The Israeli National Knowledge Center
for Gene Therapy (INKCGT)
Israeli Ministry of Science
the Goldyne Savad Institute of Gene Therapy:
"Supporting your endeavors by providing you
the needed tools for gene therapy projects"
The concept of using genes as therapeutic platforms emerged during the mid 20th century, and during the 1990's the first regulated registered studies were performed in the United States. Since then, over 7,000 patients have been treated in more than 1,000 reported studies spanning 15 countries across all continents, using various modalities of gene therapy for a variety of different diseases (http://www.wiley.co.uk/genmed/clinical/).
As of August 2005, a total of 725 studies were in the process of or have been reviewed by the recombinant DNA Advisory Committee (RAC) of the National Institutes of Health of the United States (http://www4.od.nih.gov/oba/rac/aboutrdagt.htm).
About 40 studies have been performed for tracking of gene delivery and over 660 for therapeutic assessments. Sixty studies were for monogenic diseases and 470 for cancer, which is also the most common disease category for gene therapy studies worldwide. Two gene therapy agents are currently available in the market: Fomivirsen, an anti-sense construct for the treatment of cytomegalovirus retinitis in AIDS patients, and the p53 tumor suppressor coding sequence in an adenovirus vector for the treatment of head and neck cancer patients (this therapy is only registered in China). A large proportion of patients who participated in the first gene therapy clinical trials, were administered marker genes rather than therapeutic genes. Two deaths have been attributed directly to gene therapy, out of the thousands treated. These mortality statistics attributed to gene therapy are indeed very low, in comparison to mortality statistics associated with chemotherapy and transplantation, two therapeutic modalities frequently used today in clinical practice for disease targets of gene therapy.
The art of drug development, based on the of hgenetic makeup umans or their pathogens, is based on a rational design and combinatorial approaches for the selection of the specific genetic material to be used and the preferred gene delivery methods that will be compatible with the human anatomical, physiological, biochemical, molecular characteristics and ethical standards. In Israel, a number of gene therapy studies have been performed, and many pre-clinical trials are currently being conducted. Investigators report their progress at the annual Israeli Gene Therapy Society (ISGT) meetings. This year (2007), the 5th annual meeting will take place on April 17th at the Faculty of Medicine, Technion IIT, Haifa, Rappaport Hall. Relevant information and program of lectures and speakers are posted at the ISGT web site: www.isgt.org.il .
The goal of the INKCGT is to support and motivate researchers in Israel in their investigations and studies relating to gene therapy through funding from the Israeli Ministry of Science. Our approach is to provide researchers with tools that will help them overcome the major obstacles that have been identified in this process. In order to reach clinical trials in humans, the stages that need to be overcome include the initial assessment in vitro, later, in vivo in animal models, then evaluation for toxicity, culminating in the production of a drug which is tested in human subjects. In an effort to disseminate knowledge to all the scientific/medical community, and to facilitate the progress of gene therapy projects in the country, we have established the following service units:
Viral Vector Construction Unit.: The aim of this unit is to help investigators build their viral vectors. In addition, we provide knowledge and support with naked DNA delivery methods such as hydrodynamic injections, electroporation and, in the future, laser beam gene transfer system. In this unit, our aim is to provide support through relevant materials, and also further training on the bench and in protocol design.
Imaging Unit :
The aim of this unit is to help investigators assess the effectiveness of their delivery systems. In this unit, we regularly provide three types of imaging tools: A - the CCCD system to monitor luciferase expression. B – the GFP detection camera to monitor GFP expression; and C – the Cell Vizio system to detect low level expression and single cell expression of fluorescently expressed proteins in vivo. In addition, in specific cases, we can also assist with fMRI monitoring and imaging in conjunction with the HBRC center at Hadassah University Hospital, headed by Roland Hesch, and with the support of Gadi Goelman and Rinat Abramovitz. In addition, we can also provide assistance in ultrasound imaging in conjunction with the Radiology Department.
Pharmacogenomic Unit.: The objective of this unit is to tailor the preferred regulatory elements to each specific expression system to be used in gene therapy. This is performed by determining which genes are highly expressed, as assessed by tailor-made macroarray platforms. For any given gene therapy project, the suggested promoter and enhancers are selected using this pharmacogenomic/bioinformatics tool.
GMP Production Rooms.: We provide GMP production rooms for those investigators who wish to produce their delivery systems in a standard and approved environment staffed by investigators knowledgeable in the GMP production of biologicals. This unit will also provide technical support to investigators in drafting their standard operation procedures (SOPs), and in performing their study.
It is important to stress that the above mentioned service units support both the scientific/medical institutions in Israel and the biotechnology and pharmacological industries in the country.