Composite liposome-PEI/nucleic acid lipopolyplexes for safe and efficient gene delivery and gene knockdown

Pinnapireddy, Shashank Reddy; Duse, Lili; Strehlow, Boris

doi:10.1016/j.colsurfb.2017.06.022

Cited by 78 publications

(63 citation statements)

References 27 publications

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“…However, they suffer from relatively low loading capacity for siRNA and premature leakage of payloads, and they require additional cationic materials to condense the highly anionic payloads into the liposomal core. Commonly used condensers include protamine, peptides, and polyethylenimine (PEI) …”

Section: Protective Carriers For Sirna Deliverymentioning

confidence: 99%

“…Various fusogenic liposome compositions have been developed, although they were initially intended for biological studies on membrane fusion, rather than for siRNA delivery . The most widely used compositions contain 1,2‐dioleoyl‐3‐glycero‐phosphatidylethanolamine (DOPE), and a cationic lipid such as N‐[1‐(2,3‐dioleoyloxy)propyl]‐N,N,N‐trimethyammonium chloride (DOTMA), or 1,2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) . While the exact mechanism and role of these lipids are not clear, it is theorized that a mix of aromatic molecule, cationic surface charge, and conical lipid structure are involved in membrane fusion .…”

Section: Strategies Against Endocytosismentioning

confidence: 99%

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Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201903637.With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.

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Section: Protective Carriers For Sirna Deliverymentioning

confidence: 99%

Section: Strategies Against Endocytosismentioning

confidence: 99%

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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“…However, a universally applicable transfection strategy that combines high bioavailability, low toxicity, and highest transfer efficiency has yet to be developed. In general, there are two main routes toward transfection: the chemical route based on nanoparticles or liposomaland polymer-based formulations [1][2][3][4][5], and the viral route, where the viral envelope serves as carrier vehicle [6,7].…”

Section: Introductionmentioning

confidence: 99%

Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes

Hoffmann

Hersch

Gerlach

et al. 2020

IJMS

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Highly efficient, biocompatible, and fast nucleic acid delivery methods are essential for biomedical applications and research. At present, two main strategies are used to this end. In non-viral transfection liposome- or polymer-based formulations are used to transfer cargo into cells via endocytosis, whereas viral carriers enable direct nucleic acid delivery into the cell cytoplasm. Here, we introduce a new generation of liposomes for nucleic acid delivery, which immediately fuse with the cellular plasma membrane upon contact to transfer the functional nucleic acid directly into the cell cytoplasm. For maximum fusion efficiency combined with high cargo transfer, nucleic acids had to be complexed and partially neutralized before incorporation into fusogenic liposomes. Among the various neutralization agents tested, small, linear, and positively charged polymers yielded the best complex properties. Systematic variation of liposomal composition and nucleic acid complexation identified surface charge as well as particle size as essential parameters for cargo-liposome interaction and subsequent fusion induction. Optimized protocols were tested for the efficient transfer of different kinds of nucleic acids like plasmid DNA, messenger RNA, and short-interfering RNA into various mammalian cells in culture and into primary tissues.

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“…A fully deacylated 22kDa variant of linear PEI containing 11% more protonable nitrogens was used for polyplex formation with luciferase expressing pCMV-luc plasmid. Lipopolyplexes were prepared as previously described [26]. Briefly, both polyplexes and liposomes (mass ratio 1:0.5) were mixed vigorously and incubated for 1h at room temperature to facilitate lipopolyplexes formation.…”

Section: Methodsmentioning

confidence: 99%

Composite liposome-PEI/nucleic acid lipopolyplexes for safe and efficient gene delivery and gene knockdown

Cited by 78 publications

References 27 publications

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes

Photo-Enhanced Delivery of Genetic Material Using Curcumin Loaded Composite Nanocarriers

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