Sir Aaron Klug first identifies the repeated binding motif in Transcription Factor IIIA and is the first to use the term ‘zinc finger’.

Carl Pabo and Nikola Pavletich of Johns Hopkins University solve the crystal structure of zif268, now the most-commonly studied zinc finger. This paved the way for construction of binding models to describe how zinc fingers bind to DNA, setting the foundation for future custom engineering of zinc finger proteins.

Edward Lanphier leaves Somatix Therapy Corporation and makes a deal for exclusive rights to the work of Srinivan Chandrasegaran of Johns Hopkins University who combined the Fok I nuclease with zinc fingers.

By attaching nuclease proteins to zinc fingers, a new genome editing tool was created. The DNA-binding specificity of zinc fingers combined with the DNA-cutting ability of nucleases opened up possibilities for future research in gene therapy by allowing researchers to directly modify the genome though use of zinc finger nucleases.

Sangamo's patent, titled "Nucleic acid binding proteins (zinc finger proteins design rules)", ensures that any use or production of zinc fingers with attached nucleases is the intellectual property of Sangamo.

Researcher Keith Joung of Harvard University and Mass. General Hospital develops a method for making zinc finger nuclease proteins that bind to custom target sequences, utilizing a bacterial two-hybrid screening system to identify specific zinc finger binders to a DNA sequence of interest.

Sangamo licenses its proprietary zinc finger engineering algorithms and procedures to Sigma-Aldrich to allow for larger-scale production and sale of zinc finger nuclease proteins. The license allows Sigma-Aldrich to sell custom zinc finger nuclease protein pairs for approximately $30,000 each.

Keith Joung publishes tables of zinc finger binding sites that account for context-dependent effects and can be rearranged to form custom zinc finger proteins that bind to a variety of DNA sequences. This greatly increases the ease of engineering novel zinc fingers based on the structures of previously characterized zinc fingers.

Using novel integration of existing technologies, we have developed a rapid, comparatively low-cost, open source method for making thousands of custom zinc fingers by integrating MAGE, lambda red, and chip-based synthesis technologies. This will grant researchers much greater access to zinc finger technology, allowing them to bypass patent restrictions imposed on technology sold by Sangamo Biosciences.