Gene Therapy

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