Our Focus

Gene Editing

gene editing: the next frontier in gene therapy

Gene editing has generated a lot of excitement in academia and drug development. Its promise is two-fold: the unique ability to correct genetic mutations that may cause disease; and its utility in creating and controlling genetic information within patient cells. Emerging science suggests that permanently fixing or “editing” mutated cells, or creating safer and more potent cell-based products with this technology could provide curative, one-time treatments for patients suffering from a broad range of diseases.

In June 2014, we acquired Precision Genome Engineering Inc., or Pregenen, a company with a sophisticated, advanced gene editing technology platform and research team. Our integrated teams are expanding our discovery research efforts in this emerging field. We are testing homing endonuclease and megaTAL gene editing technologies in a variety of potential applications and disease areas, including hematology and oncology. Reprogrammed homing endonucleases and megaTALs are novel enzymes that provide a highly specific and efficient way to potentially treat a variety of diseases by silencing, editing or inserting genetic components into a cell.


Structural depiction of a homing endonuclease bound to its DNA target. Homing endonucleases are compact proteins able to wrap around and effectively ‘saddle’ DNA. When they identify a DNA sequence that fits into their pattern of amino acid chemistries, they are able to cleave that DNA sequence. Such DNA recognition chemistries can be reprogrammed by our protein engineers to operate on DNA target sequences of our choosing.

Homing endonucleases can be paired with TAL arrays – modular and therefore easily reprogrammable DNA recognition components – creating hybrid “megaTAL” proteins with advanced DNA recognition characteristics. megaTALs are the most efficient genome editing ‘machines’ yet devised, landing at and modifying their target sites with extreme precision and efficiency.

why megaTALs and homing endonucleases?

All the gene editing technologies currently being explored by the pharmaceutical industry, including zinc finger nucleases, CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR associated protein 9) and TALENs (transcription activator-like effector nucleases), share DNA recognition and DNA cutting functions. They all differ in specificity, size, ease of delivery, and the detailed biochemistry that underlies their DNA recognition, cleavage, and repair mechanisms. Homing endonucleases are the only monomeric, naturally occurring proteins to bind and cleave DNA in a highly sequenced specific fashion. megaTALs are fusion proteins that combine homing endonucleases with the modular DNA binding domains of TALENs, resulting in improved DNA sequence targeting and unparalleled gene editing efficiencies. Since these hybrid nucleases still cut DNA using homing endonuclease cleavage biochemistry, they engage DNA repair pathways in a manner distinct from all other gene editing nucleases. The compact format and ultra-efficient nature of our nucleases make them powerful tools in our ongoing effort to build advanced gene editing processes and products for a broad range of therapeutic applications.

putting gene editing to work

In collaboration with leading academic institutions, we are using our gene editing platform to potentially discover and develop new, more advanced versions of our current ex vivo gene therapy product candidates, and to explore expansions into new disease indications.

Our CAR T cell technology also brings gene editing tools to the immunotherapy field. Our homing endonuclease and megaTAL technology offer a number of additional options to manipulate the gene of a cancer patient’s T cells in hopes of further increasing the specificity of anti-tumor activity and potentially make them more potent. Specificity and potency are essential to the development of CAR T cell therapies for effectively treating solid tumor cancers such as breast, prostate and colon cancer.