ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Embedding siRNA sequences targeting apolipoprotein B100 in shRNA and miRNA scaffolds results in differential processing and in vivo efficacy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Clinical Proof-of-Concept of a Non-Gene Editing Technology Using miRNA-Based shRNA to Engineer Allogeneic CAR T-Cells.International journal of molecular sciences · 2025Article
- Engineering strategies to safely drive CAR T-cells into the future.Frontiers in immunology · 2024Review
- Efficient shRNA-based knockdown of multiple target genes for cell therapy using a chimeric miRNA cluster platform.Molecular therapy. Nucleic acids · 2023Article
- Broadening the Horizons of RNA Delivery Strategies in Cancer Therapy.Bioengineering (Basel, Switzerland) · 2022Review
- Efficient and Precise Processing of the Optimized Primary Artificial MicroRNA in a Huntingtin-Lowering Adeno-Associated Viral Gene TherapyHuman gene therapy · 2022Article
- Antiviral efficacy of short-hairpin RNAs and artificial microRNAs targeting foot-and-mouth disease virus.PeerJ · 2021Article
- Effective and Accurate Gene Silencing by a Recombinant AAV-Compatible MicroRNA Scaffold.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Optimizing Synthetic miRNA Minigene Architecture for Efficient miRNA Hairpin Concatenation and Multi-target Gene Knockdown.Molecular therapy. Nucleic acids · 2019Article
- TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus.Nucleic acids research · 2017Article
- A new design of a lentiviral shRNA vector with inducible co-expression of ARGONAUTE 2 for enhancing gene silencing efficiency.Cell & bioscience · 2015Article
- Artificial MiRNA Knockdown of Platelet Glycoprotein lbα: A Tool for Platelet Gene Silencing.PloS one · 2015Article
- Recombinant AAV as a platform for translating the therapeutic potential of RNA interference.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Review
- Lentiviral vector-mediated RNA silencing in the central nervous system.Human gene therapy methods · 2014Review
- Therapeutic expression of hairpins targeting apolipoprotein B100 induces phenotypic and transcriptome changes in murine liver.Gene therapy · 2014Article
- Article
- Modulators of the microRNA biogenesis pathway via arrayed lentiviral enabled RNAi screening for drug and biomarker discovery.Combinatorial chemistry & high throughput screening · 2013Article
- Long-term Expression of Apolipoprotein B mRNA-specific Hammerhead Ribozyme via scAAV8.2 Vector Inhibits Atherosclerosis in Mice.Molecular therapy. Nucleic acids · 2013Article
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression of short hairpin RNA (shRNA) often causes cytotoxicity and using microRNA (miRNA) scaffolds can circumvent this problem. In this study, identically predicted small interfering RNA (siRNA) sequences targeting apolipoprotein B100 (siApoB) were embedded in shRNA (shApoB) or miRNA (miApoB) scaffolds and a direct comparison of the processing and long-term in vivo efficacy was performed. Next generation sequencing of small RNAs originating from shApoB- or miApoB-transfected cells revealed substantial differences in processing, resulting in different siApoB length, 5' and 3' cleavage sites and abundance of the guide or passenger strands. Murine liver transduction with adeno-associated virus (AAV) vectors expressing shApoB or miApoB resulted in high levels of siApoB expression associated with strong decrease of plasma ApoB protein and cholesterol. Expression of miApoB from the liver-specific LP1 promoter was restricted to the liver, while the H1 promoter-expressed shApoB was ectopically present. Delivery of 1 × 10(11) genome copies AAV-shApoB or AAV-miApoB led to a gradual loss of ApoB and plasma cholesterol inhibition, which was circumvented by delivering a 20-fold lower vector dose. In conclusion, incorporating identical siRNA sequences in shRNA or miRNA scaffolds results in differential processing patterns and in vivo efficacy that may have serious consequences for future RNAi-based therapeutics.
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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.