The Magic Staff: A Comprehensive Overview of Baculovirus-Based Technologies Applied to Human and Animal Health

Abstract

Baculoviruses are enveloped, insect-specific viruses with large double-stranded DNA genomes. Among all the baculovirus species, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the most studied. Due to its characteristics regarding biosafety, narrow host range and the availability of different platforms for modifying its genome, AcMNPV has become a powerful biotechnological tool. In this review, we will address the most widespread technological applications of baculoviruses. We will begin by summarizing their natural cycle both in larvae and in cell culture and how it can be exploited. Secondly, we will explore the different baculovirus-based protein expression systems (BEVS) and their multiple applications in the pharmaceutical and biotechnological industry. We will focus particularly on the production of vaccines, many of which are either currently commercialized or in advanced stages of development (e.g., Novavax, COVID-19 vaccine). In addition, recombinant baculoviruses can be used as efficient gene transduction and protein expression vectors in vertebrate cells (e.g., BacMam). Finally, we will extensively describe various gene therapy strategies based on baculoviruses applied to the treatment of different diseases. The main objective of this work is to provide an extensive up-to-date summary of the different biotechnological applications of baculoviruses, emphasizing the genetic modification strategies used in each field.

Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer

“…In addition, due to the well-known capacity of BVs to incorporate large foreign genetic information, other BV-enhancing genes may be incorporated in addition to the therapeutic gene. In this way, BVs with increased transduction efficiency [ 53 , 54 , 55 , 56 , 57 ] and with the ability to display specific tumor receptor ligands on the surface of the virion have been developed [ 20 , 58 ]. These technologies could be exploited to improve the transgene expression and specificity of BVs for the treatment of brain disorders.…”

“…These vectors do not integrate in the host genome and are non-replicative in mammalian cells. A great advantage of BVs is their great capacity to accommodate foreign DNA, as they have a circular genome of 134 kb with an insertion capacity that easily exceeds 38 kb and can accommodate multiple gene sequences required for the assembly of large protein complexes using recombinant virus construction systems such as MultiBac and HR-Bac [ 17 , 18 , 19 , 20 ]. Its most salient characteristic is that no pre-existing immunity against BV has been detected in humans, and thus, BV transduction would be more stable than AdV, especially in immunologically privileged tissues such as the brain.…”

Mitochondrial Peptide Humanin Facilitates Chemoresistance in Glioblastoma Cells

“…In this sense, baculoviruses (BVs) represent useful tools to be used as gene therapy vectors. These vectors are relatively simple to produce and purify at high titers and have a broad cloning capacity, allowing the transfer of multiple transgenes and regulatory elements simultaneously [ 47 , 48 ]. Furthermore, since they are natural insect pathogens, patients do not possess pre-existing immunity against these vectors [ 47 ].…”

Helical reconstruction of VP39 reveals principles for baculovirus nucleocapsid assembly

“…The biosafety properties and high target specificity of baculoviruses have led to their development as biological control agents, with growing importance due to the increase in insecticide resistance, compounded by climate disruption 1,2 . Baculoviruses are also wellestablished biotechnological platforms for heterologous protein expression [3][4][5][6][7] , vaccine production 8 , and therapeutic gene delivery 9 . Despite decades of study, the structural basis for baculovirus assembly has remained unknown.…”