Neutral Lipopolyplexes for In Vivo Delivery of Conventional and Replicative RNA Vaccine

Perche, Federico; Clemençon, Rudy; Schulze, Kai; Ebensen, Thomas; Guzmán, Carlos A.; Pichon, Chantal

doi:10.1016/j.omtn.2019.07.014

Cited by 46 publications

(54 citation statements)

References 81 publications

(235 reference statements)

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“…The results showed that intravenous injection of neutral mannosylated lipopolyplex–mRNA complexes led to reporter protein expression in mice. Intramuscular injection of neutral mannosylated lipopolyplex–SAM RNA complexes encoding an influenza antigen led to sustained gene expression in vivo and induced functional antigen-specific T cells [ 68 ].…”

Section: Mrna-based Vaccines’ Nanodelivery Systemsmentioning

confidence: 99%

Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

et al. 2020

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Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.

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Section: Mrna-based Vaccines’ Nanodelivery Systemsmentioning

confidence: 99%

Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

et al. 2020

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“… Mice/G. pig Protection against lethal ZIKV challenge [ 33 •• ] Neutral LPP GFP/Luc/HA Mouse Specific and functional T cell responses [ 32 • ] CAFs/PEI Chlamydia ag. Immune responses, unaffected by TLR-agonists [ 36 ] pABOL HA Protection from influenza virus challenge [ 40 ] CNE VEEV TC-83 Full protection against VEEV challenge [ 30 •• ] cVEEV Viral ag.…”

Section: Vaccines Based On Naked Sarnamentioning

confidence: 99%

“…Since APCs express significant amounts of mannose receptors on their surface, this strategy increased humoral and cellular responses against influenza hemagglutinin (HA) expressed from a saRNA. A similar approach has been used by Perche et al [ 32 • ] using neutral lipopolyplexes (LPPs), a tripartite formulation with saRNA, a cationic polymer, and anionic liposomes, including a mannosylated lipid to enhance transfection of dendritic cells (DCs).…”

Section: Vaccines Based On Sarna Conjugated To Lnpsmentioning

confidence: 99%

A new generation of vaccines based on alphavirus self-amplifying RNA

Ballesteros-Briones

Silva-Pilipich

Herrador

et al. 2020

Current Opinion in Virology

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Highlights Alphavirus self-amplifiying RNA (saRNA) induces more potent immune responses than conventional mRNA. saRNA delivery can be enhanced by electroporation or conjugation with cationic lipid or polymers. saRNA vaccines induce protective responses against human pathogens in preclinical models. saRNA replication mediates innate immune signals that contribute to the strength of immune responses. saRNA vaccines could be generated in a quick way to face emergent pathogens like SARS-CoV-2.

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“…Molecules 2020, 25, x FOR PEER REVIEW 2 of 17 can be modularly selected to adapt the formulation to the particular needs of many pathological scenarios. Thus, they have been used for producing nanovaccines [15], for the treatment of neurodegenerative diseases [8], and especially for cancer treatment [16][17][18][19][20][21][22]. When a novel gene delivery formulation is prepared, one of the first steps to test their therapeutic potential is to evaluate their gene transfection capacity in vitro [23].…”

Section: Introductionmentioning

confidence: 99%

“…LPPs provide great versatility, since a wide range of different lipids, polymers and nucleic acids can be modularly selected to adapt the formulation to the particular needs of many pathological scenarios. Thus, they have been used for producing nanovaccines [ 15 ], for the treatment of neurodegenerative diseases [ 8 ], and especially for cancer treatment [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of Lipopolyplexes for Gene Transfection: Comparing 2D, 3D and Microdroplet-Enabled Cell Culture

et al. 2020

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Complexes combining nucleic acids with lipids and polymers (lipopolyplexes) show great promise for gene therapy since they enable compositional, physical and functional versatility to be optimized for therapeutic efficiency. When developing lipopolyplexes for gene delivery, one of the first evaluations performed is an in vitro transfection efficiency experiment. Many different in vitro models can be used, and the effect of the model on the experiment outcome has not been thoroughly studied. The objective of this work was to compare the insights obtained from three different in vitro models, as well as the potential limitations associated with each of them. We have prepared a series of lipopolyplex formulations with three different cationic polymers (poly-l-lysine, bioreducible poly-l-lysine and polyethyleneimine), and assessed their in vitro biological performance in 2D monolayer cell culture, 3D spheroid culture and microdroplet-based single-cell culture. Lipopolyplexes from different polymers presented varying degrees of transfection efficiency in all models. The best-performing formulation in 2D culture was the polyethyleneimine lipopolyplex, while lipoplexes prepared with bioreducible poly-l-lysine were the only ones achieving any transfection in microdroplet-enabled cell culture. None of the prepared formulations achieved significant gene transfection in 3D culture. All of the prepared formulations were well tolerated by cells in 2D culture, while at least one formulation (poly-l-lysine polyplex) delayed 3D spheroid growth. These results highlight the need for selecting the appropriate in vitro model depending on the intended application.

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Neutral Lipopolyplexes for In Vivo Delivery of Conventional and Replicative RNA Vaccine

Cited by 46 publications

References 81 publications

Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

A new generation of vaccines based on alphavirus self-amplifying RNA

In Vitro Evaluation of Lipopolyplexes for Gene Transfection: Comparing 2D, 3D and Microdroplet-Enabled Cell Culture

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