The Regulatory Framework in Biomedical Technologies

Human institutions--ways of organizing activities--affect the resilience of the environment. Locally evolved institutional arrangements governed by stable communities and buffered from outside forces have sustained resources successfully for centuries, although they often fail when rapid change occurs. Ideal conditions for governance are increasingly rare. Critical problems, such as transboundary pollution, tropical deforestation, and climate change, are at larger scales and involve nonlocal influences. Promising strategies for addressing these problems include dialogue among interested parties, officials, and scientists; complex, redundant, and layered institutions; a mix of institutional types; and designs that facilitate experimentation, learning, and change.

Zinc-finger nucleases (ZFNs) are targetable DNA cleavage reagents that have been adopted as gene-targeting tools. ZFN-induced double-strand breaks are subject to cellular DNA repair processes that lead to both targeted mutagenesis and targeted gene replacement at remarkably high frequencies. This article briefly reviews the history of ZFN development and summarizes applications that have been made to genome editing in many different organisms and situations. Considerable progress has been made in methods for deriving zinc-finger sets for new genomic targets, but approaches to design and selection are still being perfected. An issue that needs more attention is the extent to which available mechanisms of double-strand break repair limit the scope and utility of ZFN-initiated events. The bright prospects for future applications of ZFNs, including human gene therapy, are discussed.