Biopolymer‐based Carriers for DNA Vaccine Design

Franck, Christoph O.; Fanslau, Luise; Bistrović, Andrea; Tyagi, Puneet; Fruk, Ljiljana

doi:10.1002/anie.202010282

Cited by 46 publications

(34 citation statements)

References 238 publications

(193 reference statements)

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“…For pDNA vaccines, the plasmid DNA needs to enter the nucleus to produce the protein that will then elicit an immune response through antigen-presenting cells, such as dendritic cells (60). There remain no DNA vaccines approved for human use in the USA, but these have had success in veterinary medicine (61,62). As such, it is possible that these vaccines will be the next major milestone for human immunizations.…”

Section: Discussionmentioning

confidence: 99%

Encapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In Vivo

et al. 2021

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Encapsulating genetic material into biocompatible polymeric microparticles is a means to improving gene transfection while simultaneously decreasing the tendency for inflammatory responses; and can be advantageous in terms of delivering material directly to the lungs via aerosolization for applications such as vaccinations. In this study, we investigated the advantages of using polymeric microparticles carrying the luciferase reporter gene in increasing transfection efficiency in the readily transfectable HEK293 cell line and the difficult to transfect RAW264.7 cell line. The results indicated that there was a limit to the ratio of nitrogen in polyethylenimine (PEI) to phosphate in DNA (N/P ratio) beyond which further increases in transgene expression no longer, or only marginally, occurred. Microparticles encapsulating PEI:DNA nanoplexes induced cellular toxicity in a dose-dependent manner. PEGylation increased transgene expression, likely related to enhanced degradation of particles. Furthermore, intra-tracheal instillation in rats allowed us to investigate the inflammatory response in the lung as a function of PEGylation, porosity, and size. Porosity did not influence cell counts in bronchoalveolar lavage fluid in the absence of PEG, but in particles containing PEG, non-porous particles recruited fewer inflammatory cells than their porous counterparts. Finally, both 1 μm and 10 μm porous PLA-PEG particles recruited more neutrophils than 4 μm particles. Thus, we have shown that PEGylation and lack of porosity are advantageous for faster release of genetic cargo from microparticles and a reduced inflammatory response, respectively. Supplementary Information The online version contains supplementary material available at 10.1208/s12249-021-01932-z.

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Section: Discussionmentioning

confidence: 99%

Encapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In Vivo

et al. 2021

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“…Guanidino groups were chosen as they are known to increase membrane coordination and penetration through strong guanidinium-phosphate H-bonding. This interaction has been demonstrated to be key to the activity of arginine rich antimicrobial peptides 52 and cell penetrating peptides, [53][54][55][56][57] which we hypothesised would enhance PDI efficacy. The UV-Vis absorption spectra of the flavins in DMSO revealed very similar absorption properties at the λ1 (S0→S1) band but a blue shift of 10-13 nm for the higher energy λ2 (S0→S2) bands of the brominated compounds (F3 and F4) presumably due to the electron withdrawing effect of Br atoms (Figure 2b, Table 1).…”

Section: Synthesis and Characterisation Of Flavinsmentioning

confidence: 95%

Tuning Riboflavin Derivatives For Photodynamic Inactivation of Pathogens

Fruk

Crocker

Lee

et al. 2021

Preprint

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The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin’s visible light-iinduced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives’ toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.

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“…Polysaccharides are a group of carbohydrate compounds that are generally regarded as safe (GRAS) with limited risk of toxic metabolites or long-term deposits of tissues and are biocompatible. As summarized in Table 1, [21][22][23][24] due to their size, molecular weight, and chemical structure, many carbohydrate polymers play important signaling roles within the immune system by targeting various immune cells and are also capable of stabilizing biomolecules against thermal degradation and agitation. Some naturally occurring polymers such as chitosan, glucan (like dextran), inulin, and other forms of polymers including non-ionic block copolymers that are anticipated to express the proposed dual role are detailed below.…”

Section: Overview Of Carbohydrate Polymers With Dual-rolementioning

confidence: 99%

Biopolymers and Osmolytes — A Focus towards the Prospects of Stability and Adjuvanticity of Vaccines

2022

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‘New-Gen Vaccines’ are grabbing the attention of scientists as they are much suitable for an immune-compromised group of individuals as well as infants. The major drawbacks of these vaccines are lower immunogenicity and instability. The need for a convenient and safe adjuvant is still under exploration. On the other hand, thermal instability leads to the inactivation of the vaccine and becomes detrimental in many cases. Thus, there is a need to incorporate new kinds of excipients into vaccine formulation to enhance the potency/immunogenicity of vaccine antigens and also act as stabilizers. A limited or single excipient in providing the required dual-activity is vital to break the stereotypical usage of the well-entrenched adverse ingredients. In the proposed review, the efficiency of naturally occurring biocompatible carbohydrate polymers and osmolytes and their ‘dual-role’ is briefed. In addition, the information on the possible mechanisms of action of carbohydrate polymers in vaccines as adjuvants and stabilizers are also discussed.

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Biopolymer‐based Carriers for DNA Vaccine Design

Cited by 46 publications

References 238 publications

Encapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In Vivo

Encapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In Vivo

Tuning Riboflavin Derivatives For Photodynamic Inactivation of Pathogens

Biopolymers and Osmolytes — A Focus towards the Prospects of Stability and Adjuvanticity of Vaccines

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