Removal of transgene-expressing cells by a specific immune response induced by sustained transgene expression

Yin, Ye; Takahashi, Yuki; Ebisuura, Norifumi; Nishikawa, Makiya; Takakura, Yoshinobu

doi:10.1002/jgm.2763

Cited by 7 publications

(7 citation statements)

References 23 publications

(24 reference statements)

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“…These results indicate that the fall of Gluc levels in those mice cannot be explained by a decrease of Gluc expressing cells. We therefore hypothesize that the decrease of [Gluc] T0 could be due to the rise of a neutralizing antibody against Gluc, as suggested by Tannous 6 , but in contrast to what reported by other authors 19 . To test this possibility, we incubated a defined amount of Gluc with sera derived from mice having displayed low or irregular pattern of [Gluc] T0 over the time and found that 7 out of the 8 tested sera were able to dramatically inhibit Gluc activity (Figure 3 B-C).…”

Section: Resultscontrasting

confidence: 63%

Noninvasive Monitoring of Glioma Growth in the Mouse

et al. 2016

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Malignant gliomas are the most common and deadly primary malignant brain tumors. In vivo orthotopic models could doubtless represent an appropriate tool to test novel treatment for gliomas. However, methods commonly used to monitor the growth of glioma inside the mouse brain are time consuming and invasive. We tested the reliability of a minimally invasive procedure, based on a secreted luciferase (Gaussia luciferase), to frequently monitor the changes of glioma size.Gluc activity was evaluated from blood samples collected from the tail tip of mice twice a week, allowing to make a growth curve for the tumors. We validated the correlation between Gluc activity and tumor size by analysing the tumor after brain dissection. We found that this method is reliable for monitoring human glioma transplanted in immunodeficient mice, but it has strong limitation in immunocompetent models, where an immune response against the luciferase is developed during the first weeks after transplant.

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Section: Resultscontrasting

confidence: 63%

Noninvasive Monitoring of Glioma Growth in the Mouse

et al. 2016

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“…The CpG‐free plasmid lacks CpG sequences in the expression cassette and other parts, including the plasmid backbone, and was designed for long‐term gene expression. Some CpG‐containing transgenes and promoters achieved long‐term expression when the plasmid backbone lacked CpG sequences . Based on these findings, we suggested that the CpG‐free backbone could be the key component of the enhanced expression duration …”

Section: Introductionmentioning

confidence: 86%

Conventional plasmid DNAs with a CpG‐containing backbone achieve durable transgene expression in mouse liver

Suzuki

Wakao

Goda

et al. 2020

The Journal of Gene Medicine

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Background: Durable transgene expression from plasmid DNAs is the key to gene therapy with non-viral vectors. A comparison of the durability of transgene expression from plasmid DNAs with the CpG-free and -containing backbones is important. Methods:We constructed plasmid DNAs with the CpG-containing backbone, various transcription regulatory sequences with and without CpG, and the gene encoding Gaussia princeps luciferase, which is apparently non-immunogenic. The tail vein hydrodynamics-based method was used for plasmid injection into mice, and the luciferase activity in serum was tracked for 28 days. Results:The plasmid DNAs containing the albumin promoter [with or without the cytomegalovirus (CMV) enhancer] and the elongation factor (EF)1α promoter plus the CMV enhancer exhibited long-term luciferase expression. The expression from the plasmid DNA containing the albumin promoter without the CMV enhancer was maintained for at least 24 weeks and was similar to that from the corresponding CpG-free plasmid DNA. Conclusions:The results obtained in the present study suggest that special sequences/systems are unnecessary for durable transgene expression from plasmid DNAs when the proper transcription regulatory sequences are used. K E Y W O R D Shydrodynamics-based method, non-viral vector, plasmid DNA, transgene expression

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“…Any strategy aiming to introduce a stably expressed transgene in vivo will be beset with problems relating to immunogenicity. Several studies have shown efficient immune clearance of gene-engineered cells in the long term, even in severely immunocompromised patients ( 62 – 64 ). A potentially less immunogenic strategy might build on the finding that stabilized huTRIM5α is capable of HIV-1 restriction in vitro when expression is increased 20- to 30-fold ( 65 ).…”

Section: Potential Pitfalls and Strategies To Overcome Themmentioning

confidence: 99%

Targeting TRIM5α in HIV Cure Strategies for the CRISPR-Cas9 Era

2017

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In the past decade, studies of innate immune activity against HIV-1 and other retroviruses have revealed a powerful array of host factors that can attack the virus at various stages of its life cycle in human and primate cells, raising the prospect that these antiviral factors could be manipulated in immunotherapeutic strategies for HIV infection. This has not proved straightforward: while HIV accessory genes encode proteins that subvert or destroy many of these restriction factors, others, such as human TRIM5α show limited potency against HIV-1. However, HIV-1 is much more susceptible to simian versions of TRIM5α: could this information be translated into the development of an effective gene therapy for HIV infection? Reigniting research into the restriction factor TRIM5α in the era of superior gene editing technology such as CRISPR-Cas9 presents an exciting opportunity to revisit this prospect.

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Removal of transgene-expressing cells by a specific immune response induced by sustained transgene expression

Abstract: Our results demonstrate that sustained transgene expression in hepatocytes triggers antigen-specific immune responses, although short-term expression of the same transgene product elicits little, if any, immune response.

Cited by 7 publications

References 23 publications

Noninvasive Monitoring of Glioma Growth in the Mouse

Noninvasive Monitoring of Glioma Growth in the Mouse

Conventional plasmid DNAs with a CpG‐containing backbone achieve durable transgene expression in mouse liver

Targeting TRIM5α in HIV Cure Strategies for the CRISPR-Cas9 Era

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