Relating chemical and biological diversity space: a tunable system for efficient gene transfection

Polyethyleneimine (PEI), a well-established nonviral transfection reagent, was combinatorially modified with varying proportions of methyl, benzyl, and n-dodecyl groups to create a library of 435 derivatized polymers. Screening of this library for transfection, DNA binding, and toxicity allows systematic correlation of the biological properties of our polymers to their derivatizations. Combinations of derivatizations bring about a 100-fold variation in transfection efficiency between library members. The best PEI derivatives exhibit increases in transfection efficiency of more than 80-fold over unmodified PEI (up to 28+/-7 % of cells transfected) and rival commercial reagents such as Lipofectamine 2000 (21+/-10 %) and JetPEI (32+/-5.0 %). In addition, we can identify compounds that are specifically tuned for efficient transfection in CHO-K1 over Ishikawa cells and vice versa, demonstrating that the approach can lead to cell-type selectivity of at least one order of magnitude. This work demonstrates that multivalent derivatization of a polymeric framework can create functional diversity substantially greater than the structural diversity of the derivatization building blocks and suggests an approach to a better understanding of the molecular underpinnings of transfection as well as their exploitation.     

Of managers,ideas and jesters,and the role of information technology

In this article we examine the role of information technology in the relationship between ideas and managers. In particular, we explore the capacity of ideas to take hold of managers and organizations, facilitated by information technology, and contest the dominant view that ideas are passive instruments for choice. Rather, we claim that ideas tend to own us. We invert the position of the human actor and the idea, and give ideas the character of an enactor, a prerequisite for an entity that may “imprison humans”. Strategies for detachment are then needed such as the old institution of jestering.