天美传媒

Donald B. Kohn, M.D., studies the biology of blood stem cells, which are located in the bone marrow and have two important properties: they can duplicate themselves and they can create all types of blood cells. Over the course of 30 years of research, Kohn has developed new clinical methods to treat genetic blood diseases using blood stem cells that have been modified to remove genetic mutations.

Kohn鈥檚 blood stem cell gene therapy method collects some of a patient鈥檚 own blood stem cells and either adds a good copy of the defective gene or fixes the broken genes to eliminate disease-causing mutations. The patient then receives a transplant of their own corrected stem cells, which will ideally create an ongoing supply of healthy blood cells. Importantly, this method eliminates the risk of rejection associated with receiving a bone marrow transplant from a different person, meaning the patient doesn鈥檛 have to take a lifelong supply of anti-rejection drugs. 

Kohn鈥檚 clinical trials for adenosine deaminase-deficient severe combined immunodeficiency (also known as ADA-SCID or bubble baby disease), a condition where babies are born without an immune system and often don鈥檛 survive past the first two years of life, have cured more than 40 babies to date. Babies with the condition and their families have traveled to UCLA for this life-saving treatment from as far away as Lebanon and a new company was formed in 2016 to further develop the therapy and make it available at other centers and to more patients. 

Kohn is now applying similar blood stem cell gene therapy techniques in clinical trials for two other diseases. One of these diseases is X-linked chronic granulomatous disease, a rare inherited immunodeficiency disorder that prevents white blood cells from effectively killing foreign invaders such as bacteria, fungi or other microorganisms. If untreated, patients often succumb to chronic granulomatous disease within the first decades of life. 

The second disease is sickle cell disease, the most common inherited blood disorder in the United States. This disease causes abnormal 鈥榮ickle-shaped鈥� red blood cells that block small blood vessels and do not provide the appropriate amount of oxygen to the body, resulting in debilitating pain and organ damage. Kohn鈥檚 clinical trial seeks to overcome or repair the genetic mutation that causes this devastating disease, which impacts millions worldwide. 

Kohn earned his bachelor鈥檚 and master鈥檚 degrees from the University of Illinois, Champaign-Urbana and his medical degree from the University of Wisconsin School Of Medicine. He completed a pediatric internship and residency in Wisconsin followed by a medical staff fellowship in the Lymphoid Malignancies Branch (formerly the Metabolism Branch) of the National Cancer Institute.

Kohn began working on gene therapy as a fellow at the National Institutes of Health in 1985 and then began practicing as a pediatric bone marrow transplant physician at Children鈥檚 Hospital Los Angeles in 1987.  While practicing at Children鈥檚 Hospital Los Angeles, he started his own lab focused on stem cell research and has continued this work, advancing new therapies from the lab to the clinic. 

Eric B. Kmiec, Ph.D., is well known for his pioneering work in the fields of molecular medicine and gene editing. Since 2014 he has directed the Gene Editing Institute of the Helen F. Graham Cancer Center & Research Institute at Christiana Care Health System.

Under Dr. Kmiec鈥檚 leadership, the Gene Editing Institute has become a leader in gene editing and biomedical research in cancer and other inherited disease. It is the only institute of its kind embedded in a community cancer center where interactions among oncologists, genetic counselors and patients take place. This unique collaboration brings translational cancer research 鈥� from innovative basic science directly to patient treatment 鈥� to an entirely new level.

Throughout his professional career, Dr. Kmiec has led research teams studying the reaction mechanics, biochemistry and molecular genetics of gene editing in human cells. His early work with sickle cell disease led to research and development of the next generation of gene editing tools, including CRISPRs (clustered regularly interspaced short palindromic repeats) and to even more promising variations such as single-stranded DNA oligonucleotides (ssODNs) for the treatment of inherited disorders.

In April 2018, the team announced a major new development in the CRISPR Journal of the first CRISPR gene-editing tool to allow DNA repairs outside the human cell. The new 鈥渃ell free鈥� technology uses a protein called Cpf1 or Cas12a, that allows researchers to make multiple edits to DNA samples quickly and more precisely in vitro, that is, in a test tube or petri dish. This capability has generated unprecedented excitement about developing different CRISPR tools that could produce breakthrough treatments for a wide range of diseases by repairing a damaged gene, modifying it or deleting it entirely.

Thanks to a $1 million grant from the National Science Foundation in 2017, the Gene Editing Institute is collaborating with Delaware Technical Community College to develop the first-ever gene editing curriculum for community college students in Delaware and across the nation.

Collaborations with public and private partners are working to accelerate the drive to personalized cancer care. They include an agreement in 2017 with Israeli-based NovellusDx that leverages innovative gene editing technology to find gene mutations amenable to customized gene editing treatments for cancer patients, as well as efforts to commercialize an automated chip-based platform for the latest CRISPR/Cpf1 system for use in cancer diagnostics.

In 2016, Dr. Kmeic and colleagues at The Gene Editing Institute described in the journal, Scientific Reports, how they combined CRISPR with short strands of synthetic DNA to greatly enhance the precision and reliability of the CRISPR gene editing technique. The new tool, called EXACT (excision and corrective therapy) serves as both a template and a bandage for repairing a malfunctioning gene.

To accelerate breakthrough cancer research in the human genome, the Gene Editing Institute entered into an agreement with The Wistar Institute in 2016. This partnership integrates the Gene Editing Institute into Wistar鈥檚 Molecular Screening Facility, which will allow its innovative gene editing technologies to be made available to research projects at Wistar and to external users.

Dr. Kmiec is the recipient of multiple research awards from the National Institutes of Health (RO1s, R21s), the American Cancer Society, the Binational Industrial Research and Development (BIRD) Foundation and other private foundations including the 2012 Proudford Foundation Unsung Hero Award in Sickle Cell Disease. He has been a member of numerous editorial boards, NIH study sections and review boards and is the (primary or corresponding) author of more than 155 scientific publications (mostly in genetic recombination and gene editing).

He holds 18 issued patents, most of which have been licensed by biotechnology and pharmaceutical companies and has founded two biotechnology companies. He is a senior scientific advisor and SAB member of ETAGEN, a gene editing company located in Cambridge, Massachusetts, centered on the development of therapeutic uses of gene editing.

Dr. Kmiec has been the primary mentor for 18 Ph.D. students and 4 MS students, all of whom have attained scientific positions. He has held or holds major administrative posts on various NIH regional and state biomedical research grants, including IDeA Network of Biomedical Research (INBRE) and Centers of Biomedical Research Excellence (COBRE). Dr. Kmiec was also honored as the Eminent Scholar in residence at Marshall University (Huntington, West Virginia) in 2009-2011 and was elected as an Honorary Commander of the 436th Air Wing at Dover Air Force Base in Dover, Delaware for in 2013 and again in 2014.

Dr. Kmiec earned his B.A. from Rutgers University, his M.S. from Southern Illinois University and his Ph.D. from the University of Florida School of Medicine.