Module 1: Introduction

Lecture 1: Introduction (Part I)

    

Synthetic gene delivery systems rely on direct delivery of genetic message into a specific cell and involve injection of exposed DNA and encapsulation of DNA with liposomes (cationic lipids mixed with nucleic acids), and nanoparticles. Even though this method displays low toxicity and is formed in abundance, gene transfer in common is weak and often temporary. The synthetic gene delivery transfer vectors are also known as non-viral vectors. It is possible that the time to come may witness advanced gene therapy protocols for synthetic gene delivery systems based on the experiences from non viral vector systems.

Viral vector systems are established on replicating viruses with either RNA or DNA genomes that have the potential to deliver genetic message into the host cell. These vectors are either of integrating or of non-integrating type. Integrating viral vectors exhibit constant expression of the defective gene product. Overall, genomes of replicating viruses consist of coding regions and cis -acting regulatory elements. The coding sequences include the genetic message of the viral, structural and regulatory proteins and are needed for division of infectious viruses, whereas cis -acting sequences are important for wrapping of viral genomes and unification into the host cell. To generate a replication-defective viral vector, the coding domains of the virus are substituted by the genetic message of a therapeutic gene, leaving the cis -acting sequences intact.

Gene therapy offers promising approaches towards treating many incurable diseases. Many hurdles and challenges are there for a sustained gene therapy approach and scientists around the globe are working to increase the efficacy of gene delivery vectors.

Setback history:

 

Jesse Gelsinger an 18 year boy who was suffering from a genetic disorder of liver named ornithine transcarbamylase deficiency died on September 17 th , 1999 during a clinical trial of gene therapy. Gelsinger was treated at the University of Pennsylvania using adenovirus vector containing a corrected copy of the gene. His death was a great set back to the field of gene therapy.