Lentivirus Mediated Pancreatic Beta-Cell-Specific Insulin Gene Therapy for STZ-Induced Diabetes

Erendor, Fulya; Eksi, Yunus Emre; Şahin, Elif; Balcı, Mustafa Kemal; Griffith, Thomas S.; Şanlıoğlu, Salih

doi:10.1016/j.ymthe.2020.10.025

Cited by 14 publications

(9 citation statements)

References 64 publications

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“…Such single gene disorders, which cannot be treated with current treatment methods, can be effectively treated with gene therapy. Here, lentivirus-mediated insulin gene therapy may be a permanent solution for MODY10 treatment as shown previously for T1D[ 72 , 100 ].…”

Section: Contribution Of Programmable Nucleases In the Creation Of Disease Models For Diabetesmentioning

confidence: 94%

Genome engineering and disease modeling via programmable nucleases for insulin gene therapy; promises of CRISPR/Cas9 technology

Eksi¹,

Şanlioğlu²,

Akkaya³

et al. 2021

WJSC

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Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change, insert, or remove a genomic sequence of interest. These advanced molecular tools include meganucleases, zinc finger nucleases, transcription activator-like effector nucleases and RNA-guided engineered nucleases (RGENs), which create double-strand breaks at specific target sites in the genome, and repair DNA either by homologous recombination in the presence of donor DNA or via the error-prone non-homologous end-joining mechanism. A recently discovered group of RGENs known as CRISPR/Cas9 gene-editing systems allowed precise genome manipulation revealing a causal association between disease genotype and phenotype, without the need for the reengineering of the specific enzyme when targeting different sequences. CRISPR/Cas9 has been successfully employed as an ex vivo gene-editing tool in embryonic stem cells and patient-derived stem cells to understand pancreatic beta-cell development and function. RNA-guided nucleases also open the way for the generation of novel animal models for diabetes and allow testing the efficiency of various therapeutic approaches in diabetes, as summarized and exemplified in this manuscript.

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Section: Contribution Of Programmable Nucleases In the Creation Of Disease Models For Diabetesmentioning

confidence: 94%

Genome engineering and disease modeling via programmable nucleases for insulin gene therapy; promises of CRISPR/Cas9 technology

Eksi¹,

Şanlioğlu²,

Akkaya³

et al. 2021

WJSC

Self Cite

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“…128 Consequently, VSV-G pseudotyped third-generation SIN lentiviral vectors became the preferred vector of choice to achieve long-term gene expression in vivo. 129,130 Integration-deficient lentiviral vectors were developed to rule out the risk of insertional mutagenesis completely. 131 These integrase-deficient lentiviral vectors have mutations in the catalytic domain of the viral integrase, preventing the integration of vector cDNA into the host genome.…”

Section: Lentivirus Structure and Vector Designmentioning

confidence: 99%

Current Update on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development with a Special Emphasis on Gene Therapy Viral Vector Design and Construction for Vaccination

et al. 2021

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Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease (COVID-19) caused by the novel coronavirus SARS-coronavirus 2 (CoV-2). To combat the devastating spread of SARS-CoV-2, extraordinary efforts from numerous laboratories have focused on the development of effective and safe vaccines. Traditional live-attenuated or inactivated viral vaccines are not recommended for immunocompromised patients as the attenuated virus can still cause disease via phenotypic or genotypic reversion. Subunit vaccines require repeated dosing and adjuvant use to be effective, and DNA vaccines exhibit lower immune responses. mRNA vaccines can be highly unstable under physiological conditions. On the contrary, naturally antigenic viral vectors with well-characterized structure and safety profile serve as among the most effective gene carriers to provoke immune response via heterologous gene transfer. Viral vector-based vaccines induce both an effective cellular immune response and a humoral immune response owing to their natural adjuvant properties via transduction of immune cells. Consequently, viral vectored vaccines carrying the SARS-CoV-2 spike protein have recently been generated and successfully used to activate cytotoxic T cells and develop a neutralizing antibody response. Recent progress in SARS-CoV-2 vaccines, with an emphasis on gene therapy viral vector-based vaccine development, is discussed in this review.

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“…Many viral vectors, when coupled with tissue-specific promoters, can deliver insulin very efficiently into target sites such as the liver, 84 skeletal muscle, 85 and pancreas. 86 Lentiviral vector integrates into the genome and expresses the transgene stably. 74,[86][87][88] Non-integrative adenovirus can last for at most a few months.…”

Section: Reviewmentioning

confidence: 99%

“…86 Lentiviral vector integrates into the genome and expresses the transgene stably. 74,[86][87][88] Non-integrative adenovirus can last for at most a few months. 71,77,[89][90][91][92][93] While adeno-associated virus (AAV) and AAV hybrid vectors are more long-lasting, 76,80,81 they prevent re-administration as a top-up strategy due to antibodies formed against the viral vectors.…”

Section: Reviewmentioning

confidence: 99%

Charting the next century of insulin replacement with cell and gene therapies

Lau

Shen

Lickert

et al. 2021

Med

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The discovery of insulin a century ago changed the lives of millions of individuals suffering from diabetes, paving the way for long-term survival. While the availability of recombinant insulin for hormone replacement therapy has served extremely well to help control blood glucose in diabetes, there remains significant room for further improvements for an ultimate ''cure'' for diabetes patients. In this review, we celebrate the 100th anniversary of the discovery of insulin and consolidate the key milestones and advances in the development of recombinant human insulin. We then summarize recent and current technological developments in terms of insulin gene-and cell-replacement therapies that are promising in greater therapeutic potential. We envision that the next era of insulin replacement therapies will effectively treat diabetes and serve our patients even better for the next century to come.

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Lentivirus Mediated Pancreatic Beta-Cell-Specific Insulin Gene Therapy for STZ-Induced Diabetes

Cited by 14 publications

References 64 publications

Genome engineering and disease modeling via programmable nucleases for insulin gene therapy; promises of CRISPR/Cas9 technology

Genome engineering and disease modeling via programmable nucleases for insulin gene therapy; promises of CRISPR/Cas9 technology

Current Update on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development with a Special Emphasis on Gene Therapy Viral Vector Design and Construction for Vaccination

Charting the next century of insulin replacement with cell and gene therapies

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