Harrison's Internal Medicine Chapter 65. Gene Therapy in Clinical Medicine Gene Therapy in Clinical Medicine: Introduction Gene transfer is a novel area of therapeutics in which the active agent is a nucleic acid sequence rather than a protein or small molecule. Because delivery of naked DNA or RNA to a cell is an inefficient process, most gene transfer is carried out using a vector, or gene delivery vehicle. These vehicles have generally been engineered from viruses by deleting some or all of the viral genome and replacing it with the therapeutic gene of interest under the control of a suitable. | Chapter 065. Gene Therapy in Clinical Medicine Part 1 Harrison s Internal Medicine Chapter 65. Gene Therapy in Clinical Medicine Gene Therapy in Clinical Medicine Introduction Gene transfer is a novel area of therapeutics in which the active agent is a nucleic acid sequence rather than a protein or small molecule. Because delivery of naked DNA or RNA to a cell is an inefficient process most gene transfer is carried out using a vector or gene delivery vehicle. These vehicles have generally been engineered from viruses by deleting some or all of the viral genome and replacing it with the therapeutic gene of interest under the control of a suitable promoter Table 65-1 . Gene transfer strategies can be described in terms of three essential elements 1 a vector 2 a gene to be delivered and 3 a relevant target cell to which the DNA or RNA is delivered. The series of steps in which the donated DNA enters the target cell and begins expression is referred to as transduction. Gene delivery can take place in vivo in which the vector is directly injected into the patient or in the case of hematopoietic and some other target cells ex vivo with removal of the target cells from the patient followed by return of the modified autologous cells after gene transfer in the laboratory. The latter approach offers opportunities to integrate gene transfer techniques with cellular therapies Chap. 67 . Table 65-1 Characteristics of Gene Delivery Vehicles Viral Vectors Features Retroviral Lentiviral Adenoviral AAV Hun Foamy Vir Viral genome RNA RNA DNA DNA RN Cell division Yes G1 phase No No No Viral Vectors Features Retroviral Lentiviral Adenoviral AAV Hun Foamy Vir requirement Packaging limitation 8 kb 8 kb 8-30 kb 5 kb 1 Immune responses to vector Few Few Extensive Few Few Genome integration Yes Yes Poor Poor Yes Longterm expression Yes Yes No Yes Yes Main Persistent Persistent Highly Elicits .
