What is Integration Defective Lentivirus (IDLV)?

Integration Defective Lentivirus (Integrase Deficient Lentivirus, or  Non-Integrating Lentivirus) is the Lentivirus lack of integration capacity. Pseudotyped lentivirus became the most effective research tool used to deliver gene products. However, for many applications, the genomic integration of Lentivirus brings in the risk of insertional mutagenesis. Therefore, the Integration Defective Lentivirus (IDLV) became an ideal solution, special in clinical and therapeutic applications.

How was the IDLV produced?

Pseudotyped lentivirus are produced by co-transfection the transfer plasmid (containing the gene products for delivery) with the packaging plasmids (which normally containing multiple plasmids). Lentivirus genomic integration is dependent upon the HIV-1 integrase which is part of the polyprotein precursor gag-pol.

To produce Integration Defective (or Deficient) lentivirus, different mutations were made in HIV-1 integrase (in one of the packaging plasmids). The best mutation was tested as the point mutation at D64V ^{[Ref. 1]}, which reduces 97% integration with limited reduction in the lentivirus transduction rate.  Gentarget constructed the IDLV packaging system containing D64V mutation in integrase. Using this special packaging system, Gentarget produces VSVG pseudotyped IDLV product lines, to satisfy the need for Non-integration lentivirus.

Gentarget’s IDLV products were verified with >95% integration reduction, via IDLV-GFP virus in 5-week cell expansion course. Gentarget IDLV maintains the most advanced, third-generation Bio-safety features, such as self-inactivation (SIN) and more. Our IDLVs are also replication-deficient lentivirus.

Why use Integration Defective Lentivirus (IDLV)?

1. Compared to other non-integrating virus delivery, like AAV or Adenovirus, IDLV has broad Cellular Tropism and the highest transduction rate. Most important, IDLV can deliver large targets (Gentarget’s proprietary IDLV system can effectively deliver up to 8kb gene-repair templates).
2. IDLV avoids the risks of Insertional Mutagenesis, yet still able to transduce both dividing and non-diving cells.
3. IDLV is best for transient over-expression, knockdown, CRISPR gene therapy in primary cells, or in “hard-to-delivery” cell types via other methods (like lipid transfection or electroporation). Dislike regular lentivirus, IDLV does not have the side-effect of unwanted footprint, like Cas9 stably expression.
4. As transient expression, IDLV effectively reduces the host’s immune rejection response to recombinant lentivector.

The features of Gentarget’s Integration Defective Lentivirus:

With more than 15 experience in lentivector development, Gentarget constructed the optimized lentivector system. The following scheme showed its IDLV core structure:

It provides two promoter selections (CMV or EF1a) to best fit your cell types, and the transient selection via different antibiotics or fluorescent signal.

Please see each IDLV product page below, or see the Product Manual.

References:

• Naldini, L., et al. (1996). Science 272: 263 – 267.
• Philippe, S., et al (2006) Proc. Natl. Acad. Sci. USA 103,17684–17689.;
• Nightingale et al (2006) Mol. Ther 13(6):1121-1132;
• Chamsy Sarkis et al (2008) Current Gene Therapy, 2008, 8, 430-437