Discovery of Cationic Polymers for Non-Viral Gene Delivery Using Combinatorial Approaches

Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang‐Chiao; Montanez, Gabriela; Rege, Kaushal

doi:10.2174/138620711797537076

Cited by 65 publications

(29 citation statements)

References 80 publications

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“…Combinatorial / parallel syntheses are commonly employed for generating libraries of small molecules as drug candidates[31, 32], and have been extended to facilitate the rapid discovery of polymers for transgene delivery and expression[33, 34]. In this work, we investigated aminoglycoside antibiotics as monomers in the parallel synthesis of polymers for transgene delivery to mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling

et al. 2014

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We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and ‘building block’ polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology.

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Section: Introductionmentioning

confidence: 99%

Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling

et al. 2014

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“…The researchers concluded that this approach promotes the escape of gold nanoparticle/nucleic acid complexes from the endosome/lysosome and release of oligonucleotides into the cytoplasm. Combinatorial synthesis and parallel screening approaches can help identify candidate polymers that have high gene delivery and gene silencing efficacies [86,133].…”

Section: Electrostatic Interactions Between the Positively Charged Namentioning

confidence: 99%

Oligonucleotide-Based Theranostic Nanoparticles in Cancer Therapy

Shahbazi

Özpolat

Ulubayram

2016

Nanomedicine (Lond.)

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Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics.

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“…[26] Cationic polymers allow the carried DNA to be condensed through electrostatic interactions and transport them by ligands, containing cell-targeting molecules, attached to the polymer’s functional group. [27–29] While their cell-targeting capabilities are a great improvement when compared to viral-vectors, their transfection efficiency can be hindered; nonetheless, poly(ethylenimine) (PEI)-based polyplexes have greater gene transfer success than HIV-derived vectors and share similar results to adenoviral vectors. [30] PEIs are attractive nonviral vectors because they show an increase in protection, cell binding, and uptake due to endosomal escape and exhibit the ability to deliver cargo (DNA, siRNA) efficiently.…”

Section: Introductionmentioning

confidence: 99%

Current status of non-viral gene therapy for CNS disorders

Jayant

Sosa

Kaushik

et al. 2016

Expert Opinion on Drug Delivery

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Introduction Viral and non-viral vectors have been used as methods of delivery in gene therapy for many CNS diseases. Currently, viral vectors such as adeno-associated viruses (AAV), retroviruses, lentiviruses, adenoviruses and herpes simplex viruses (HHV) are being used as successful vectors in gene therapy at clinical trial levels. However, many disadvantages have risen from their usage. Non-viral vectors like cationic polymers, cationic lipids, engineered polymers, nanoparticles, and naked DNA offer a much safer option and can therefore be explored for therapeutic purposes. Areas covered This review discusses different types of viral and non-viral vectors for gene therapy and explores clinical trials for CNS diseases that have used these types of vectors for gene delivery. Highlights include non-viral gene delivery and its challenges, possible strategies to improve transfection, regulatory issues concerning vector usage, and future prospects for clinical applications. Expert opinion Transfection efficiency of cationic lipids and polymers can be improved through manipulation of molecules used. Efficacy of cationic lipids is dependent on cationic charge, saturation levels, and stability of linkers. Factors determining efficacy of cationic polymers are total charge density, molecular weights, and complexity of molecule. All of the above mentioned parameters must be taken care for efficient gene delivery.

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Discovery of Cationic Polymers for Non-Viral Gene Delivery Using Combinatorial Approaches

Cited by 65 publications

References 80 publications

Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling

Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling

Oligonucleotide-Based Theranostic Nanoparticles in Cancer Therapy

Current status of non-viral gene therapy for CNS disorders

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