Yes. This article describes gene knockdown with siRNA using a lentiviral vector both in vitro and in vivo.
This study was designed as a "proof of concept" and was published in 2003. I only cited it to answer your initial question. I'm not active in research anymore so I can't advise you of the current status of this approach. You might try to contact the authors.Thanks.
Is there any leakage from unbinded mRNA fragments that then do get translated into proteins?
Could one tailor a virus to splice the siRNA DNA into a target cell so the siRNA could be manufactured inter-cellularly? (I.E. Lytic cycle without the virus parts)
Gene therapy has been pursued for more than a decade, with not much success:siRNA, from my understanding, can interfere with gene expression post-transcriptionally and therefore can be used on an unprimed (if you will) genome. I feel this route has more promise for clinical applications. A few questions.
****. The immune response didn't even cross my mindGene therapy has been pursued for more than a decade, with not much success:
I'm (somewhat) familiar with the case of Jesse Gelsinger. He had a variant of cystic fibrosis, which was identified as a candidate disease for gene therapy since the lung is an easy organ to target (inhale the carrier).
People are still trying various approaches with some success, but progress is very slow.
Yes, you can still have low level protein expression even thought the mRNA from is being silenced by RNA interference. In fact, biologists make a distinction between "knocking out" a gene (removing or disrupting a gene such that the cell is incapable of producing the mRNA for the target protein) and "knocking down" a gene (using RNA interference to silence a gene). Incomplete knock-down of a gene is a potential problems faced by those using RNA interference. However, if this is the case, one can still design better siRNAs or combine multiple siRNAs to achieve a better knock down of the target protein.Is there any leakage from unbinded mRNA fragments that then do get translated into proteins?
Yes, people engineer lentiviruses (the same family of viruses as HIV) to integrate sequences that express the appropriate siRNA into cells. This technique works well for cultured cells, but as Andy said, there are problems with using this method in living humans.Could one tailor a virus to splice the siRNA DNA into a target cell so the siRNA could be manufactured inter-cellularly? (I.E. Lytic cycle without the virus parts)