Targeting the Anterior Segment with Homing Peptides from Phage Display

使用噬菌体展示的归巢肽靶向眼前节

• 批准号: 8651496
• 负责人: Donna M Peters
• 金额: $ 18.44万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2015-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8651496
• 关键词: Accounting; Affect; Affinity; African American; Anterior; Anterior eyeball segment structure; Aqueous Humor; Bacteriophage T7; Bacteriophages; Biological Markers; Blindness; Blood Circulation; Cells; Disease; Drainage procedure; Drug Delivery Systems; Drug Targeting; Family suidae; Gene Delivery; Generations; Glaucoma; Goals; Grant; Heterogeneity; Homing; Image; Imaging Device; Integrins; Laboratories; Lead; Libraries; Modification; Molecular; Monitor; Operative Surgical Procedures; Organ Culture Techniques; Peptides; Phage Display; Pharmaceutical Preparations; Physiologic Intraocular Pressure; Publishing; Retinal Ganglion Cells; Rho-associated kinase; Stem cells; Stents; Structure of sinus venosus of sclera; System; Therapeutic; Tissues; Toxic effect; Trabecular meshwork structure; Viral; Viral Vector; Virus; aqueous; cell type; drug efficacy; gene therapy; glaucoma surgery; in vivo; inhibitor/antagonist; interest; kinase inhibitor; public health relevance; screening; stem cell differentiation; targeted delivery; tool; vector

DESCRIPTION (provided by applicant): This is a new application for a R21. The long-term objective of this grant is to use phage display libraries to identify tissue specific homing peptids for the trabecular meshwork (TM) that can be used as therapeutic delivery agents to control and lower intraocular pressure. The glaucomas, which lead to irreversible loss of retinal ganglion cells, affect approximately 67 million people worldwide. They are commonly associated with elevated levels of intraocular pressure (IOP) due to a reduction in aqueous humor outflow from the TM. Although reduced drainage of aqueous humor through the TM accounts for at least 90% of abnormalities resulting in glaucoma, there are very few drugs that can specifically target the TM with the goal of increasing aqueous humor outflow. One way to target drug deliver is to use homing peptides attached to the compound or cloned into the viral coat. These homing peptides are then used to generate tissue specific delivery systems in vivo and reduce targeting of unwanted tissue interactions. To identify homing peptides for the TM, we plan to use the Cx7C phage library previously shown to produce in vivo tissue specific homing peptides. We also plan to generate a phage display library that is biased towards the a4b1 integrin sequence motif, PRARI. Published studies from our laboratory have shown that this PRARI peptide can be used to target the TM. In past studies, this peptide caused an increase in outflow facility in cultured anterior segments. It is our goal to produce a more specific PRARI peptide with a higher affinity. The identification of homing peptides for the TM would have multiple uses for the treatment for glaucoma. In addition to targeted drug delivery and generation of tissue specific viral vectors, these peptides could be used as biomarkers for cell stem delivery and as imaging tools for glaucoma surgery.

描述（由申请人提供）：这是R21的新应用程序。该赠款的长期目标是使用噬菌体显示文库来识别小梁网植物（TM）的组织特异性归巢肽，可用作可以用作治疗递送剂来控制和降低眼内压力。绿哥膜导致视网膜神经节细胞的不可逆转损失，全世界大约有6700万人。它们通常与眼内压（IOP）升高有关，因为从TM中流出了水性幽默。尽管通过TM的水性幽默的排水减少了，至少有90％的异常，导致青光眼，但很少有药物可以专门针对TM，其目的是增加水性幽默流出。靶向药物的一种方法是使用附着在化合物上或克隆到病毒外套中的归巢肽。然后，这些归巢肽用于在体内生成特定于组织的递送系统，并减少对不良组织相互作用的靶向。为了鉴定TM的归巢肽，我们计划使用先前显示的CX7C噬菌体文库来产生体内组织特定的归巢肽。我们还计划生成一个偏差偏向A4B1整合素序列图案Prari的噬菌体显示库。我们实验室发表的研究表明，该prari肽可用于靶向TM。在过去的研究中，这种肽导致培养的前部段的流出设施增加。我们的目标是生产具有更高亲和力的更具体的prari肽。 TM的归因肽的鉴定将有多种用于青光眼治疗的用途。除了有针对性的药物递送和组织特定病毒载体的产生外，这些肽还可以用作细胞茎递送的生物标志物，并用作青光眼手术的成像工具。