Advancements in molecular design and bioprocessing of recombinant adeno‐associated virus gene delivery vectors using the insect‐cell baculovirus expression platform

Joshi, Pranav; Venereo-Sánchez, Alina; Chahal, Parminder S.; Kamen, Amine

doi:10.1002/biot.202000021

Cited by 36 publications

(25 citation statements)

References 103 publications

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“…Furthermore, the icosahedral capsid structure of AAV is known to be highly thermostable and thus possibly have reduced cold-chain requirements as a vaccine (Bennett et al, 2017;Pacouret et al, 2017;Rayaprolu et al, 2013). AAV production can be done at scale through a number of manufacturing methods that are well established in the industry to produce dozens of products currently in clinical development and available commercially (Joshi et al, 2020;Robert et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates

Zabaleta

Dai

Bhatt

et al. 2021

Cell Host & Microbe

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The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and are easily delivered. Here, AAVCOVID-1, an adeno-associated viral (AAV), Spike gene-based vaccine candidate demonstrates potent immunogenicity in mouse and nonhuman primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T-cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans, does not elicit cross-reactivity to common AAVs used in gene therapy, and its persistence and expression wanes following injection. The single, low dose requirement, high yield manufacturability, and 1-month stability for storage at room-temperature may make this technology well-suited to support effective immunization campaigns for emerging pathogens on a global scale.

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Section: Introductionmentioning

confidence: 99%

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates

Zabaleta

Dai

Bhatt

et al. 2021

Cell Host & Microbe

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show abstract

“…A representative BV system design that uses three vectors is displayed here, 63 but similar systems employing one or two vectors have also been developed. 74 The weak ΔIE-1 promoter lowers Rep78 expression level to achieve better yields and the ACG start codon for VP1 facilitates capsid protein production at a ratio closer to that found in AAVs made using mammalian cells (though the ratio is still not completely optimal). (B) Transduction of mammalian cells with engineered HSVs (carrying AAV components) is another alternative method which has been applied to AAV manufacturing.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Biology Design as a Paradigm Shift toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies

2023

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Gene therapy has demonstrated enormous potential for changing how we combat disease. By directly engineering the genetic composition of cells, it provides a broad range of options for improving human health. Adeno-associated viruses (AAVs) represent a leading gene therapy vector and are expected to address a wide range of conditions in the coming decade. Three AAV therapies have already been approved by the FDA to treat Leber’s congenital amaurosis, spinal muscular atrophy, and hemophilia B. Yet these therapies cost around $850,000, $2,100,000, and $3,500,000, respectively. Such prices limit the broad applicability of AAV gene therapy and make it inaccessible to most patients. Much of this problem arises from the high manufacturing costs of AAVs. At the same time, the field of synthetic biology has grown rapidly and has displayed a special aptitude for addressing biomanufacturing problems. Here, we discuss emerging efforts to apply synthetic biology design to decrease the price of AAV production, and we propose that such efforts could play a major role in making gene therapy much more widely accessible.

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“…The BEV platform has been used to express a wide range of proteins, including enzymes, glycoproteins, recombinant viruses, and vaccines [ 10 ]. The application of baculovirus as a vector for DNA delivery in humans is relatively safe because the virus cannot replicate in humans [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Application of Baculovirus Expression Vector system (BEV) for COVID-19 diagnostics and therapeutics: a review

Azali

Mohamed

Harun

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background The baculovirus expression vector system has been developed for expressing a wide range of proteins, including enzymes, glycoproteins, recombinant viruses, and vaccines. The availability of the SARS-CoV-2 genome sequence has enabled the synthesis of SARS-CoV2 proteins in a baculovirus-insect cell platform for various applications. Main body of the abstract The most cloned SARS-CoV-2 protein is the spike protein, which plays a critical role in SARS-CoV-2 infection. It is available in its whole length or as subunits like S1 or the receptor-binding domain (RBD). Non-structural proteins (Nsps), another recombinant SARS-CoV-2 protein generated by the baculovirus expression vector system (BEV), are used in the identification of new medications or the repurposing of existing therapies for the treatment of COVID-19. Non-SARS-CoV-2 proteins generated by BEV for SARS-CoV-2 diagnosis or treatment include moloney murine leukemia virus reverse transcriptase (MMLVRT), angiotensin converting enzyme 2 (ACE2), therapeutic proteins, and recombinant antibodies. The recombinant proteins were modified to boost the yield or to stabilize the protein. Conclusion This review covers the wide application of the recombinant protein produced using the baculovirus expression technology for COVID-19 research. A lot of improvements have been made to produce functional proteins with high yields. However, there is still room for improvement and there are parts of this field of research that have not been investigated yet.

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Advancements in molecular design and bioprocessing of recombinant adeno‐associated virus gene delivery vectors using the insect‐cell baculovirus expression platform

Cited by 36 publications

References 103 publications

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates

Synthetic Biology Design as a Paradigm Shift toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies

Application of Baculovirus Expression Vector system (BEV) for COVID-19 diagnostics and therapeutics: a review

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