Oncoretroviral vectors Advantages Disadvantages Efficient and stable gene transfer Transduction rates of up to 40% of HSCs in non-human primates Low rates of expression One or fewer copies of provirus per cell Sensitive to chromosomal position effects Sensitive to DNA repeats, introns High fidelity gene transfer due to intact integration and absence of chromosomal rearrangements Limits on the size of the therapeutic gene (< 7 kb) insert Extensive clinical experience suggests that they are generally safe Difficult to deliver in vivo due to low titers (<107 TU/ml) Safety concerns. Potential problems with insertional mutagenesis due to integration inside or near a proto-oncogene . Lentiviral vectors Advantages Disadvantages Efficient and stable gene transfer Transduction rates of up to 90% of HSCs High levels of transgene’s expression High titers (>108 TU/ml) Extensive clinical experience due to AIDS Sensitive to chromosomal position effects High fidelity gene transfer due to intact integration and absence of chromosomal rearrangements Limits on the size of the therapeutic gene (< 10 kb) insert Safety concerns. Potential problems with insertional mutagenesis due to integration inside or near a proto-oncogene . Adenoviral vectors Advantages Disadvantages High efficiency of gene transfer Delivery of many genome copies per target cell, that typically translates into very high expression Relatively large therapeutic genes (25-30 kb with the latest generation vectors) High fidelity of gene transfer Vector genomes are genetically stable Transfer and expression are transient Since adenoviruses are non-integrating viruses, the transgene expression typically lasts 1-2 months in non-dividing cells, while is much shorter in dividing cells In vivo administration The pre-existing immunity against adenoviruses in individuals may result in low levels of transgene delivery and expression Extensive clinical experience Vectors are immunogenic since the virus capsid and remaining viral proteins cause inflammation No issues with insertional mutagenesis Safety issues: Vectors are lethal at high doses and are highly infectious Adeno Associated Vectors (AAV) Advantages Disadvantages Highly efficient gene transfer Several genome copies per target cell Small transgenes (£ 4.7 kb) High fidelity gene transfer Vector genomes are genetically stable Stable expression in some settings Able to integrate into target cell genome Transfer and expression are not always stable as the virus does not always integrate Questionable tropism for HSC In vivo administration Frequently immunogenic Generally safe at doses tested The pre-existing immunity in individuals may result in low levels of transgene delivery and expression Safety concerns: Potential problems with insertional mutagenesis and small chromosomal rearrangements

Table 1: Advantages and disadvantages of gene therapy vectors.

Goto home»