Gutless adenovirus: last-generation adenovirus for gene therapy.
Last-generation adenovirus vectors, also called helper-dependent or gutless adenovirus, are very attractive for gene therapy because the associated in vivo immune response is highly reduced compared to first- and second-generation adenovirus vectors, while maintaining high transduction efficiency and tropism. Nowadays, gutless adenovirus is administered in different organs, such as the liver, muscle or the central nervous system achieving high-level and long-term transgene expression in rodents and primates. However, as devoid of all viral coding regions, gutless vectors require viral proteins supplied in trans by a helper virus. To remove contamination by a helper virus from the final preparation, different systems based on the excision of the helper-packaging signal have been generated. Among them, Cre-loxP system is mostly used, although contamination levels still are 0.1-1% too high to be used in clinical trials. Recently developed strategies to avoid/reduce helper contamination were reviewed.
Alba
R
R
Gene Therapy Laboratory, Department of Biochemistry and Molecular Biology, Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, Bellaterra, Spain.
Bosch
A
A
Chillon
M
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001709:Biotechnology / Q000379:methods; D002213:Capsid; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006378:Helper Viruses / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D011401:Promoter Regions, Genetic