sLTR

Solitary LTR vectors (sLTR) are a new family of recombinant retroviral vectors (RRV). They allow the modification of mammalian genome by inserting a DNA sequence and control the deletion of unnecessary viral sequences. sLTRs use retroviruses to insert into cells with safety and control.

The sLTR process relies on two elements, on one hand the ability of retroviruses to duplicate sequences during replication and on the other hand on a recombinase system. These two elements allow a controlled induction of deletion of viral sequences of the host genome.
sLTR vectors have two integrated structural stages in cells. The first stage is the full integration of the provirus and the second stage is the self deletion resulting in the sLTR (watch the animation).
Therefore, all cis viral regulatory elements of the provirus, including the ones necessary for the control of transcription, reverse transcription, encapsidation and integration, are absent from the transduced material.
sLTRs allow the introduction in genomic DNA of cells: of a foreign gene, either for a very limited controlled period of time, or a gene of interest, integrated into the genome deleted of most proviral sequences.

Compared to classical RRVs, sLTRs allow safety and control in cell transgenesis. Because of their inability to retrotranspose or generate Replication Competent Retroviruses (RCRs), the sLTR family of recombinant retroviruses overcomes problems associated with the presence of viral sequences that negatively control the expression of the transduced material in cells and more particularly in stem cells. These sequences, like the primer binding site (PBS) or the two LTRs, can lead to the silencing of the transduced gene and result in the use of higher multiplicity of infection (MOI).

Self deletion can lead either to full deletion of transduced genes (showed in the anumation) or to deletion of most proviral sequences in order to secure transgene expression and generation of RCRs.

Why is the use of sLTRs?

Self-deleting vectors can have numbers of applications including:

• Gene therapy
• Gene trapping (promoter or enhancer trap)
• Gene activation
• Conditional transduction
• Gene delivery