Virus production for clinical gene therapy.
Gene therapy is becoming increasingly relevant for the treatment of prominent human diseases. Viral vectors are currently used in more than 50% of the gene therapy clinical trials, most of them aimed at cancer diseases. Clearly, the increasing needs of high-quality viral preparations require the elimination of process bottlenecks, streamlining the development of a viral vector into a real-world clinical tool. Virus production for clinical gene therapy can be a limiting step because many virus generation protocols rely on labor-intensive, bench-scale methods; robust, cost-effective strategies for the delivery of clinical-grade viruses are thus essential for the future of gene therapy. A comprehensive picture of key aspects on the integration of upstream and downstream processing is addressed in this chapter, by describing the case study of recombinant budded baculoviruses for gene therapy; scalable methods are described in detail as well as mandatory characterization techniques for a proper and complete quality assessment of the viral vectors.
Vicente
Tiago
T
Instituto de Biologia Experimental e Tenológica (IBET), Oeiras, Portugal.
Peixoto
Cristina
C
Carrondo
Manuel J T
MJ
Alves
Paula M
PM
D000818:Animals; D016367:Baculoviridae; D019149:Bioreactors; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D015151:Immunoblotting; D014462:Ultrafiltration; D014764:Viral Proteins / Q000378:metabolism; D014780:Viruses / Q000378:metabolism*
D014764:Viral Proteins