The Most Precise Genome Editing Technology

Treating genetic disorders begins with a double strand break of exquisite precision

At the cutting edge

For years we have been able to read our genome – now genome editing allows us to design therapeutics that can rewrite or modify the genome in a living cell, providing a new solution for genetic disease. As the leader in therapeutic genome editing, Sangamo has not only blazed the trail in this new and exciting field of medicine but has built the most advanced, flexible and precise technology.

Our ZFN genome editing technology is based on Zinc Finger Proteins

Our proprietary technology is based on a naturally occurring class of proteins called zinc finger DNA-binding proteins (ZFPs) which recognize and bind to specific sequences of DNA. We can engineer them to bind to virtually any sequence that we choose.  We can attach a nuclease, a functional domain that cuts DNA, to this ZFP portion, to make a zinc finger nuclease (ZFN).

How does it work?

It all starts with a targeted double strand break in the DNA…

When a pair of ZFNs binds to their DNA target sites, in the correct orientation and spacing, the DNA sequence is cut between them. This break in the DNA triggers a natural process of DNA repair in the cell. The repair process can be harnessed to achieve one of several outcomes that may be therapeutically useful.

We can achieve several therapeutic outcomes with ZFN-mediated editing

Using ZFNs we can knock out a gene or insert a therapeutic gene into the genome in a targeted fashion. If cells are only treated with ZFNs, the repair process frequently results in the rejoining of the two broken ends of the DNA, which disrupts the original DNA sequence and therefore also gene function.  In contrast, a therapeutic gene can be inserted if cells are treated with ZFNs in the presence of an additional “donor” DNA sequence.

The advantages of ZFN-mediated genome editing

We believe that our ZFN technology has advantages over other genome editing technologies and traditional gene therapy approaches.

The ability to place a gene-sized segment of DNA into a pre-determined location in the genome, with singular specificity, eliminates insertional mutagenesis concerns associated with traditional lentiviral gene replacement approaches and broadens the range of mutations of a gene that can be corrected in a single step.

ZFNs provide the best platform for therapeutic genome editing because they enable:

  • Precision: Exquisite targeting precision -- high design density means we can place ZFNs at virtually any sequence in the genome
  • Specificity: We can quickly engineer ZFNs to be highly specific -- engineered to engage a target site with no meaningful off-target effects
  • Efficiency: We can quickly engineer ZFNs to be extremely efficient -- to cut DNA with high on-target efficiency (>90% for initial lead design screens), while retaining excellent specificity