Methods and compositions using genetic package display

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/70 (2006.01) C07H 21/04 (2006.01) C12N 15/00 (2006.01) C12N 15/10 (2006.01) C12P 21/06 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2453579

A genetic package display system and methodology for probing protein-protein interactions that lead to cell transduction, selecting and/or identifying internalizing ligands, target cells and tissues which internalize known or putative ligands, and cell transduction facilitating peptides is provided. A ligand displaying genetic package that carries a selectable marker (e.g., reporter, selection, etc.) and presents a ligand on its surface is utilized to identify internalizing ligands, tranduction facilitating peptides, and/or a variety of cells and tissue types for the ability to be successfully transduced by the ligand displaying genetic package. Also provided are methods for evolving a ligand displaying package to facilitate gene delivery or delivery of any desired agent (e.g., pharmaceutical, polypeptide, peptide, etc.) into a cell and/or targeting cellular compartments such as the nucleus, endosome, chloroplast, mitochondria, etc.

L'invention concerne un système et une méthodologie de présentation d'ensemble génétique permettant de sonder des interactions protéine-protéine conduisant à la transduction cellulaire, de sélectionner et/ou d'identifier des ligands d'internalisation, des cellules et des tissus cibles qui internalisent des ligands connus ou putatifs, et des peptides facilitant la transduction cellulaire. Un ensemble génétique de présentation de ligands portant un marqueur sélectionnable (par exemple, reporter, sélection, etc.) et présentant un ligand sur sa surface est utilisé pour identifier des ligands d'internalisation, des peptides facilitant la transduction et/ou une variété de types de cellule et de tissu en fonction de leur capacité à être transduit avec succès par l'ensemble génétique de présentation de ligand. L'invention concerne également des méthodes de développement d'un ensemble de présentation de ligands afin de faciliter l'apport de gène ou l'apport de n'importe quel agent voulu (par exemple pharmaceutique, polypeptide, peptide, etc.) dans une cellule et/ou permettant de cibler des compartiments cellulaires tels que le noyau, l'endosome, le chloroplaste, la mytochondrie, etc.

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