Transferring genes

Viral vectors Gene transfer Gene therapy... 

Certain characteristics of skeletal muscle fibers are particularly relevant when considering the future of gene therapy in muscle diseases. Skeletal muscle fibers are large syncytia containing thousands of postmitotic myonuclei, each of which expresses the same set of genes. The postmitotic nature of the myonuclei implies that in mature muscle fibers, cell division cannot play a role in spreading the transferred gene to required locations (i.e., whole muscles). On the other hand, once... 

The fact that they have been well studied, display almost 100 per cent transduction efficacy in sensitive cells and that the transferred genes are usually subject to long-term, fairly high-level expression renders retroviruses powerful potential vectors. These advantages form the basis of their widespread use in this regard. 

The duration of expression of transferred genes can vary, and is usually transient Infection of permissive cells with wild-type adenovirus usually results in cell lysis Adenoviruses display a broad selectivity in the cell types they can infect... 

Mueller, G. M., McKenzie, L. R., Homanics, G. E., Watkins, S. C., Robbins, P. D. and Paul, H. S. Complementation of defective leucine decarboxylation in fibroblasts from a maple syrup urine disease patient by retrovirus-mediated gene transfer. Gene Ther. 2 461-468,1995. 

Gao X, Huang L. Cationic liposome-mediated gene transfer. Gene Ther 1995 2 710. 

The potential use of gene therapy has since expanded as conditions such as cancer, atherosclerosis, transplant operations, and infectious disease are now viewed as suitable targets for intervention. For example, HTV and parasitic infection (2-5). Furthermore, the ability to transfer genes into cell in vitro is also an important tool in the research of gene expression. 

Lipid components of liposomes must perform a number of functions. First, it is important that the DNA is packaged into a small particle to protect the DNA and condense it into a smaller particle compatible with cellular uptake. Next, the lipids must enable the transfection process, which involves three key stages cell attachment and uptake into the cell, endoso-mal escape, and then movement into the nucleus for the expression of the transferred gene (Fig. 1) (14). 

Many diseases, such as hereditary metabolic defects and tumors, can still not be adequately treated. About 10 years ago, projects were therefore initiated that aimed to treat diseases of this type by transferring genes into the affected cells (gene therapy). The illustration combines conceivable and already implemented approaches to gene therapy for metabolic defects (left) and tumors (right). None of these procedures has yet become established in clinical practice. 

An additional drawback with regard to retroviral-based vectors is the propensity of the transferred gene to integrate randomly into the chromosomes of the recipient cells. Integration of the transferred DNA in the middle of a gene whose product plays a critical role in the cell... 

Zaitsev, S.V., Haberland, A., Otto, A., Vorob ev, V.I., Haller, H., Bottger, M. (1997). HI and HMG17 extracted from calf thymus nuclei are efficient DNA carriers in gene transfer. Gene Ther., 4, 586-592. 

Three different methods have successfully been used to transfer genes into animals ... 

Tseng, H.C. Chen, C.W. A cloned ompR-like gene of Streptomyces livi-dans 66 suppresses defective melCl, a putative copper-transfer gene. Mol. Microbiol., 5, 1187-1196 (1991)... 

---