Progress to Date
Demonstrating the Efficiency of the Sendai Virus Vector
Pseudotyping a SIV Vector with the SeV H&FN Proteins
Gene Transfer Efficiency from SeV Pseudotyped SIV
What remains to be done to get SIV to the clinic?
Demonstrating the Efficiency of the Sendai Virus Vector^Top
The Consortium has been working with DNAVEC for some years on various aspects of this work. Initially we demonstrated the efficiency the Sendai Virus (SeV) vector in the respiratory epithelium (Griesenbach et al 2002 , Ferrari et al 2004 & Griesenbach et al 2010).
However, while incredibly efficient the duration of expression from SeV was very poor as the vector system is entirely RNA based and persists in the cells for only a few days.
The efficiency of SeV was largely due to the function of its coat proteins.
Pseudotyping a SIV Vector with the SeV H&FN Proteins^Top
The early promise of the SeV led DNAVEC to clone the SeV H&FN proteins and create a novel Simian immunodeficiency virus vector with the H&FN proteins in order to re-target it to respiratory epithelia (Kobayashi et al 2003).
Gene Transfer Efficiency from SeV Pseudotyped SIV^Top
Over the past few years the consortium has been assessing the gene transfer efficiency of the pseudotyped SIV in a number of models (Mitomo et al 2010).
We have demonstrated that the vector has long lived expression in the murine airways with high levels of reporter gene activity observed for at least two years post administration (right).
More significantly, we have demonstrated that the vector can be re-administered twice to mice without any loss of activity relative to the first dose. This is major advance because no other viral vector has been shown to be repeatable in this manner, not with the associated high levels of expression (left).
What remains to be done to get this to the clinic?^Top
Despite thie progress, many years of work will likely be required if this vector is to be used in the clinic for CF. Much optimisation of the vector production process is required to increase the yield of vector produced and to provide an efficient expression cassette.
Most of this current work is highly publication sensitive so sadly it cannot be discussed here yet.
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