Expression of Foreign Genes in Bombyx mori Larvae Using Baculovirus Vectors

Baculovirus expression vector systems based on the nuclear polyhedrosis viruses of
Autographa californica
(AcNPV) and
Bombyx mori
(BmNPV) are in wide use (
1
). Our laboratory originally designed the BmNPV system with the objective of using the silkworm,
B. mori
, as an in vivo host (
1a
,
2
). The silkworm belongs to the order, Lepidoptera (butterflies and moths), consisting of herbivorous insect species that feed on foliage plants in the wild. Because of its economic importance in silk production, the silkworm has been domesticated for thousands of years. The larvae have traditionally been cultivated on leaves of the mulberry bush
(Morus alba)
. Furthermore, in recent years, the silkworm has become an ideal multicellular eukaryotic model system for basic research. Although both the AcNPV and BmNPV systems provide highlevel expression of foreign genes using larval hosts (
3
,
4
), the silkworm larva offers several additional advantages, i.e., it is easy to rear, it is large and easy to manipulate, it has a relatively short life cycle (approx 7 wk), and its genetics and biology have been well documented. The availability of automated rearing equipment and the fact that the larvae are nonallergenic to human handlers make scale-up and mass production of recombinant proteins under sterile conditions very attractive.