cells [4]. Therefore, effective transfer vectors need to fulfill the
following criteria [5]:
1. Immune reactions to the nucleic acids must be prevented by
the vector.
2. The cargo (in this case the nucleic acid) must be delivered to
specific cells.
3. The vector should infect dividing and nondividing cells.
4. The vector must allow the unimpeded expression of the
(recombinant) gene.
5. The transport of nucleic acids with varying sizes must be
feasible.
6. The vector production must be economically profitable: simple, cost-effective, and in high concentrations.
Viral vectors were the first vectors to be used and still represent
the major share of today’s medicinal applications for gene therapy
[2]. The most common candidates are the adenovirus [6], the
adeno-associated virus [7], the gammaretrovirus [8], and lentivirus
vectors [9]. Comprehensive descriptions of their assets and drawbacks can be found elsewhere [4, 10]. Here, the focus lies on the
infrequently used, but very promising baculovirus vector (BV).
Natural baculoviruses infect insect cells and are enveloped dsDNA
viruses with rod-shaped nucleocapsids with a size of
30–60 nm  250–300 nm and a circular DNA.
Different applications of baculoviruses have been used for decades. Since the discovery of the baculovirus Autographa californica
multicapsid nucleopolyhedrovirus (AcMNPV) (134 kb [11]) in
1971 [12], its use as a sustainable and safe pesticide was investigated. Next, the baculovirus expression vector system (BEVS) was
developed for the production of recombinant proteins in the 1980s
[13]. It is still extensively used for the production of vaccine candidates [14–16]. Furthermore, the BEVS was approved by EMA
(European Medicines Agency) and FDA (Food and Drug Administration). Finally, the ability of the baculovirus to transduce eukaryotic cells was discovered in the mid-1990s [17], which opened the
doors for gene therapy applications. The transduction of various
types of cells and tissue is possible today [18–22].
In comparison to the prior mentioned viral vectors, the BV
shows several advantages. First, the baculoviral genome allows a
stable insertion of complex gene cassettes up to a length of 47 kb
[23]. Secondly, it is nonpathogenic for humans and can be handled
in biosafety level I laboratories. The baculovirus is inherently incapable of replicating in mammalian cells [24], that is, the DNA
degrades inside the transduced cells [25] while its integration into
the host genome is almost never found [26]. Thirdly, the baculovirus is not targeted by the human immune system as no specific
368
Friederike Eilts et al.
following criteria [5]:
1. Immune reactions to the nucleic acids must be prevented by
the vector.
2. The cargo (in this case the nucleic acid) must be delivered to
specific cells.
3. The vector should infect dividing and nondividing cells.
4. The vector must allow the unimpeded expression of the
(recombinant) gene.
5. The transport of nucleic acids with varying sizes must be
feasible.
6. The vector production must be economically profitable: simple, cost-effective, and in high concentrations.
Viral vectors were the first vectors to be used and still represent
the major share of today’s medicinal applications for gene therapy
[2]. The most common candidates are the adenovirus [6], the
adeno-associated virus [7], the gammaretrovirus [8], and lentivirus
vectors [9]. Comprehensive descriptions of their assets and drawbacks can be found elsewhere [4, 10]. Here, the focus lies on the
infrequently used, but very promising baculovirus vector (BV).
Natural baculoviruses infect insect cells and are enveloped dsDNA
viruses with rod-shaped nucleocapsids with a size of
30–60 nm  250–300 nm and a circular DNA.
Different applications of baculoviruses have been used for decades. Since the discovery of the baculovirus Autographa californica
multicapsid nucleopolyhedrovirus (AcMNPV) (134 kb [11]) in
1971 [12], its use as a sustainable and safe pesticide was investigated. Next, the baculovirus expression vector system (BEVS) was
developed for the production of recombinant proteins in the 1980s
[13]. It is still extensively used for the production of vaccine candidates [14–16]. Furthermore, the BEVS was approved by EMA
(European Medicines Agency) and FDA (Food and Drug Administration). Finally, the ability of the baculovirus to transduce eukaryotic cells was discovered in the mid-1990s [17], which opened the
doors for gene therapy applications. The transduction of various
types of cells and tissue is possible today [18–22].
In comparison to the prior mentioned viral vectors, the BV
shows several advantages. First, the baculoviral genome allows a
stable insertion of complex gene cassettes up to a length of 47 kb
[23]. Secondly, it is nonpathogenic for humans and can be handled
in biosafety level I laboratories. The baculovirus is inherently incapable of replicating in mammalian cells [24], that is, the DNA
degrades inside the transduced cells [25] while its integration into
the host genome is almost never found [26]. Thirdly, the baculovirus is not targeted by the human immune system as no specific
368
Friederike Eilts et al.