Alphavirus vectors as tools in neuroscience and gene therapy

Lundström, Kenneth

doi:10.1016/j.virusres.2015.08.015

Cited by 9 publications

(4 citation statements)

References 84 publications

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“…During previous decades, the understanding of viral vectors has increased, concomitant with improvement in their design and production. Based on this progress, a number of viral vectors have been identified and explored for gene delivery, including commonly used viral vectors, such as adenovirus, adeno-associated virus (AAV), retrovirus, herpes simplex virus (HSV), lentivirus, and poxvirus ( 45 ), and certain novel developed viral vectors, such as alphavirus vectors ( 48 ). Among these, lentiviral vectors and AAV vectors have been the subject of focus in previous years ( 20 ), and a recent patent has provided novel methods to shield the lentiviral vectors with a thin polymer shell, conferring the shielded virus novel binding ability with additional characteristics, including higher thermal stability, resistance to serum inactivation and the ability to infect cells with high efficiency ( 49 ).…”

Section: Delivery Systems For Gene Therapymentioning

confidence: 99%

Tumor angiogenesis and anti‑angiogenic gene therapy for cancer (Review)

et al. 2018

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When Folkman first suggested a theory about the association between angiogenesis and tumor growth in 1971, the hypothesis of targeting angiogenesis to treat cancer was formed. Since then, various studies conducted across the world have additionally confirmed the theory of Folkman, and numerous efforts have been made to explore the possibilities of curing cancer by targeting angiogenesis. Among them, anti-angiogenic gene therapy has received attention due to its apparent advantages. Although specific problems remain prior to cancer being fully curable using anti-angiogenic gene therapy, several methods have been explored, and progress has been made in pre-clinical and clinical settings over previous decades. The present review aimed to provide up-to-date information concerning tumor angiogenesis and gene delivery systems in anti-angiogenic gene therapy, with a focus on recent developments in the study and application of the most commonly studied and newly identified anti-angiogenic candidates for anti-angiogenesis gene therapy, including interleukin-12, angiostatin, endostatin, tumstatin, anti-angiogenic metargidin peptide and endoglin silencing.

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Section: Delivery Systems For Gene Therapymentioning

confidence: 99%

Tumor angiogenesis and anti‑angiogenic gene therapy for cancer (Review)

et al. 2018

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“…Alphaviruses are a group of small, enveloped, medically relevant positive-sense RNA viruses with genomes of 11–12 kilobases in length ( Leung et al, 2011 ). Our rationale for using an alphavirus clone for these studies was their ease of use and that they have been used as expression vectors for foreign proteins extensively ( Singh et al, 2019 ; Lundstrom, 2016 ). Following transfection, we collected virus each day until 90% of the cells showed cytopathic effect (CPE), which occurred by day three in all cases.…”

Section: Resultsmentioning

confidence: 99%

Rolling circle amplification: A high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones

2020

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Alphaviruses (genus Alphavirus ; family Togaviridae ) are a medically relevant family of viruses that include chikungunya virus and Mayaro virus. Infectious cDNA clones of these viruses are necessary molecular tools to understand viral biology. Traditionally, rescuing virus from an infectious cDNA clone requires propagating plasmids in bacteria, which can result in mutations in the viral genome due to bacterial toxicity or recombination and requires specialized equipment and knowledge to propagate the bacteria. Here, we present an alternative-rolling circle amplification (RCA), an in vitro technology. We demonstrate that the viral yield of transfected RCA product is comparable to midiprepped plasmid, albeit with a slight delay in kinetics. RCA, however, is cheaper and less time-consuming. Further, sequential RCA did not introduce mutations into the viral genome, subverting the need for glycerol stocks and retransformation. These results indicate that RCA is a viable alternative to traditional plasmid-based approaches to viral rescue.

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“…Self-replicating alphavirus vectors can generally be delivered as recombinant virus particles, RNA replicons, or layered DNA/RNA plasmid vectors. 7 The recombinant virus particles are mostly called virus-like particles (VRPs). They are also known as virus-like replicon particles (VLPs).…”

Section: Discussionmentioning

confidence: 99%

A novel three‐plasmid packaging system for chimeric SFV/SIN VRPs derived from Semliki Forest virus and Sindbis virus as a candidate gene delivery vector

Huang,

Dong,

Liu

et al. 2024

Journal of Medical Virology

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Semliki Forest virus (SFV) viral replicon particles (VRPs) have been frequently used in various animal models and clinical trials. Chimeric replicon particles offer different advantages because of their unique biological properties. We here constructed a novel three‐plasmid packaging system for chimeric SFV/SIN VRPs. The capsid and envelope of SIN structural proteins were generated using two‐helper plasmids separately, and the SFV replicon contained the SFV replicase gene, packaging signal of SIN, subgenomic promoter followed by the exogenous gene, and 3′ UTR of SIN. The chimeric VRPs carried luciferase or eGFP as reporter genes. The fluorescence and electron microscopy results revealed that chimeric VRPs were successfully packaged. The yield of the purified chimeric VRPs was approximately 2.5 times that of the SFV VRPs (1.38 × 107 TU/ml vs. 5.41 × 106 TU/ml) (p < 0.01). Furthermore, chimeric VRPs could be stored stably at 4°C for at least 60 days. Animal experiments revealed that mice immunized with chimeric VRPs (luciferase) had stronger luciferase expression than those immunized with equivalent amount of SFV VRPs (luciferase) (p < 0.01), and successfully expressed luciferase for approximately 12 days. Additionally, the chimeric VRPs expressed the RBD of SARS‐CoV‐2 efficiently and induced robust RBD‐specific antibody responses in mice. In conclusion, the chimeric VRPs constructed here met the requirements of a gene delivery tool for vaccine development and cancer therapy.

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Alphavirus vectors as tools in neuroscience and gene therapy

Cited by 9 publications

References 84 publications

Tumor angiogenesis and anti‑angiogenic gene therapy for cancer (Review)

Tumor angiogenesis and anti‑angiogenic gene therapy for cancer (Review)

Rolling circle amplification: A high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones

A novel three‐plasmid packaging system for chimeric SFV/SIN VRPs derived from Semliki Forest virus and Sindbis virus as a candidate gene delivery vector

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