Gene Editing Institute Christiana Care

Genome customization is now one of the most exciting, innovative, and quickly evolving areas of biomedical research. With the emergence of new technologies including TALENs and CRISPR/Cas9, mammalian genome editing is within the technical capabilities of the vast majority of skilled scientists. But, deploying the gene editing process is fraught with significant challenges and even the most skilled practitioners must rely on and benefit from proper planning and support to ensure that their experimental approach has a reasonable chance of success.

After 25 years as a pioneering group in the field of genome editing, the Kmiec laboratory has formed the Gene Editing Institute (GEI) and will remain located at the center for translational cancer research within the Helen F Graham Cancer Center. GEI evolved from a genome customization core managed by Eric B. Kmiec, Ph.D. and has already contributed to the development of these technologies with publications in Nature: Scientific Reports and in PLOS ONE in 2014 and 2015. The Gene Editing Institute is now on the cutting edge of genomic research, both as a research for discovery investigations and as a research for undergraduate and graduate education. For research applications, we can analyze mutagenesis in the human genome as a function of normal cell processes or help evaluate drug action by creating tools to alter specific genes within the mammalian genome. GEI's approach is to directly consult with research groups in the design, synthesis and optimization of gene editing tools that can be used across a wide array of biomedical applications. While these cutting edge tools are available for purchase, personal collaboration addressing the true capabilities of the technologies and advice on whether they will meet the researchers' goals are not readily accessible commercially. For educational opportunities, we provide group or individual tutorials on the concepts of gene editing and aid in the experimental design of genetic tools for researchers interested in employing gene editing.

Research Applications

TALEN therapeutics: Scientists evaluating various drugs or molecular treatments often target a particular protein or gene function by utilizing TALENs to disrupt or modify that function in a targeted pathway. These changes in gene expression, for example, broaden the scope of evaluation in studies aimed at discovering the response of cancer cells to action of a new drug. Functional genomics is enabled in an easy fashion, so much so that many research groups can now carry out functional genomic studies within their own laboratories.

TALENs for progenitor/stem cells: Researchers interested in the analysis of stem cells/progenitor cell development and function, order and use our TALENs to alter gene expression patterns that lead to differential, differentiation of certain kinds of cell populations.

TALEs for gene knockdown/gene up regulation: Scientists are using our TALEs (the binding components of the TALEN) to regulate gene expression at the level of DNA. This approach is an extremely efficient way to modulate the levels of gene expression both in cell and animal models. It is particularly efficient in lower eukaryotes such as C. elegans.

Epigenetic TALEs: We are currently developing an innovative strategy to combine the DNA specific binding capacity of the TALE with enzymatic domains such as TET demethylase in order to demethylate very specific sites within promoter regions, an approach that will define the importance of epigenetic markers leading to oncogene expression and changing DNA function.

CRISPR/Cas9 systems I: Scientists interested in creating pure knockouts in cells have engaged us to design and create these systems for them. While clearly easier to make and to produce, CRISPRs are much less specific in their activity profiles than TALENs and often create serious mutagenesis within the genome at random sites. Thus, the design of these CRISPRs is critical and our workshops are proving invaluable to researchers who are evaluating use of this technology. In a new exciting and innovative approach with collaborators, we will help combine the Flox/insertion system with CRISPR technologies to create an insertion/ deletion model so that random genes can be swapped in and out of the genome at chromos specific designated sites within a chromosome. This collaboration could lead to a significant advancement in the technology that could then be offered as a new tool for other clients.

CRISPR/Cas9 systems II: This system is quickly developing as the most popular genome modifier due to its simplicity of design and cloning. Indeed, CRISPR/Cas9 can catalyze all of the actives of TALENs, but with the important caveats described above. With these drawbacks in mind, we tailor the approach for each application and advise our clients as to which tool is most appropriate not only to use, but why it will sidestep the collateral effects. CRISPRs can also be used in epigenetic editing, the next wave of genome modification, and an area in which we are actively engaged.

Educational Applications

We are partnering now with a biotechnology company to develop and produce an undergraduate and graduate student, hands-on instructional laboratory exercise for gene editing. We are in the process of writing an educational module to complement a gene editing kit for laboratory classes in molecular biology, genetics or biotechnology, etc. The kit will contain all of the cells and reagents needed to perform simple gene editing and we will provide a video and/or on-site instruction to the students. The basis of this kit is founded in over 20 years of research and development of a well accepted and well-established gene editing model system developed by the Kmiec laboratory. We are arranging to beta test the kits at several universities. This would be a first for an IDeA state core /institute facility and meets the goals of these programs in establishing more translational and educational work with the biotechnology community, product development and entrepreneurship.

The Gene Editing Institute was selected to present two workshops at prime speaking slots at NISBRE in June 2014. The feedback was overwhelmingly positive and we have been busy ever since responding to inquiries on use of these technologies, producing reagents and providing technical support. We are currently engaged in developing CRISPR and TALENs for multiple clients including the University of Delaware, University of North Dakota, Dartmouth University, Wistar Institute, University of Vermont, and the Mayo Clinic.

This positive response also led to the creation of "Precision in Practice: Success with Gene Editing Technologies" instructional workshops as outlined in the attached brochure. We have already provided a number of workshops and personal consultations, the most amazing and wonderful experience was at the University of North Dakota, where our staff spent two days presenting workshops and meeting with 10 clients, most of whom are now fully engaged with us in production of reagents for their research. Our educational offerings have expanded from simple teleconferences to full-day on-site workshops and multi-day client-site workshops and one-on-one consultations. We expect this trend to continue as it is far more cost-effective for institutions to host workshops with 10 to 12 researchers at their location.

A Delware INBRE Core Facility

Address

Helen F. Graham Cancer Center & Research Institute
4701 Ogletown Stanton Road
Newark, DE 19713

Personnel

Eric B. Kmiec, Dr.
Director


eric@geneeditinginstitute.com

Services

  1. We produce custom-made gene editing tools and reagents for clients from INBRE and COBRE-affiliated institutions, as well as other outside clients. Revenue will be applied to cover the cost of supplies used in the creation of these reagents.
  2. We conduct popular instructional workshops, one-on-one consultations, webinars and seminars to provide training in design and experimental plans in-house and at client locations throughout the national INBRE/COBRE network and beyond.
  3. We provide in-house training for undergraduates and graduate students on a case-by-case basis. Emphasis will be placed on the INBRE summer scholar and similar programs. We envision this becoming a national program utilized by member institutions within the INBRE/COBRE network, for example, the University of Vermont has engaged us through their COBRE program. We will extend our services to other IDeA state programs such as CTSA, etc.
  4. We operate as a full training resource facilities for faculty, undergraduate and graduate students providing instruction and advice in the technologies associated with genome editing and genetic engineering. GEI will also provide technical support for internal and external investigators struggling with implementation of these technologies in their own labs.
  5. Due to the nature of designer nucleases, not every construct is equally active. Because of this, we also offer construct activity validation services. We will test construct activity in either a human or mouse cell line through the use of various assays which can detect cutting efficiency in the genome. This service is particularly valuable to those who will be using their designer nucleases in animal models, saving time and effort by ensuring a suitably active nuclease is used.