New Method of Transcytosis Pathway and Ligand Discovery

描述（由申请人提供）：XenoPort将利用NIH的资金开发一种新的噬菌体展示方法，用于鉴定治疗药物口服给药的有用的转细胞途径，并用于鉴定治疗分子。目前口服给药大分子和其他药物的方法不能提供足够的口服生物利用度。因此，必须确定新的肠道途径来运输更大量的化合物。不幸的是，目前的途径识别方法是不够的。XenoPort将通过开发一种在噬菌体颗粒上显示合成分子的新方法来解决这一问题，以充分利用噬菌体的灵敏和多功能性来显示分子文库。这些文库将用于筛选通过肠上皮引导最活跃的胞饮途径的受体配体，从而开发出适用于所有治疗领域的各种化合物的商业化技术平台。第一阶段的研究建立了构建、筛选和解码噬菌体上显示的合成化合物文库的基本方法。第二阶段将开发和评估一个模型肽库，其中包含非常多样化的合成化合物，以加强对内吞作用和胞吞作用中活性的新配体的发现。该技术将通过内部产品开发和战略合作伙伴关系实现商业化。

DESCRIPTION (provided by applicant): XenoPort will use NIH funding to develop a novel phage display method for identifying useful transcytotic pathways for oral administration of therapeutic drugs, and for identification of therapeutic molecules. Current methods for oral delivery of macromolecular and other drugs poorly absorbed by the intestine do not provide adequate oral bio-availability. Thus, new intestinal pathways to transport larger quantities of compound must be identified. Unfortunately, current methods of pathway identification are inadequate. XenoPort will address this problem by developing a new method for displaying synthetic molecules on phage particles to fully exploit the exquisite sensitivity and versatility of the phage for display of molecular libraries. These libraries will be used to screen for ligands to receptors directing the most active transcytosis pathways through the intestinal epithelium, enabling development of a commercial-ready technology platform adaptable to a wide variety of compounds in all therapeutic areas. Phase I studies established the fundamental method for constructing, screening and decoding libraries of synthetic compounds displayed on phage. Phase II will develop and evaluate a model peptide library of extraordinarily diverse synthetic compounds for enhanced discovery of novel ligands active in endocytosis and transcytosis. The technology will be commercialized via internal product development and strategic partnerships.