Title: Molecular and Tissue Engineering
Funder: Department of Health (England)

Abstract: The main aim of this research programme is to develop new therapies for NHS priority areas by exploiting recent advances in molecular and tissue engineering. Molecular engineering, also referred to as gene therapy, involves the introduction of genes into a target cell, with the aim of restoring, modifying or enhancing the cell’s function. Similarly, tissue engineering seeks to create substitute tissues and organs for the human body, to repair or replace those whose function is lost through illness, injury, or aging. Therefore, an important advantage of molecular and tissue engineering over current therapies is that they have the potential to cure disease through replacement of malfunctioning genes or tissues, which is a significant evolution in medical treatment. Molecular and tissue engineering have gradually begun to make a significant impact on medical practice. The availability of bioengineered skin products and tissue-engineered cartilage from the NHSBT Tissue Services, which is the UK's major provider of human tissue, has substantially changed the way chronic wounds and damaged joints are treated. Our colleagues at the UCL Institute of Child Health have shown that a functional immune system can be restored in babies with life threatening Severe Combined Immunodeficiency (SCID, also known as bubble baby syndrome), following replacement of a defective gene with a normal functioning copy. Similarly, a patient with an inherited eye disease with no effective treatment (Leber’s congenital amaurosis), benefited from improved vision following gene transfer in a clinical trial that was conducted at the UCL Institute of Ophthalmology and Moorfields Eye Hospital. Several new strategies are currently being developed by scientists in the NHSBT and associated centres of excellence that address some of the challenges that remain in these emerging specialties. In aim 1, new safer vectors are being developed that enable the delivery of larger genes to target cells, thereby creating treatment opportunities for a large number of inherited disorders such as haemophilia and cystic fibrosis. In specific aim 2, we propose to modify cells of the immune system to enable them to better target and then destroy cancer cells that are widely distributed in the body. Aim 3 takes advantage of a new method to derive a type of stem cell, called induced pluripotent stem cells (iPS). These cells can be obtained from normal adult tissues such as the skin and appear to be Page 9 of 35 as potent as those derived from embryos but obtained without destroying embryos or eggs. They therefore have the potential to form any tissue. But methods for isolation and manipulation of these cells under strict processing conditions need to be defined to ensure their suitability for clinical use, which is the focus of aim 3. Once derived these clinical grade iPS cells will be used for the treatment of age related macular degeneration (AMD), a disease that is currently incurable. Finally, in aim 4 we develop methods to improve the blood supply and supporting structure for cells involved in the process of tissue repair so that they remain fully functional and are able to generate viable tissue. At least four new therapeutic products will emerge through the course of this research that may impact on a range of diseases, with significant benefit to the NHS. The NHSBT is probably the only academic institution in the UK that can engage in such a programme because: (1) it has extensive in-house expertise in the isolation of cells, tissue engineering and gene transfer, and (2) it has developed a network of clean rooms that enable manipulation of cellular and gene therapy products in a controlled environment, which is required for their use in humans. Furthermore, strong, international, interdisciplinary, multiinstitution partnerships with key experts already exist, thus ensuring that the goals of this programme are achieved in a timely manner.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: EYE;CANCER AND NEOPLASMS;BLOOD;CONGENITAL DISORDERS