ZFP Transcription Factors (ZFP TFs)
Sangamo's ZFP TFs are novel transcription factors that mimic the natural mode of gene regulation. We engineer ZFPs to recognize a DNA sequence close to or within a gene of choice. By attaching a functional domain such as a naturally occurring “gene activation” or a “gene repression” domain to that ZFP we generate a ZFP TF that can up-regulate (activate) or down-regulate (repress) the expression of the target gene.
Regulating an endogenous gene (i.e. a gene in an organism’s genome) with a ZFP TF mimics the way a cell normally regulates the gene which has important implications for the biological outcome that we are trying to achieve.
For instance, we are developing a ZFP TF which selectively down-regulates the mutant allele of the Huntingtin (HTT) gene, the gene responsible for causing Huntington's disease. By using a ZFP TF to turn this gene off, we can selectively decrease production of the patient’s mutant Huntingtin protein while leaving expression of the normal Huntingtin protein untouched. This approach has shown promising results in several animal models of disease. We are currently testing this ZFP TF in preclinical studies.
What are the advantages of ZFP TFs?
We believe that our ZFP TF technology has several technical advantages compared with other technologies. Among the advantages of this ZFP TF-based gene regulation approach are:
- ZFPs normally and naturally regulate genes in all higher organisms
- ZFPs can be designed to recognize unique DNA sequences within a large complex genome
- ZFP TFs can both activate or repress genes, enhancing their versatility
- ZFP TFs can be used to regulate the genes of humans, animals, plants, microbes and viruses
- ZFP TFs have proven effectiveness from cell models through to the corresponding animal models
- ZFP TFs have been tested in humans and to date have an excellent safety profile
- ZFP TFs can themselves be regulated, allowing conditional and reversible regulation of a gene
- ZFP TFs can be used to regulate an endogenous cellular gene rather than a transgene and thus provide a workaround solution for genes whose cDNAs are patented