Manufacturing of AcMNPV baculovirus vectors to enable gene therapy trials

Abstract

Over the past two decades, baculoviruses have become workhorse research tools for transient transgene expression. Although they have not yet been used directly as a gene therapy vector in the clinical setting, numerous preclinical studies have suggested the highly promising potential of baculovirus as a delivery vector for a variety of therapeutic applications including vaccination, tissue engineering, and cancer treatment. As such, there is growing interest in using baculoviruses as human gene therapy vectors, which has led to advances in baculovirus bioprocessing methods. This review provides an overview of the current approaches for scaled-up amplification, concentration, purification, and formulation of AcMNPV baculoviruses, and highlights the key regulatory requirements that must be met before gene therapy clinical trials can be initiated.

Targeted Inhibition of the miR‐199a/214 Cluster by CRISPR Interference Augments the Tumor Tropism of Human Induced Pluripotent Stem Cell‐Derived Neural Stem Cells under Hypoxic Condition

“…The baculovirus is a kind of insect virus but able to transduce human cells efficiently. Unlike traditionally used human viral vectors, such as retrovirus, adenovirus, and adeno-associated virus, baculovirus is inherently incapable of replicating in human cells and there is no detectable preexisting immunity to baculovirus in human; hence, it has been extensively exploited as a novel gene delivery vector for clinical applications [36, 37]. Notably, another feature of the baculoviral vector is the large cargo capacity, up to 28 kb.…”

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“…In fact, both High Five and Sf9 cell lines have regulatory acceptance for manufacturing of biologicals, such as Cervarix, the GSK HPV vaccine, or Flublock, the Protein Sciences influenza vaccine. 33 …”

On Mr. Hyslop’s prediction, content archives, and preprint servers

“…Cheap and easy to engineer, the baculovirus expression system has proved to be vastly superior to alternative systems based on mammalian cells, handling individual or multiple proteins of almost any size and expressing them at high levels, properly folded, for the duration of the infection. AcMNPV remains the major virus species, along with its polyhedrin promoter, in use today as the expression vector in baculovirus expression vector systems for recombinant protein expression in a variety of contexts, including mass production of egg-free influenza vaccines such as FluBlok (7).…”