公开(公告)号：WO2018031864A1

公开(公告)日：2018-02-15

申请号：PCT/US2017/046454

申请日：2017-08-11

Applicant: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM

Inventor： BROCK, Amy ,  AL'KHAFAJI, Aziz

IPC: C12N15/10 ,  C12N15/86 ,  C12N15/90 ,  C12N15/113 ,  C04B40/06

CPC classification number: C12N15/1065 ,  C12N9/22 ,  C12N15/10 ,  C12N15/102 ,  C12N15/11 ,  C12N15/111 ,  C12N15/63 ,  C12N2310/20 ,  C12N2740/16043 ,  C12Q2563/179

Abstract: Disclosed herein are methods and platforms related to modulating expression of a gene of interest within a select population of cells comprising: providing a population of cells; providing a vehicle, plasmid, vector or recombinant virus, or equivalent thereof, capable of stably expressing a guide nucleic acid comprising randomized barcodes, thereby producing a population of barcoded cells; allowing said barcoded cell to divide, thereby forming a barcoded progeny of cells; saving an aliquot of cells; identifying the barcode in a lineage of interest from the barcoded progeny of cells; reconstituting the aliquot of saved cells, and transforming the reconstituted aliquot of cells with a transcriptional element comprising a transcriptional effector, the barcode of the lineage of interest, and a gene of interest; utilizing the transcriptional effector to modify expression of the gene of interest within the lineage of interest.

Abstract translation: 本文公开了与在选择的细胞群体内调节感兴趣基因的表达有关的方法和平台，其包括：提供细胞群体; 提供能够稳定表达包含随机化条形码的指导核酸的载体，质粒，载体或重组病毒或其等同物，从而产生条形码细胞群; 允许所述条形码化细胞分裂，从而形成条形码化的细胞后代; 节省等分的细胞; 从条形码化细胞后代鉴定感兴趣谱系中的条形码; 重构保存的细胞的等分试样，并用包含转录效应物，感兴趣谱系的条形码和感兴趣的基因的转录元件转化重构的细胞等分试样; 利用转录效应子修饰感兴趣的谱系内感兴趣的基因的表达。