Team:Harvard/Human Practices/Timeline

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Zinc Finger Historical Timeline

  • Discovery of the zinc finger protein

    Jonathon Miller, A. D. McLachlan, and Sir Aaron Klug first identify the repeated binding motif in Transcription Factor IIIA and are the first to use the term ‘zinc finger.'

  • First crystal structure of a 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.

  • CEO Edward Lanphier founds Sangamo Biosciences

    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.

  • Srinivasan Chandrasegaran publishes work on fusing the Fok I nuclease to 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 enters the public sector

    In April 2000, five years after its founding, Sangamo Biosciences goes public offering 3.5 million shares at a starting value of $15 per share.

  • Sangamo patents zinc finger nuclease technology

    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.

  • Rapid open source production of zinc finger nucleases becomes available

    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.

  • First zinc finger nuclease in clinical trials

    Sangamo and University of Pennsylvania begin the first human clinical trials with a zinc finger nuclease designed to target the CCR5 gene and inhibit HIV.

  • Context-dependency improves open-source zinc finger engineering

    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.

  • Harvard iGEM develops a novel method to engineer custom 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. Our work greatly increases the ease of access to zinc finger technology for researchers worldwide.