|Z-DNA||new form of DNA dubbed Z-DNA that coils in the shape of a left-handed screw.|
|ZINC FINGER PROTEIN||independently folding domains of about 30 amino acid residues centered on a zinc ion|
|ZINC FINGER PROTEIN TF||are novel transcription factors designed and engineered by Co. scientists to regulate the expression of target endogenous genes.
Figure 1: ZFP transcription factors have two domains: A recognition domain that recognizes and binds to a specific DNA sequence, and a functional domain that provides a specific activity for the protein.
Our technology is based upon the engineering of a naturally occurring class of DNA transcription factors called zinc finger DNA-binding proteins, or ZFPs. The DNA recognition and binding function of ZFPs can be used to target a variety of functional domains to a gene-specific location. The two-component structure of our engineered ZFP TFs is modeled on the structure of naturally occurring transcription factors.
Consistent with the two-domain structure of ZFP TFs, we take a modular approach to their design. The recognition domain is composed of two or more zinc fingers; each finger recognizes and binds to a three base pair sequence of DNA and multiple fingers can be linked together to more precisely recognize longer stretches of DNA. By modifying those portions or the critical amino acid contacts of a ZFP that interact with DNA, we can engineer novel ZFPs capable of recognizing defined DNA sequences in any gene.
We can combine engineered ZFPs with a variety of different functional domains to generate proteins that can activate or repress gene expression. In addition, we can engineer a ZFP TF with a functional domain that has a “switch” component, enabling us to regulate its activity and thus the expression of its target gene using a small molecule drug (Regulatable Gene Therapy 76k PDF). The capability for regulated expression is important particularly for the use of ZFP TFs in gene therapy applications (as ZFP Therapeutics) as it allows control of both the duration of the exposure to the therapeutic agent and gives the flexibility of more precise dosing. Another application of our technology combines the gene targeting function of an engineered ZFP and the functional domain of a restriction endonuclease, an enzyme that cuts DNA. The resulting protein, a ZFP-restriction enzyme may be used to facilitate the replacement of a specific DNA sequence within a gene carrying a disease-causing mutation with a corrected sequence, thus restoring gene function.
|ZOLLINGER-ELLISON SYNDROME||Clinical Syndrome characterized by Excessive Secretion of Gastric Juice, Hyperplasia of Gastric Mucosa, & Severe Peptic Ulcer Disease; due to the presence of Gastrin-producing Tumors (Gastrinomas)|