EFFICIENT METHODS FOR ASSESSING AND VALIDATING CANDIDATE PROTEIN-BASED THERAPEUTIC MOLECULES ENCODED BY NUCLEIC ACID SEQUENCES OF INTEREST

A method of determining at least one quantitative or qualitative pharmacological, physiological and/or therapeutic, parameter or effect of a recombinant gene product in vivo, the method comprises (a) obtaining at least one micro-organ explant from a donor subject, the micro-organ explant comprising a population of cells, the micro-organ explant maintaining a microarchitecture of an organ from which it is derived and at the same time having dimensions selected so as to allow diffusion of adequate nutrients and gases to cells in the micro-organ explant and diffusion of cellular waste out of the micro-organ explant so as to minimize cellular toxicity and concomitant death due to insufficient nutrition and accumulation of the waste in the micro-organ explant, at least some cells of the population of cells of the micro-organ explant expressing and secreting at least one recombinant gene product; (b) implanting the at least one micro-organ explant in a recipient subject; and (c) determining the at least one quantitative or qualitative pharmacological, physiological and/or therapeutic, parameter or effect of the recombinant gene product in the recipient subject.