ArticleBioorganic & medicinal chemistry2014
Chemically defined polyethylene glycol siRNA conjugates with enhanced gene silencing effect.
Article in Bioorganic & medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Review
- Advancements in small interfering RNAs therapy for acute lymphoblastic leukemia: promising results and future perspectives.Molecular biology reports · 2024Review
- Striving for Uniformity: A Review on Advances and Challenges To Achieve Uniform Polyethylene Glycol.Organic process research & development · 2024Review
- The emerging potential of siRNA nanotherapeutics in treatment of arthritis.Asian journal of pharmaceutical sciences · 2023Review
- PK-modifying anchors significantly alter clearance kinetics, tissue distribution, and efficacy of therapeutics siRNAs.Molecular therapy. Nucleic acids · 2022Article
- Use of Protamine in Nanopharmaceuticals-A Review.Nanomaterials (Basel, Switzerland) · 2021Review
- Cell-Penetrating Peptides Delivering siRNAs: An Overview.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Current Aspects of siRNA Bioconjugate for In Vitro and In Vivo Delivery.Molecules (Basel, Switzerland) · 2019Review
- Therapeutic potential of chemically modified siRNA: Recent trends.Chemical biology & drug design · 2017Review
- Oligonucleotides conjugated with short chemically defined polyethylene glycol chains are efficient antisense agents.Bioorganic & medicinal chemistry letters · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
The therapeutic application of siRNA suffers from poor bioavailability caused by rapid degradation and elimination. The covalent attachment of PEG is a universal concept to increase molecular size and enhance the pharmacokinetic properties of biomacromolecules. We devised a facile approach for attachment of PEG molecules with a defined molecular weight, and successful purification of the resulting conjugates. We directly conjugated structurally defined PEG chains with twelve ethylene glycol units to the 3'-terminal hydroxyl group of both sense and antisense strands via an aminoalkyl linker. The conjugates were easily purified by HPLC and successful PEGylation and molecule integrity were confirmed by ESI-MS. The evaluation of in vitro gene knockdown of two different targets in MCF-7 breast cancer cells showed stable pharmacologic activity when combined with a standard transfection reagent. Sense strand PEGylation even increased the silencing potency of a CRCX4-siRNA which had modest activity in its wild-type form. The results indicate that PEG chains at the 3'-terminus of both strands of siRNA are well tolerated by the RNAi effector. The attachment of short, chemically defined PEG chains is a feasible approach to improve the pharmacokinetic properties of siRNA, and can be combined with other targeted and untargeted delivery vehicles.
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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.