Naked DNA--the poor man's gene therapy?

• Published in: Gene therapy Vol. 5; no. 5; pp. 573 - 574
• Main Author: Moelling, K
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.1998
• Subjects: Animals; Antigen-Presenting Cells - immunology; Cytokines - immunology; DNA - immunology; Gene therapy; Genetic Therapy; Humans; Mice; Vaccines, DNA - immunology
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3300673

Vaccination with naked DNA was originally designed as a control experiment to test liposomes as DNA carriers. It proved to be a surprise that DNA alone was more effective in provoking an immune response than DNA packaged with liposomes. This was the first of many surprises about naked DNA. DNA, when injected intramuscularly, is taken up by some kind of cell, is transcribed into the actual mRNA and translated into protein antigens. Thus, the vaccine is produced by the vaccinee himself. The plasmid DNA contains, besides the appropriate gene, promoter-enhancer signals, for example, the immediate-early promoter of cytomegalovirus. The DNA vaccine mimics a natural infection or a live-attenuated vaccine. While such vaccines are not without risk, a DNA vaccine can be tailor-made avoiding any dangerous or undesired sequences, for example, sequences which favor integration of the DNA into the host chromosome such as long terminal repeats (LTRs) of HIV, or genes required for replication. Antigens, when expressed intracellularly, induce preferentially a cellular immune response and activate cytotoxic T lymphocytes (CTLs) by presentation of peptides from the inside of the cell. Peptide vaccines, in contrast, preferentially activate a humoral response.