The enabling technology called the Baculovirus Expression Vector System
(BEVS) for the safe, abundant and rapid production of recombinant proteins
in insect cells and insects was pioneered in the laboratory of Dr. Max
D. Summers (US Patent No. 4,745,051: Method for Producing a Recombinant
baculovirus Expression Vector. (Smith/Summers) (Granted May 17, 1988).
This system was developed from basic studies of insect pathogenic
viruses for pest control of medically and agriculturally important insects.
More specifically, the technology was the result of the identification,
cloning and genetic engineering of a baculovirus gene which expresses
very abundant quantities of a viral-encoded protein in infected insect
cells. The virus, insect cells and insects are all sources for expression
and recombinant protein production which do not represent potential harm
or threat to man, plants or animals. The BEVS is a discovery with
very broad enabling applications and impact spanning the basic life sciences
and biotechnology. The BEVS has become a core technology for: 1)
the cloning and expression of genes for study of protein structure, processing
and function; 2) the production of biochemical reagents; 3) the study
of regulation of gene expression; 4) the commercial exploration, development
and production of vaccines, therapeutics and diagnostics; 5) drug discovery
research; 6) the exploration and development of safer, more selective
and environmentally compatible biopesticides consistent with sustainable
agriculture. As stated in a recent meeting review, “ The immediate
challenge created by the genomics era is the production of the novel proteins
to understand their function. Due to its advantages in versatility
and speed, the Baculovirus expression system of choice in the future given
the large number of products already in clinical development and the recent
achievements in increasing the expression levels in this system”
In addition, the scientific and biotechnology literature records many
significant original advances in biology, molecular biology and biochemistry
from the use of the BEVS resulting from the cloning, production and study
of more than 1000 eukaryotic, prokaryotic and viral recombinant proteins
(search http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed, using
keywords, BEVS or Baculovirus). And, the BEVS and its applications
for discovery, development and commercial production areas of medicine
and agriculture are responsible for the commercial development of many
new biotechnology initiatives and activities in established and start-up
industries worldwide- USA, Europe, Japan, Australia.
Studies of proteins for
the development of drug therapies, vaccines, and insights into biological
function depend upon the ability to produce large amounts of structurally
complex proteins. It is important that these proteins are biologically
active, processed correctly, assume a native shape, and locate to the
proper place in the cell. The inability to generate large quantities
of structurally complex eukaryotic proteins with these characteristics
was a major stumbling block for many years. Who would have thought that
these problems would be largely overcome by insights derived from studies
of a virus that infects insects? And the use of such insights to
develop the Baculovirus Expression Vector System (BEVS). This system
is capable of generating large quantities of biologically active recombinant
protein inexpensively and quickly. To date, over a thousand proteins
have been expressed using the BEVS, with 98% being biologically active.
The BEVS represents a core technology that has greatly facilitated the
understanding of many proteins from species that span the life sciences.
These studies have broad applications and impact in basic research
and practical medical applications for both humans and animals.
One example of the application and efficiency of the BEVs was the rapid
development of an experimental vaccine to the deadly Hong Kong “bird-flu”
virus (HSN1). Another was the rapid development of SARS vaccine.
NIH requested the development of a vaccine and Protein Sciences (a company
that specializes in BEVS technology) delivered 1700 doses of an experimental
“bird-flu” vaccine within eight weeks. This included
the time to identify, sequence and clone the gene responsible for the
flu symptoms. The efficiency, low cost and large-scale production
of proteins using BEVS represents breakthrough technology that is facilitating
high-throughput proteomic studies. The BEVS is being used widely
in drug discovery and the development of protein crystals of medically
important proteins. With the knowledge of the 3-dimensional structure,
precise design of drugs that will act as ‘magic bullets’ for
the intervention of many diseases states is currently underway both in
the private sector and academia.
The important and broad
acceptance of the BEVS technology is reflected in its acceptance in both
the academic community and private sector. The broad recognition and acceptance
by the scientific community is reflected in the determination by The Institute
of Scientific Information (ISI) that Dr. Summers is one of the top 250
most highly cited microbiologists in the world. Acceptance of the BEVS
by the private sector is reflected by the commercial licenses worldwide
that are held for the BEVS technology (currently >70). Thousands
of laboratories currently use the BEVS technology in their research programs.
