Devising strategies to treat genetic diseases with cell penetrating peptides

Introduction
Treatment of genetic diseases is limited. Gene therapeutic approaches are an option. However many genetic diseases effect cells in many organs in the body. Thus, the gene must be inserted safely into all the effected cells. Terrific if it works. You walk into the clinic and get your gene therapy and are cured for ever. Today¿s approach is to try to supplement the protein that is defective with giving that protein in excess in the blood with modest effects and at incredible costs with poor benefit to the patient. Maybe gene therapy will work, but it will take time to implement. Protein therapy is life long and expensive. We have previously shown that we can substitute a defective gene product, a tumor suppressor by defining the molecular structure of the protein, predicting which parts are important by computer based modeling, constructing a peptide which we believe will replace the defective gene, coupling it to a fragment of the HIV virus inorder to allow it to penetrate cells, and shown that we have beneficial effects in the treatment of kidney cancer.

Project
The fifth line of investigation which is relatively new for our lab, addresses a central issue. A large number of children are afflicted with genetic diseases. How should these patients be treated. What is available in today¿s medicine is largely symptomatic if even that. Gene therapy may not necessarily be applicable in many of these cases, at least not in the way we think about gene therapy. This project focuses on one of the more common genetic disorders, namely cystic fibrosis. We have previously gained experience in constructing peptides with the ability to penetrate cells in living animals.

This project is basically the following. Using computer programs and the expertise at the department a potential peptide will be generated which is connected to a peptide which enhances cell penetration. This construct will be expressed in mammalian cells. It will then be tested on cells from cystic fibrosis patients and these cells will be screened in 96 well plates to evaluate if this peptide is effective. If this works it will lay a foundation for treating cystic fibrosis and many other genetic diseases.

This project I think would interest scientists whom want to learn about molecular modeling, peptide synthesis, high throughput screening, fundamental cell biological techniques. This is real detective work and will require a student whom is able to liason between the different players in the field whom are present at the biomedical center. This project is a shot in the dark, is relatively easy to test with regards to cystic fibrosis, has unique possibilities to succeed given the expertise and core facilities at BMC and would if iti work¿s be groundbreaking for offering definitve treatments for the large group of pediatric patients suffering from genetic diseases as well as contemplating treatment of common diseases of the adult.