Next Generation Gene Therapy for Fanconi Anemia Disorder Using CRISPR-Cas9 Gene Editing Technology–-Does This Approach Open Doors for Treating Other Rare Diseases?

Guest expert: Jakub Tolar, M.D., Ph.D., Professor, Department of Pediatric Blood & Marrow Transplantation, Tulloch Chair in Stem Cell Biology, Genetics and Genomics; and Director, Stem Cell Institute at the University of Minnesota

29-Jul-2015 2:30 PM EDT

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NEWSWISE (July 29, 2015) - Fanconi anemia (FA) is a rare (1 in 160,000) pediatric, autosomal recessive (inherited) disease characterized by multiple physical abnormalities, organ defects, bone marrow failure, and a higher than normal risk of cancer. The average lifespan for people with FA is 20 to 30 years. As yet, no specific treatment is known that can halt or reverse the symptoms of FA. Could gene therapy, specifically gene editing technology called CRISPR-Cas9 signal hope for FA and other blood diseases?

CRISPR (clustered, regularly interspaced short palindromic repeats)-Cas9 (CRISPR associated protein 9) system is a powerful DNA editing that MIT Technology Review described as "the biggest biotech discovery of the century.” The technology has two basic components. One part is the Cas9 protein, which snips out a defective gene. This molecular scissors is steered to its genetic target by the second component, a single molecule of RNA. The hope now is that the technology’s ability in repairing the FANCC gene in human fibroblasts – work that the scientific team led by Jakub Tolar, M.D., Ph.D., a Professor, Department of Pediatric Blood & Marrow Transplantation, Tulloch Chair in Stem Cell Biology, Genetics and Genomics; and Director, Stem Cell Institute at the University of Minnesota is focused on. According to Dr. Tolar, “Aside from blood and marrow transplantation that carries a risk of significant side effects, there are no treatments available that can halt or reverse the symptoms of children with Fanconi anemia disorder. The major function of bone marrow is to produce new blood cells. In FA, a DNA mutation renders the FANCC gene nonfunctional. Loss of FANCC causes patient skeletal abnormalities and leads to bone marrow failure. Aside from bone marrow transplantation (BMT) there are no specific treatments known that can halt or reverse the symptoms of FA. Using the CRISPR-Cas9 gene-editing system to repair the FANCC gene in human fibroblasts from a Fanconi anemia patient, our AAV-based gene therapy studies have demonstrated significant and promising results.” Dr. Tolar’s work against FA was licensed by Abeona Therapeutics including the IP from the University of Minnesota to treat patients with Fanconi anemia (FA) disorder and other rare blood diseases.

Dr. Tolar can discuss the following:

  • What is Fanconi Anemia (FA) disorder?
  • What are the gaps in current treatments such as bone marrow transplants?
  • How does ABO-301 work to treat FA? What efficacy has been demonstrated to date? What are the next steps in making ABO-301 available to patients?
  • Would this research lead to other breakthroughs in blood diseases? If so, which ones are the best candidates?

About Jakub Tolar, M.D., Ph.D.: Dr. Tolar is a McKnight Professor of Pediatrics at the University of Minnesota in the Division of Blood and Marrow Transplantation, and an attending physician at the University of Minnesota Masonic Children’s Hospital. Dr. Tolar is trained both in basic science and in medicine. He received his MD from Charles University in Prague, Czech Republic, and his PhD in Molecular, Cellular, Developmental Biology and Genetics from the University of Minnesota. He completed a residency in Pediatrics and a fellowship in hematology/oncology and bone marrow transplantation at the University of Minnesota. He is board certified in Pediatric Hematology/Oncology. Dr. Tolar has been the Director of the Stem Cell Institute since 2013.

About Fanconi anemia (FA) disorder: Fanconi anemia is a rare (1 in 160,000) pediatric, autosomal recessive (inherited) disease characterized by multiple physical abnormalities, organ defects, bone marrow failure, and a higher than normal risk of cancer. The average lifespan for people with FA is 20 to 30 years. The major function of bone marrow is to produce new blood cells. In FA, a DNA mutation renders the FANCC gene nonfunctional. Loss of FANCC causes patient skeletal abnormalities and leads to bone marrow failure. Fanconi anemia patients also have much higher rates of hematological diseases, such as acute myeloid leukemia (AML) or tumors of the head, neck, skin, gastrointestinal system, or genital tract. The likelihood of developing one of these cancers in people with Fanconi anemia is between 10 and 30 percent. Aside from bone marrow transplantation (BMT) there are no specific treatments known that can halt or reverse the symptoms of FA. Repairing fibroblast cells in FA patients with a functional FANCC gene is the focus of our AAV-based gene therapy approach.

About CRISPR-Cas9: The CRISPR (clustered, regularly interspaced short palindromic repeats)-Cas9 (CRISPR associated protein 9) system, the newest genome editing approach, uses a protein-RNA complex composed of an enzyme known as Cas9 bound to a guide RNA molecule that has been designed to recognize a particular DNA sequence. The RNA molecules guide the Cas9 complex to the location in the genome that requires repair. CRISPR-Cas9 uniquely enables surgically efficient knock-out, knock-down or selective editing of defective genes in the context of their natural promoters, unlocking the potential to treat both recessive and dominant forms of genetic diseases. Most importantly, this approach has the potential to allow safer, more precise gene modification.

About Abeona:

Abeona Therapeutics, Inc. develops and delivers gene therapy and plasma-based products for severe and life-threatening rare diseases. Abeona’s lead programs are AB0-101 (AA9 NAGLU) and ABO-102 (scAAV9 SGHG), adeno-associated virus (AAV)-based gene therapies for Sanfilippo syndrome (MPS IIIA and IIIB) in collaboration with patient advocate groups, researchers and clinicians, anticipated to commence clinical trials in 2015. We are also developing ABO-201 (scAAV9 CLN3) gene therapy for juvenile Batten disease (JBD); and ABO-301 (AAV LK19 FANCC) for Fanconi anemia (FA) disorder using a novel CRISPR/Cas9-based gene editing approach to gene therapy program for rare blood diseases. In addition, we are also developing rare plasma protein therapies including SDF Alpha™ (alpha-1 protease inhibitor) for inherited COPD using our proprietary SDF™ (Salt Diafiltration) ethanol-free process. For more information, visit http://www.abeonatherapeutics.com.

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