1. Viruses as Vectors Any virus can potentially be used to express foreign genes Different viruses are better suited for different kinds of uses Integration may be important, such as in many gene therapy uses Larger viruses can express more and larger foreign genes but are more difficult to manipulate The cis-acting promoters for genome replication and packaging must be understood

2. Potential Uses of Viral Vectors Gene therapy to replace a missing or inadequate gene Cure of illness by expressing a reagent to, for example, kill cancer cells Immunization by expressing an antigen from a pathogen Expression of genes in cultured cells for scientific study

22. Gene Therapy--An Apparent Success Restenosis--reblockage of coronary arteries after they have been opened by coronary bypass surgery or angioplasty 13 patients with restenosis were injected in the heart with DNA encoding vascular endothelial growth factor, which promotes angiogenesis All 13 patients had improved heart function

23. Gene Therapy--A Partial Success SCID--Severe Combined ImmunoDefficiency--is often due to the failure to produce adenosine deaminase (ADA) The accumulation of adenosine is particularly toxic for T cells and both humoral antibody and CTL functions are abolished Treatments include bone marrow transplant (BMT) if a suitable donor can be found or injection of ADA 1-2 times/week 10 people have been treated with T cells that were infected ex vivo with retroviral vectors expressing ADA Most now express ADA but not enough to do away with the ADA injections

24. Gene Therapy--Another Apparent Success SCID XI, caused by lack of the  c subunit of the receptors for IL-2, -4, -7, -9, and -15, can be treated only by isolation in a sterile bubble followed by BMT, if a donor is available Stem cells from bone marrow from three infants with SCID XI were infected ex vivo with retrovirus expressing the missing gene and the cells reinfused into the donors The 3 infants produce T, B, and NK cells and are apparently healthy Long term followup will be required to determine if the cure is permanent They have been successfully received a number of childhood vaccinations

25. Gene Therapy--A Failure Jesse Gelsinger, a young volunteer in a gene therapy trial who had a moderate OTC defficiency, died on 17 Sept 1999 He had been injected in the liver with high concentrations of adenovirus that expressed OTC He apparently died of a massive immune response to the adenovirus vector Inability to produce ornithine transcarbamylase (OTC) is often lethal, but moderate deficiencies may be controlled by strict control of diet