Combinatorial Library of Lipidoids for In Vitro DNA Delivery

Sun, Shuo; Wang, Ming; Knupp, Sarah A.; Soto‐Feliciano, Yadira M.; Hu, Xiao; Kaplan, David L.; Langer, Robert; Anderson, Daniel G.; Xu, Qiaobing

doi:10.1021/bc200572w

Cited by 75 publications

(65 citation statements)

References 18 publications

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“…Lipidoid 14N-87 109c was able to encapsulate up to 70% DNA, while 14O-87 109l and 16C-87 109z were able to encapsulate 82% and respectively 55%, as revealed by a picogreen assay. 186 108g, 109g, 110b and 111b. Moreover, the same unsaturated lipidoids were found at least 50% more efficient than LFM2000 for mRNA delivery into HeLa cells, but were found less potent than the commercial transfection system in delivering DNA in the same cell line.…”

Section: Oligomeric Amphiphilesmentioning

confidence: 99%

Synthetic Nucleic Acid Delivery Systems: Present and Perspectives

Draghici

Ilies

2015

J. Med. Chem.

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Self-assembled synthetic gene delivery systems represent the bottom-up approach to gene delivery and gene silencing, in which scientists are designing novel cationic and procationic amphiphiles that can pack, transport, and deliver nucleic acids to various targets in the body in a controlled manner. These supramolecular assemblies are safer than viruses, but they are lagging behind them in efficiency. We are presenting recent progress that has narrowed this gap through better understanding the delivery barriers and incorporation of this knowledge in the design of novel synthetic amphiphiles, formulations, and revolutionary screening and optimization processes. Structure-properties and structure-activity relationships were drawn within each amphiphile class, presenting the cellular and animal models used to generate them. We are also revealing pertinent in vitro/in vivo correlations that emphasize promising amphiphiles and successful formulation optimization efforts for efficient in vivo nucleic acid delivery, together with main organ targets and diseases treatable with these revolutionary technologies.

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Section: Oligomeric Amphiphilesmentioning

confidence: 99%

Synthetic Nucleic Acid Delivery Systems: Present and Perspectives

Draghici

Ilies

2015

J. Med. Chem.

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“…Recently, we developed lipid-like nanoparticles that can be synthesized in a combinatorial manner as highly effective protein and gene delivery vehicles (9)(10)(11)(12)(13). We found that electrostatic selfassembly between lipid and protein is essential to form a stable nanocomplex for protein delivery (11).…”

mentioning

confidence: 99%

Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

Wang

Zuris

Meng

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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528

473

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A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing.

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“…The cationic poly(-amino ester) library of over 5,000 different constituents was then screened for use in non-viral gene therapy using plasmid DNA and siRNA delivery. Selection of "hits" from the poly(-amino ester) library allowed for further modification of the backbone structure to include lipid functionality and formulation of lipidoid-based nano-vesicles for siRNA encapsulation (10,(19)(20)(21).…”

Section: Combinatorial-designed Nanoparticlesmentioning

confidence: 99%

Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

Amiji

2016

SPIE Proceedings

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Recent advances in biomedical sciences, especially in the field of human genetics, is increasingly considered to facilitate a new frontier in development of novel disease-modifying therapeutics. One of major challenges in the development of nucleic acid therapeutics is efficient and specific delivery of the molecules to the target tissue and cell upon systemic administration. In this report, I discuss our strategy to develop combinatorial-designed multifunctional nanoparticle assemblies based on natural biocompatible and biodegradable polymers for nucleic acid delivery in: (1) overcoming tumor drug resistance and (2) genetic modulation of macrophage functional phenotype from M1 to M2 in treatment of inflammatory diseases.

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Combinatorial Library of Lipidoids for In Vitro DNA Delivery

Cited by 75 publications

References 18 publications

Synthetic Nucleic Acid Delivery Systems: Present and Perspectives

Synthetic Nucleic Acid Delivery Systems: Present and Perspectives

Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

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