Lipid‐Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery

Zhang, Yunlong; Pelet, Jeisa M.; Heller, Daniel A.; Dong, Yizhou; Chen, Delai; Gu, Zhen; Joseph, Brian; Wallas, Jasmine; Anderson, Daniel G.

doi:10.1002/adma.201301917

Cited by 36 publications

(35 citation statements)

References 43 publications

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“…In order to explore the broad chemical space of lipids, Anderson and Langer synthesized over one thousands of lipid derivatives (also termed as lipid-like molecules or lipidoids) using a combinatorial approach (Akinc et al, 2008). These lipids consist of multiple hydrophilic groups and several lipid tails, which were widely used for siRNA delivery (Akinc et al, 2008;Alabi et al, 2013;Dong, Eltoukhy, et al, 2014;Dong, Love, et al, 2014;Whitehead et al, 2014;Zhang et al, 2013). Based on C12-200 (Love et al, 2010), Kauffman et al (2015) optimized its formulation using Design of Experiment methodologies and increased sevenfold of erythropoietin expression compared to the original formulation.…”

Section: Lipid and Lipid-derived Nanoparticles For Mrna Deliverymentioning

confidence: 99%

Nanoscale platforms for messenger RNA delivery

Zhang

Dong

2018

WIREs Nanomed Nanobiotechnol

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141

142

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Messenger RNA (mRNA) has become a promising class of drugs for diverse therapeutic applications in the past few years. A series of clinical trials are ongoing or will be initiated in the near future for the treatment of a variety of diseases. Currently, mRNA-based therapeutics mainly focuses on ex vivo transfection and local administration in clinical studies. Efficient and safe delivery of therapeutically relevant mRNAs remains one of the major challenges for their broad applications in humans. Thus, effective delivery systems are urgently needed to overcome this limitation. In recent years, numerous nanoscale biomaterials have been constructed for mRNA delivery in order to protect mRNA from extracellular degradation and facilitate endosomal escape after cellular uptake. Nanoscale platforms have expanded the feasibility of mRNA-based therapeutics, and enabled its potential applications to protein replacement therapy, cancer immunotherapy, therapeutic vaccines, regenerative medicine, and genome editing. This review focuses on recent advances, challenges, and future directions in nanoscale platforms designed for mRNA delivery, including lipid and lipid-derived nanoparticles, polymer-based nanoparticles, protein derivatives mRNA complexes, and other types of nanomaterials. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.

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Section: Lipid and Lipid-derived Nanoparticles For Mrna Deliverymentioning

confidence: 99%

Nanoscale platforms for messenger RNA delivery

Zhang

Dong

2018

WIREs Nanomed Nanobiotechnol

Self Cite

141

142

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“…The multiple amino groups in the aminoglycoside structure were used as attachment points for hydrophobic lipid tails. A library of lipid modified aminoglycosides was prepared by a single step reaction of epoxides with commercially available aminoglycosides ( Figure ). The lipid modified aminoglycosides were screened using luciferase reporter system in HeLa cells.…”

Section: Combinatorial Approach To Cationic Lipidoid/peptoid‐based Namentioning

confidence: 99%

Combinatorial Approach to Nanoarchitectonics for Nonviral Delivery of Nucleic Acids

Molla

Levkin

2015

Advanced Materials

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Nanoparticles based on cationic polymers, lipids or lipidoids are of great interest in the field of gene delivery applications. The research on these nanosystems is rapidly growing as they hold promise to treat wide variety of human diseases ranging from viral infections to genetic disorders and cancer. Recently, combinatorial design principles have been adopted for rapid generation of large numbers of chemically diverse polymers and lipids capable of forming multifunctional nanocarriers for the use in gene delivery applications. At the same time, current high-throughput screening systems as well as convenient cell assays and readout techniques allow for fast evaluation of cell transfection efficiencies and toxicities of libraries of novel gene delivery agents. This allows for a rapid evaluation of structure-function relationship as well as identification of novel efficient nanocarriers for cell transfection and gene therapy. This progress report describes the recent contribution of high-throughput synthesis to the development of novel nanocarriers for gene delivery applications.

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“…Cytotoxicity of cationic lipids and polymers is an important limiting factor. Combinatorial synthesis and high throughput screening have been utilized to generate low-toxicity lipids for siRNA delivery to liver [173, 174]. Efficient target gene silence also requires the timely release of siRNA into cytoplasm.…”

Section: Future Directionsmentioning

confidence: 99%

Recent In Vivo Evidences of Particle-Based Delivery of Small-Interfering RNA (siRNA) into Solid Tumors

Wen

Meng

2014

J Pharm Innov

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Small-interfering RNA (siRNA) is both a powerful tool in research and a promising therapeutic platform to modulate expression of disease-related genes. Malignant tumors are attractive disease targets for nucleic acid-based therapies. siRNA directed against oncogenes, and genes driving metastases or angiogenesis have been evaluated in animal models and in some cases, in humans. The outcomes of these studies indicate that drug delivery is a significant limiting factor. This review provides perspectives on in vivo validated nanoparticle-based siRNA delivery systems. Results of recent advances in liposomes and polymeric and inorganic formulations illustrate the need for mutually optimized attributes for performance in systemic circulation, tumor interstitial space, plasma membrane, and endosomes. Physiochemical properties conducive to efficient siRNA delivery are summarized and directions for future research are discussed.

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Lipid‐Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery

Cited by 36 publications

References 43 publications

Nanoscale platforms for messenger RNA delivery

Nanoscale platforms for messenger RNA delivery

Combinatorial Approach to Nanoarchitectonics for Nonviral Delivery of Nucleic Acids

Recent In Vivo Evidences of Particle-Based Delivery of Small-Interfering RNA (siRNA) into Solid Tumors

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