ArticleStem cells translational medicine2013
Sustained knockdown of a disease-causing gene in patient-specific induced pluripotent stem cells using lentiviral vector-based gene therapy.
Article in Stem cells translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- EF-1α-driven nanobody-based CD19-redirected CAR-T cells retain the antitumor efficacy, antigen-driven expansion, and cytokine secretion of CMV-driven counterparts.Molecular and cellular biochemistry · 2026Article
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine.Current medicinal chemistry · 2024Review
- Future Perspectives in the Diagnosis and Treatment of Liver Disease Associated with Alpha-1 Antitrypsin Deficiency.GE Portuguese journal of gastroenterology · 2023Review
- Protocol for a Wnt reporter assay to measure its activity in human neural stem cells derived from induced pluripotent stem cells.Current research in neurobiology · 2023Article
- A selectable all-in-one CRISPR prime editing piggyBac transposon allows for highly efficient gene editing in human cell lines.Scientific reports · 2021Article
- [Research progress of hepatocyte transplantation treatment for alpha-1 antitrypsin deficiency].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression.PloS one · 2020Article
- Endogenous APOBEC3B Overexpression Constitutively Generates DNA Substitutions and Deletions in Myeloma Cells.Scientific reports · 2019Article
- Current Perspectives Regarding Stem Cell-Based Therapy for Liver Cirrhosis.Canadian journal of gastroenterology & hepatology · 2018Review
- Liver Disease in Alpha-1 Antitrypsin Deficiency: Current Approaches and Future Directions.Current pathobiology reports · 2017Review
- Improved bi-allelic modification of a transcriptionally silent locus in patient-derived iPSC by Cas9 nickase.Scientific reports · 2016Article
- The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases.Current protocols in toxicology · 2016Review
- Stem Cell Therapies for Treatment of Liver Disease.Biomedicines · 2016Review
- Current status of pluripotent stem cells: moving the first therapies to the clinic.Nature reviews. Drug discovery · 2015Review
- Induced pluripotent stem cells model personalized variations in liver disease resulting from α1-antitrypsin deficiency.Hepatology (Baltimore, Md.) · 2015Article
- Liver-targeted gene therapy: Approaches and challenges.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2015Review
- Investigating human disease using stem cell models.Nature reviews. Genetics · 2014Review
- Induced pluripotent stem cells in hematology: current and future applications.Blood cancer journal · 2014Review
- A Comparative View on Human Somatic Cell Sources for iPSC Generation.Stem cells international · 2014Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for studies on disease-related developmental processes and may serve as an autologous cell source for future treatment of many hereditary diseases. New genetic engineering tools such as zinc finger nucleases and transcription activator-like effector nuclease allow targeted correction of monogenetic disorders but are very cumbersome to establish. Aiming at studies on the knockdown of a disease-causing gene, lentiviral vector-mediated expression of short hairpin RNAs (shRNAs) is a valuable option, but it is limited by silencing of the knockdown construct upon epigenetic remodeling during differentiation. Here, we propose an approach for the expression of a therapeutic shRNA in disease-specific iPSCs using third-generation lentiviral vectors. Targeting severe α-1-antitrypsin (A1AT) deficiency, we overexpressed a human microRNA 30 (miR30)-styled shRNA directed against the PiZ variant of A1AT, which is known to cause chronic liver damage in affected patients. This knockdown cassette is traceable from clonal iPSC lines to differentiated hepatic progeny via an enhanced green fluorescence protein reporter expressed from the same RNA-polymerase II promoter. Importantly, the cytomegalovirus i/e enhancer chicken β actin (CAG) promoter-driven expression of this construct is sustained without transgene silencing during hepatic differentiation in vitro and in vivo. At low lentiviral copy numbers per genome we confirmed a functional relevant reduction (-66%) of intracellular PiZ protein in hepatic cells after differentiation of patient-specific iPSCs. In conclusion, we have demonstrated that lentiviral vector-mediated expression of shRNAs can be efficiently used to knock down and functionally evaluate disease-related genes in patient-specific iPSCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.