Clinical Trials

Date: 2019-03-08

Type of information: Publication of results in a medical journal

phase: preclinical

Announcement: publication of results in Nature Communications

Company: Sangamo Therapeutics (USA - CA)

Product: zinc finger nuclease (ZFN) platform technology

Action mechanism:

  • gene editing/gene therapy. ZFN technology is an engineerable gene editing platform that is currently being evaluated in clinical trials for mucopolysaccharidosis type I (MPS I), MPS II, hemophilia B, beta thalassemia and sickle cell disease.


Therapeutic area:


Trial details:

Latest news:

  • • On March 8, 2019, Sangamo Therapeutics announced the publication in Nature Communications of improvements to its zinc finger nuclease (ZFN) platform technology, which yield a 64-fold increase in the diversity of ZFNs available for targeting any DNA segment. As demonstrated in the manuscript, this improved targeting capability enables highly precise editing of chosen genomic loci. The manuscript, "Diversifying the Structure of Zinc Finger Nucleases for High-Precision Genome Editing", describes protein engineering work by Dr. David Paschon and colleagues at Sangamo that has led to the development of new ZFN architectures. The modifications include the reversal of the order of the DNA binding and nuclease domains, as well as the incorporation of new linkers that enable base skipping between otherwise adjacent fingers within each ZFN.
  • "In developing nucleases for any therapeutic application, a critical requirement is the ability to position the double-stranded break for maximal clinical efficacy," said Ed Rebar, Ph.D., Sangamo's Chief Technology Officer. "In many cases, this consideration restricts the optimal cleavage target to a narrow sequence window, and for this reason, increasing targeting precision has been a longstanding concern in the field. The new architectures, which have substantially improved our targeting capabilities, will help ensure that we can target the optimal window for any therapeutic application. This speaks to the versatility of our ZFN genome editing technology."
  • Sangamo researchers developed new linkers that attach the FokI nuclease domain to the amino terminus of the DNA-binding zinc finger array, as opposed to the carboxy terminal attachment used in canonical ZFNs. This modification allows the design of nucleases in which each ZFN of a dimer is able to recognize either DNA strand, yielding three alternative ZFN dimer configurations, effectively increasing the number of design options for any target sequence by a factor of four. New linkers were also developed that allow base-skipping between adjacent fingers within a zinc finger array. These new linkers enable an engineered ZFN to bind alternative, partially frame-shifted DNA sequences with new zinc finger designs while maintaining the same cleavage site, thereby increasing the number of design options by an additional factor of 16. Incorporating both improvements into our ZFN platform resulted in an overall 64-fold increase in the number of ZFN design options available for efficient genome editing at any target cleavage site.
  • The manuscript also highlights preclinical studies performed using the new ZFN architectures, which demonstrate a high degree of precision, efficiency, and specificity across three therapeutic applications. These modifications along with several other improvements have been incorporated into Sangamo's second generation ZFN platform technology.

Is general: Yes