The present invention pertains to a system of collaborative modifiers that are assembled into a multi molecule complex in vivo within a cell using bioorthogonal chemical reactions. The system of the invention is composed of multiple binding molecules having a binding affinity to a biological target macromolecule. Each of the binding molecules individually can easily be delivered into a target cell and then, when they bind to their target in the cell, will assemble into a higher multi-molecule complex on the target to increase overall binding specificity, selectivity and strength. Using the invention allows to mimic complex protein-protein interactions, for example the binding of biological macromolecules such as antibodies or receptor ligands with a set of small binding molecules that can be irreversibly assembled during use. The invention is of particular use for therapeutic applications involving intracellular drug targets and/or for crossing the blood brain barrier for targets within the central nervous system and/or for improving therapeutics penetration in tumour tissue. Thus, invention further provides pharmaceutical compositions comprising the components of the system of the invention, and their use in therapy of various diseases. Also provided are methods for the manufacture and design of the collaborative system and system components of the invention.La présente invention concerne un système de modificateurs collaboratifs qui sont assemblés en un complexe à molécules multiples in vivo dans une cellule à l'aide de réactions chimiques bio-orthogonales. Le système de l'invention est composé de multiples molécules de liaison ayant une affinité de liaison avec une macromolécule cible biologique. Les molécules de liaison peuvent chacune être facilement administrées individuellement dans une cellule cible puis, lorsqu'elles se lient à leur cible dans la cellule, s'assembler en un complexe à molécules multiples de poids moléculaire supérieur sur la cible pour augme
