result in an array of phage clones with various and unknown targets and little to no sequence similarity. Given these shortcomings, we have developed methods to select phage peptide display libraries in living mice to identify phage (and corresponding synthesized peptides) with specific clearance and/or tumor-targeting propensity. Additionally, we describe the use of labeled phage clones for the efficient screening of selected phage/peptides to aid in the identification and characterization of a phage clone with an optimal and specific pharmacokinetic profile.
