Lentigen's LentiMax™ vectors have been designed to maximize their biosafety features, which include:

• A deletion in the enhancer of the U3 region of 3'LTR ensures self-inactivation of the lentiviral construct after transduction and integration into genomic DNA of target cells
• Lack of accessory genes in the lentiviral vector manufacturing process
• The vector and helper constructs contain no significant areas of homology, minimizing their chance for recombination
• None of the HIV-1 genes (gag, pol, rev) will be expressed in transduced cells, as they are expressed from packaging plasmids lacking packaging signal. Therefore, the lentiviral particles that are generated are replication-incompetent
• Lentiviral vector particles will carry only a copy of your gene or gene silencing sequence of interest

Lentiviral vectors have been used in hundreds of laboratories around the world without incident. Whenever conducting experiments using lentiviral vectors, it is recommended that they be performed under standard Biosafety Level 2 (BSL-2) laminar flow hood. Details on requirements for creating a BSL-2 work environment are available in the U.S. Department of Health and Human Services publication Biosafety in Microbiological & Biomedical Laboratories, 4th edition.

Lentiviral vectors are currently being evaluated in at least five clinical trials. To date, lentiviral vectors have been shown to be safe when introduced into humans, as no adverse events have been reported (Dropulic and June, 2006).

Lentiviral vectors have a distinct safety advantage over traditionally used Murine Leukemia Virus (MuLV) Retroviral Vectors. MuLVs have caused insertional oncogenesis in human clinical trials. In contrast, lentiviral vectors have several distinct safety advantages over MuLV vectors:

• Lentiviral vectors are not known to cause oncogenesis (i.e., show signs of genotoxicity), in contrast to MuLVs
• The lentiviral vector Long Terminal Repeats (LTR) do not contain highly active transcriptional enhancers, rather amplify mRNA expression by the Tat protein binding to the TAR element, facilitating elongation of mRNA. The highly active transcriptional enhancers of MuLV vectors are believed to be one of the factors involved in oncogenic genotoxicity resulting from insertional mutagenesis
• The self-inactivating nature of LentiMax™ vector increases their safety
• There are 40 million people infected with the AIDS virus, a lentivirus. Even though this represents billions of integration events, including events in patients which contain disease progression by anti-retroviral drug therapy, there is not a single documented case of oncogenesis due to an integration event by a Lentivirus
• Recent studies in mice have shown that while MuLV vectors are genotoxic (due to insertional mutagenesis), lentiviral vectors show no such genotoxicity (Montini, et. al., Nature Biotechnology, 2006)

Dropulic, Current Hematology Reports, 2005 [pdf]
Dropulic and June, Human Gene Therapy, June 2006 [pdf]
Montini et. al., Nature Biotechnology, June 2006 [pdf]