Realizing the Promise of Gene Therapy: Successes, Setbacks and Challenges    Methods Currently Employed Identifying a disease that is likely to respond to gene therapy Isolating a functional copy of the gene Incorporating the gene into a carrier (vector) Delivering the gene Incorporating the Gene into a Chromosome Determining whether the gene product is produced  Partial Successes and Ongoing Trials Gene Therapy for Severe Combined Immune Deficiency (SCID) Gene Therapy for Cystic Fibrosis Gene Therapy for Canavan Disease  Setbacks Insufficient Numbers of Cells Producing the Gene Product (Andrew Gobea’s therapy for SCID) Immune Reactions Targeting Cells Carrying the Vector (death of Jesse Gelsinger after therapy for Ornithine  Transcarbamylase Deficiency [OTC]) Inadvertent Activation of Cancer-Causing Genes by a Vector (development of leukemia in French patients treated for SCID) Challenges Safe and Effective Delivery of the Gene Production of a sufficient amount of gene product Achieving a lasting improvement for the patient Future Approaches Controlling the chromosomal region where the delivered gene is inserted Targeting specific sites on chromosomes for gene integration Preventing insertion near cancer-causing genes by using insulators Alternate Delivery Methods to Avoid Complications with Vectors Liposomes containing genes without the need for vectors Nanoparticles packaging DNA molecules for entry through nuclear pores Expanding the means for achieving the goals of gene therapy by exploring alternative ways to assist the cell in producing the functional gene product or blocking the formation of a harmful product Correction of the patient’s DNA Regulating production of the gene product by methods that affect RNA       RNA interference leading to degradation of specific RNAs Antisense RNA preventing protein production Correction of RNA, through control of splicing