Utilization of a novel Sendai virus vector in ex vivo gene therapy for hemophilia A

Yamaki, Yuni; Fukushima, Takashi; Yoshida, Naomi; Nishimura, Ken; Fukuda, Aya; Hisatake, Koji; Aso, Masayuki; Sakasai, Tomoki; Kijima-Tanaka, Junko; Miwa, Yoshiro; Nakanishi, Mahito; Sumazaki, Ryo; Takada, Hidetoshi

doi:10.1007/s12185-020-03059-6

Cited by 9 publications

(3 citation statements)

References 29 publications

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“…Beyond elucidating novel mechanisms of persistent infection, advancing viral vectors based on persistently infectious strains holds promise for future applications. SeVs have been explored as viral vectors for various applications, such as for the establishment of induced pluripotent stem cell lines and gene therapy (72)(73)(74). SeV vectors used for gene transfer are based on temperature-sensitive strains and can be removed from infected cells after gene transfer.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary engineering and characterization of Sendai virus mutants capable of persistent infection and autonomous production

Iwata,

Kawabata,

Morimoto

et al. 2024

Front. Virol.

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Persistent virus infection involves modifying the host immune response and maintaining viral infection. Acute infection with Mononegavirales, such as Sendai viruses (SeVs), can give rise to viruses capable of persistent infection. SeVs establish persistent infection through generating copyback-type defective interfering (cbDI) genomes or acquiring temperature-sensitive mutations. Herein, we identify novel mutations associated with persistent infection and recombinant SeV mutants capable of persistent infection and autonomous production at physiological body temperature, independent of cbDI genomes or temperature-sensitive mutations. Diverse SeV populations were generated by passing the cDNA-recovered SeV Z strain 19 times through embryonated chicken eggs and subsequently infecting LLC-MK2 cells with the SeV populations to finally obtain SeV mutants capable of persistent infection and autonomous production in several types of cultured cells. Sequence analysis identified 4 or 5 mutations in the genome of the persistently infectious SeVs, distinguishing them from other existing strains with persistent infection. Recombinant SeVs carrying 4 or 5 mutations in the Z strain genome (designated SeV-Zpi or SeV-Zpi2, respectively) exhibited persistent infection and autonomous production in LLC-MK2, BHK-21, and Neuro2a cells at 37°C. SeV-Zpi and SeV-Zpi2 consistently produced viral particles even after long-term passages without cbDI particles or temperature-sensitive phenotypes. These results highlight the ability of acute infections of SeVs to spontaneously acquire mutations during replication, thereby endowing persistent infection and autonomous production at body temperature. The vectorization of SeV-Zpi and SeV-Zpi2 will contribute to both basic research and medical applications.

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Section: Discussionmentioning

confidence: 99%

Evolutionary engineering and characterization of Sendai virus mutants capable of persistent infection and autonomous production

Iwata,

Kawabata,

Morimoto

et al. 2024

Front. Virol.

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“…A previous trial that delivered HIF-1α via adenovirus to treat limb ischemia demonstrated a negative effect, which was likely due to the weak transfection ability of adenovirus in skeletal muscle. In contrast, the SeV vector can overcome this limitation due to its capability of transducing non-dividing cells, including muscle cells (25,26). Vectors encoding angiogenic factors can be delivered to ischemic muscle tissues via intra-arterial or intramuscular routes for therapeutic angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic angiogenesis with intramuscular SeV-hFGF2/dF for the treatment of peripheral arterial disease: a phase I clinical trial

Lian¹,

Li²,

Rong³

et al. 2023

Preprint

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This paper reports a phase I dose-escalation clinical trial for the treatment of peripheral arterial disease (PAD) with BF30, a recombinant Sendai virus vector carrying the human native fibroblast growth factor 2 (hFGF2) gene. Our goal was to evaluate the safety and tolerability of BF30 at varying doses while assessing its preliminary therapeutic effect. Twelve male patients with PAD unsuitable for revascularization procedures that met the enrollment criteria were recruited. Each patient received a BF30 injection on one side of the ischemic lower limb. No deaths occurred prior to the 6-month follow-up. No severe adverse events or Grade 3/4 adverse events related to the BF30 injections were noted. Furthermore, the viral genome level was below the quantization limit after 6 months, and hemagglutination activity was undetectable in seven of the 12 cases. Abnormal changes in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and proinflammatory factor serum levels were not observed. None of the cases exhibited a positive anti-drug antibody signal. In addition, a positive therapeutic effect was demonstrated by the reduction in rest pain and Rutherford classification and improvement of the ankle-brachial index. While a higher dose triggered a stronger immune response, it was more effective in improving the Rutherford classification and quality of life.

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“…BHK‐21 (Baby hamster‐derived kidney cells) cells were obtained and used as described previously (Yamaki et al., 2021). These cells were maintained in DMEM supplemented with 10% FBS and 1% PSG at 37°C in a 5% CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

Production of therapeutic iduronate‐2‐sulfatase enzyme with a novel single‐stranded RNA virus vector

Ohira

Kikuchi

Mizuta³

et al. 2021

Genes to Cells

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The Sendai virus vector has received a lot of attention due to its broad tropism for mammalian cells. As a result of efforts for genetic studies based on a mutant virus, we can now express more than 10 genes of up to 13.5 kilo nucleotides in a single vector with high protein expression efficiency. To prove this benefit, we examined the efficacy of the novel ribonucleic acid (RNA) virus vector harboring the human iduronate‐2‐sulfatase (IDS) gene with 1,653 base pairs, a causative gene for mucopolysaccharidosis type II, also known as a disorder of lysosomal storage disorders. As expected, this novel RNA vector with the human IDS gene exhibited its marked expression as determined by the expression of enhanced green fluorescent protein and IDS enzyme activity. While these cells exhibited a normal growth rate, the BHK‐21 transformant cells stably expressing the human IDS gene persistently generated an active human IDS enzyme extracellularly. The human IDS protein produced failed to be incorporated into the lysosome when cells were pretreated with mannose‐6‐phosphate, demonstrating that this human IDS enzyme has potential for therapeutic use by cross‐correction. These results suggest that our novel RNA vector may be applicable for further clinical settings.

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Utilization of a novel Sendai virus vector in ex vivo gene therapy for hemophilia A

Cited by 9 publications

References 29 publications

Evolutionary engineering and characterization of Sendai virus mutants capable of persistent infection and autonomous production

Evolutionary engineering and characterization of Sendai virus mutants capable of persistent infection and autonomous production

Therapeutic angiogenesis with intramuscular SeV-hFGF2/dF for the treatment of peripheral arterial disease: a phase I clinical trial

Production of therapeutic iduronate‐2‐sulfatase enzyme with a novel single‐stranded RNA virus vector

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