PRI-MIRNA LIBRARIES AND METHODS FOR MAKING AND USING PRI-MIRNA LIBRARIES

Provided are methods for the design, preparation, and use of non-native pri- microRNAs (pri-miRNAs), pri-microRNA (pri-miRNA) scaffolds, and libraries of non-native pri-miRNAs employing pri-miRNA scaffolds. Also provided are methods for identifying non- native pri-miRNAs, combinations of two or more non-native pri-miRNAs, and miRNAs derived from the processing of such non-native pri-miRNAs, which miRNAs exhibit one or more desired functional activities. Further provided are non-native pri-miRNAs, non-native pri-miRNA libraries, vectors comprising and for the expression of one or more non-native pre-miRNAs or for the expression of one or more miRNAs derived from the processing of one or more pre- miRNAs, and cells comprising one or more non-native pri-miRNAs or one or more miRNAs derived from the processing of such non-native pri-miRNAs, each of which pri-miRNAs, pri- miRNA libraries, vectors, and cells can be prepared by the methods disclosed herein. Still further provided are (a) methods for regulating, promoting, normalizing, restoring, inhibiting, or modulating a desired cellular phenotype including, for example, differentiation, de- differentiation, proliferation, growth, cell death, contact inhibition by expressing one or more pri- miRNAs or one or more miRNAs identified through the screening of a pri-miRNA library according to the methodology disclosed herein and (b) methods for the treatment of a disease or condition that associated with the expression of one or more gene or the production of one or more protein, wherein one or more aspect of the disease or condition is reduced in severity following the expression of one or more pri-miRNAs or miRNAs identified through the screening of a pri-miRNA library according to the methodology disclosed herein. L'invention concerne des procédés de conception, de préparation et d'utilisation de pri-microARN non natifs (pri-miARN), de supports pour pri-microARN (pri-miARN) et de banques de pri-miARN non natifs utilisant lesdits supports pour pri-miARN. L'invention concerne également des procédés d'identification de pri-miARN non natifs, de combinaisons d'au moins deux pri-miARN non natifs et de miARN issus de la transformation de tels pri-miARN non natifs, lesdits miARN présentant une ou plusieurs activités fonctionnelles recherchées. L'invention concerne, en outre, des pri-miARN non natifs, des banques de pri-miARN non natifs, des vecteurs comprenant au moins un pré-miARN non natif et servant à son expression o