Horizon Discovery Takes Exclusive License for Novel Transposon-Based Gene-Editing Technology Platform

Horizon Discovery Group plc recently announced the completion of licensing agreements with all joint patent holders to provide exclusive worldwide rights to a novel transposon-based gene-editing technology platform.

The license broadens Horizon’s gene-editing capabilities, with immediate applications in biomanufacturing, diagnostics, and cell therapy. This release follows a May 2017 announcement describing Horizon gaining initial rights to this technology.

The gene-editing technology is based on a type of transposon (Helitrons), which uses a “copy-and-paste” mechanism to allow multiple copies of a DNA sequence to be incorporated into a genome, either immediately, or by reactivating the transposon machinery to increase the copy number at a later time. This is in contrast to current transposon technologies (eg, Sleeping Beauty or PiggyBac), which transfer DNA by a “cut-and-paste” mechanism, in which a sequence is removed from one part of a genome and randomly inserted elsewhere.

This technology also enables the highly efficient delivery of DNA into a genome. A common method for DNA delivery is through the use of retroviruses or lentiviruses, which can be challenging to manufacture and are covered by associated IP that require expensive licenses. The Helitron IP provides a far simpler and less-expensive approach to manufacturing, promising Horizon the opportunity to realize significant operational efficiencies in cell engineering, and cell and gene therapy.

The Helitron patent is held by four inventors: Zoltan Ivics (Max Delbrück Center for Molecular Medicine (MDC) and the Paul Ehrlich Institute), Ivana Grabundzija (MDC), Vladimir Kapitonov (Genetic Information Research Institute), and Tilmann Buerckstuemmer (Global Head of Innovation, Horizon Discovery). Horizon has now been granted an exclusive license from all co-owners for use of the technology, providing freedom to operate for all applications including tool development, service provision, and therapeutic development.

Applications of this technology for Horizon include:

-Biomanufacturing: supports delivery of the DNA sequence of the protein to be manufactured into bioproduction cell lines (eg, CHO), and holds the potential to enhance the productivity of cells by having multiple copies of the target sequence present.

-Diagnostics: to be used to efficiently develop reference standards for assays designed to measure the copy number of a gene (eg, Her2 in breast cancer).

-Therapeutics: provides an alternative mechanism to deliver a gene of interest into a genome, and opens up a potentially revolutionary approach to therapeutic development where multiple copies of an expressing gene can drive the effectiveness of therapy.

Cell and gene therapy represents a particularly large opportunity. In 2015, public and private companies raised almost £8 billion to support development programs in cell and gene therapy, and the market has been estimated to be worth up to £14 billion by 2025.

“At Horizon, we understand that the improvement of existing gene-editing technologies, as well as development of completely novel ones, is critical to our lasting success leading the way in the gene-editing space. Through the completion of gaining exclusive rights from all parties, Horizon now has access to a powerful new gene-editing platform that provides a unique approach to gene editing and DNA delivery, strengthening our capabilities in bioproduction and diagnostics, and for the first time directly as a cell or gene therapy,” said Dr. Darrin M Disley, Chief Executive Officer, Horizon Discovery Group.

Transposons, also called “jumping genes” are discrete pieces of DNA that are able to move from one site to another within one genome and function both as a driver of evolution by contributing to the formation of new genes, and serve to support certain regulatory functions in cells. Given their relatively simple design and inherent ability to move DNA, transposons have been widely adopted as genetic tools, primarily to help remove and integrate genetic sequences. The most commonly used transposon technologies for gene editing are Sleeping Beauty and PiggyBac, both of which use a cut/paste mechanism, in which a sequence is removed from where it sits and is then inserted randomly elsewhere in the genome. Poseida Therapeutics raised up to $30 million in December 2016 to exploit PiggyBac to develop novel CAR-T cell therapy and gene therapy approaches for amongst others Jannssen Pharmaceuticals.

Horizon Discovery Group plc is a world-leading gene-editing company that designs and engineers genetically modified cells and then applies them in research and clinical applications that advance human health.

Horizon’s core capabilities are built around its proprietary translational genomics platform, a highly precise and flexible suite of gene-editing tools (rAAV, ZFN, CRISPR, and Transposon) able to alter almost any gene sequence in human or mammalian cell-lines.

Horizon offers over 23,000 catalogue products and related research services, almost all of which are based on the generation and application of cell and animal models that accurately recapitulate the disease-causing genetic anomalies found in diseases like cancer. Horizon’s commercial offering has been adopted by over 1,600 unique research organizations in over 50 countries as well as in the company’s own R&D pipeline to support a greater understanding of the genetic drivers of disease and the development of molecular, cell, and gene therapies that can be prescribed on a personalized basis. For more information, visit www.horizondiscovery.com.