Development and Applications of Non-HIV-Based Lentiviral Vectors in Neurological Disorders

Chiara   F.   Valori; Ke      Ning; Matthew      Wyles; Mimoun      Azzouz

Abstract

Vectors based on non-HIV lentiviruses are opening up new approaches for the treatment of human disorders. These vectors efficiently deliver genes into many different types of cells from a broad range of species including man and the resulting gene expression is long-term. These features make them very attractive to be transformed into tools for gene therapy. HIV-1 based lentiviral vectors were initially developed, a process which provided valuable insights into the biology of these vectors allowing progressive improvement of non-HIV vectors. The latest vectors have been refined to a very high level and can be produced safely for the clinic. This review will describe the general features of lentiviral vectors with particular emphasis on vectors derived from the non-HIV lentiviruses such as equine infectious anaemia virus (EIAV), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV). It will then describe some key examples of gene therapy applications in neurological diseases such as Parkinsons disease (PD), motor neuron diseases, lysosomal storage diseases and ocular disorders. Finally, the prospects for clinical application of non-HIV lentiviral vectors for these disorders will also be outlined.

Keywords: SIV, FIV, EIAV, packaging cell line, pseudotyping, vector tropism