Carrier assembly carrying gene element combination, recipient cell library, preparation and screening methods and application

Abstract

The invention provides a carrier assembly carrying a gene element combination, a recipient cell library, a preparation and screening method and an application, the recipient cell library is formed byfusing cells and the carrier assembly, and the carrier assembly at least carries three gene elements, respectively a plurality of first gene elements encoding one or more idiotypic synNotch receptors,respectively; a second gene element carrying one or more gene loops; a third gene element encoding one or more idiotypic chimeric antigen receptors. Wherein, when the first genetic element encodes one idiotypic synNotch receptor, the third genetic element must encode at least three idiotypic chimeric antigen receptors, and when the third genetic element encodes one idiotypic chimeric antigen receptor, the first genetic element must encode three idiotypic synNotch receptors. The gene loop is pre-programmed, a regulatory homeopathic factor is combined with a transcription factor, upon activation of the synNotch receptor encoded by the first gene element, the chimeric antigen receptor encoded by the third gene element is controllably expressed.

Description

technical field [0001] The present invention relates to the fields of biomedical engineering technology and synthetic biology, in particular to a gene element combination and a synNotch receptor carrying the combination and an artificial receptor cell library, and the method for preparing and constructing the gene element combination and the cell library, aiming at Screening methods for in vivo antigens and / or in vitro antigens, and the use of cell libraries are described in detail. Background technique [0002] For major human diseases represented by malignant tumors, they are characterized by high variability, individual differences, heterogeneity, and evolution. The identification of specific tumor antigens is difficult, diverse, and highly individualized, and malignant tumor tissues can undergo biological evolution with the development of the disease and the pressure of treatment methods, with a large degree of variability. [0003] Library technologies such as phage di...

AI Technical Summary

Problems solved by technology

Although this patent document describes the further screening method of CAR library using general technology, such as using iQue TM Screener (Intellicyt, Albuquerque, NM) (a high-throughput flow cytometer) for high-throughput testing of individual CAR molecules, but this document only discloses the preparation of multiple CARs, and the screening direction of CAR cell libraries cannot Changes in response to antigenic changes, no improvement in screening potential for lack of efficiency

On the other hand, although both are artificial receptors, the activation accuracy of the CAR receptor itself is much lower than that of the synNotch receptor, which is not conducive to the design of gene circuits

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