Production and formulation of adenovirus vectors.
Adenovirus vectors have attracted considerable interest over the past decade, with ongoing clinical development programs for applications ranging from replacement therapy for protein deficiencies to cancer therapeutics to prophylactic vaccines. Consequently, considerable product, process, analytical, and formulation development has been undertaken to support these programs. For example, "gutless" vectors have been developed in order to improve gene transfer capacity and durability of expression; new cell lines have been developed to minimize recombination events; production conditions have been optimized to improve volumetric productivities; analytical techniques and scaleable purification processes have advanced towards the goal of purified adenovirus becoming a "well-characterized biological"; and liquid formulations have been developed which maintain virus infectivity at 2-8 degrees C for over 18 months. These and other advances in the production of adenovirus vectors are discussed in detail in this review. In addition, the needs for the next decade are highlighted.
Altaras
Nedim E
NE
Fermentation and Cell Culture, Merck Research Laboratories, West Point, Pennsylvannia 19486-0004, USA.
Aunins
John G
JG
Evans
Robert K
RK
Kamen
Amine
A
Konz
John O
JO
Wolf
Jayanthi J
JJ
D000256:Adenoviridae / Q000235:genetics*; D005822:Genetic Vectors