AAV-8 is Most Effective Viral Vector in Gene Therapy in CLL

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[2985] Comparison of Viral Vectors for Gene Transfer into CLL Cells:

Efficient Transduction with Adeno-Associated Virus-8 (AAV-8).

Session Type: Poster Session 236-III

P. Jewell, Cochrane, McIntosh, Reuben ,

Amit Nathwani Haematology, University College London Medical School,

London, United Kingdom; Faculty of Health and Social Care Sciences,

St 's University of London, London, United Kingdom

Chronic Lymphocytic Leukaemia (CLL) remains largely incurable

despite recent advances in therapy, and therefore alternative

strategies are of interest in treating this disease. One such

alternative is the use of gene therapy, but this relies on

developing efficient gene transfer technologies.

We have compared several viral vectors coding for green fluorescent

protein (GFP) for their ability to transduce CLL cells. Three

serotypes of adeno-associated virus (AAV) were used, AAV-2, AAV-5

and a relatively new isolate AAV-8, an EI-EIII deleted adenoviral 5

based vector, AV-5, all with GFP regulated by the CMV promoter, and

a VSVG pseudotyped lentiviral vector in which GFP expression is

controlled by EF1a promotor/enhancer complex. AV-5 resulted in

variable GFP expression, 24.1+3.4%, n=10 but caused cell death at

high multiplicities of infection (MOI).

The lentiviral vector resulted in GFP expression of 23.5+2.6%, n=12,

at the highest titre used, and expression declined in a distinct

dose-dependent manner as titres were reduced. Of the AAV vectors,

AAV-8 was the most efficient with GFP expression at 41.3+1.0% n=14.

We conclude that AAV-8 is a promising viral vector for efficient

transduction of CLL cells.