OneBac: platform for scalable and high-titer production of adeno-associated virus serotype 1-12 vectors for gene therapy

Hum Gene Ther. 2014 Mar;25(3):212-22. doi: 10.1089/hum.2013.184. Epub 2014 Jan 23.

Abstract

Scalable and genetically stable recombinant adeno-associated virus (rAAV) production systems combined with facile adaptability for an extended repertoire of AAV serotypes are required to keep pace with the rapidly increasing clinical demand. For scalable high-titer production of the full range of rAAV serotypes 1-12, we developed OneBac, consisting of stable insect Sf9 cell lines harboring silent copies of AAV1-12 rep and cap genes induced upon infection with a single baculovirus that also carries the rAAV genome. rAAV burst sizes reach up to 5 × 10(5) benzonase-resistant, highly infectious genomic particles per cell, exceeding typical yields of current rAAV production systems. In contrast to recombinant rep/cap baculovirus strains currently employed for large-scale rAAV production, the Sf9rep/cap cell lines are genetically stable, leading to undiminished rAAV burst sizes over serial passages. Thus, OneBac combines full AAV serotype options with the capacity for stable scale-up production, the current bottleneck for the transition of AAV from gene therapy trials to routine clinical treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics*
  • Baculoviridae / metabolism
  • Cell Line
  • Dependovirus / classification
  • Dependovirus / genetics*
  • Dependovirus / metabolism
  • Gene Expression Regulation, Viral
  • Genetic Vectors / genetics*
  • Genetic Vectors / isolation & purification*
  • HEK293 Cells
  • HeLa Cells
  • Helper Viruses
  • Humans
  • Transduction, Genetic
  • Transfection
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Viral Proteins