"Naked" DNA




Integrates gene into host chromosomes, offering chances for long-term stability

Most do not cause serious disease; large capacity for foreign genes

Integrates genes into host chromosomes; cause no known human diseases

Have no viral genes, so do not cause disease

Same as for liposomes; expected to be useful for vaccination


Drawbacks of Existing Vectors

Genes integrate randomly, so might disrupt host genes; many in feet only dividing colls

Genes may function transiently, owing to lack of integration or to attack by the immune system

Small capacity for foreign genes

Less efficient than viruses at transferring genes to cells

Inefficient at gene transfer; unstable in most tissues of the body

Figure 1 Schematic: example drawing of a few gene delivery vectors. A. Retrovirus, B. adenovirus, C. adeno-associated virus, D. liposomes, E. naked DNA. Polyplex not shown. (Reprinted from Ref. 295. Courtesy of Slim Films.)

to the nucleus. Many viral vectors, including Ad and AAV, can transduce most cells, including nondividing lung epithelial cells, while retroviruses target proliferating cells, such as tumors [27-29].

The AAV and retroviruses integrate their genomic material into the host genome, which carries the risk of activating oncogenes or deactivating tumor suppressor genes [29,30]. This risk must be weighed against the advantage of stable gene expression. Adenoviruses induce both a humoral and a cell-mediated immune response, making chronic therapy difficult [20-25].Viral vectors also have a DNA packing size limit; for example, AAV can accommodate ~ 4kilobase (kb) pairs of DNA [5]. The coding region of the CFTR gene (4.5 kb) narrowly makes the size cutoff of many viral vectors, limiting potentially beneficial modifications to the gene expression system. Modifications aimed to make viral vectors safer also may reduce the DNA packaging limit [5]. To address this potential shortcoming, the CFTR gene has been spliced into multiple parts and delivered in multiple vectors [31-34]. Finally, it is noteworthy that viral vectors have exhibited reduced efficiency following nebulization [35-38]. Even with these limitations, viral vectors will remain the predominant mode of gene delivery in the lung until the efficiency of synthetic systems is significantly improved. For recent reviews of viral gene therapy, see Refs. 39-41.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book

Post a comment