Nucleic acids therapies

Limitations of conventional drag delivery systems are particularly acute for the new biotherapeutics, such as peptide and protein drugs and nucleic acid therapies. 

Early development of nucleic acid therapy was aimed at genetic deficiency diseases which were amenable to replacement therapy, or correction by administration of the protein products of the defective genes, as described in Chapter 3. The introduction of the normal counterpart of a defective gene into cells of the patient, resulting in the long-term production of the missing protein, appeared as a desirable alternative to the repeated parenteral administration of purified protein (Verma, 1990 Caskey, 1992). However, the current span of nucleic acid-based therapies far exceeds this limited application conceived initially (Riordan and Martin, 1991 Crooke, 1992a). 

Somatic nucleic acid therapies may be performed by two methods. Nucleic acids can be delivered into the desired cells by the direct administration of genes or oligonucleotides to the patient in the clinic. This approach is termed in vivo gene therapy. Alternatively, genes may be introduced in the laboratory into cells obtained from the patient or from other suitable sources, and the recipient cells selected for desired characteristics may be reintroduced into the patient. This approach is known as ex vivo gene therapy. 

The use of nucleic acids as therapeutics is an unprecedented concept, and therefore the regulatory guidelines have evolved simultaneously with the technologies, and continue to do so. Because gene therapy using retroviral vectors is the most advanced of the nucleic acid therapies, regulatory issues and concepts are relatively better formulated in this area (Walters, 1991 FDA Report, 1991). 

Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS, Wickstrom, E., Ed. Wiley-Liss New York, 1991. 

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