Peptide-based DNA delivery system

Somvanshi, Pranjal; Khisty, Shefali

doi:10.1016/j.medntd.2021.100091

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Both viral and non-viral transfection vectors have been used in the past. Despite the usual higher gene transfer efficacies of viral vectors compared to their nonviral counterparts, immunogenicity related toxic side effects of the viral vectors [16] are increasingly making non-viral vectors as the transfection vectors of choice [17][18][19][20][21][22]. Commercially available transfection reagents (cationic lipid and polyamine based) have been reported for transfecting plasmid DNA in RAW 264.7 cells.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

“…All the above-mentioned alarming limitations for using viral vectors are increasingly making non-viral gene carriers as the transfection vectors of choice for delivering genes into cells [17]. Cationic polymers [18], cationic lipids [19,20], cationic dendrimers [21], cationic peptides [22], etc are being used as non-viral transfection vectors. Among these nonviral gene carriers, cationic liposomes and lipid-based nanoparticles are finding more pre-clinical and clinical uses because of their lower immunogenicity, targetability and lack of insert size limits [19,20,23].…”

Section: Introductionmentioning

confidence: 99%

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RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

Rahaman,

Chaudhuri

2023

Biomed. Mater.

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To ensure effective immune response in genetic immunizations, DNA/mRNA vaccines need to be delivered to body’s antigen presenting cells (APCs) which is a challenging task. This is primarily due to presence of high concentrations of various degradative enzymes inside them. To this end, mannose receptor (over expressed in APCs) selective cationic liposomes have been used in the past for delivering antigen-encoded plasmid DNA to APCs. APCs also express integrin receptors on their cell surfaces. However, studies aimed at delivering DNA vaccines into APCs via integrin receptors have not yet been undertaken. Herein, we report on the use of cationic liposomes of a priorly disclosed α5β1 integrin receptor selective RGDK-lipopeptide for macrophage transfection. In this study, we have used pCMV-GFP (as model DNA vaccine) and RAW 264.7 cells (mouse macrophages cells) as model APC. We show that the liposomes of RGDK-lipopeptide containing a previously reported endosome-disrupting histidinylated lipid and DOPE (as co-lipid) in 0.5:0.5:1.0 mole ratio are the most competent in transfecting macrophage cells (44%). Findings in the fluorescence resonance energy transfer based membrane fusogencity assay revealed that the enhanced macrophage transfection efficiency of the liposomes containing RGDK-lipopeptide, endosome-disrupting histidinylated and DOPE may originate from its higher membrane fusogenicity than that for liposomes containing only RGDK-lipopeptide and DOPE. The presently described biologically safe liposomal formulations of RGDK-lipopeptide are expected to find biomedical applications in future for combating cancer and infectious diseases through genetic immunizations.

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Section: Cytotoxicity Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

Rahaman,

Chaudhuri

2023

Biomed. Mater.

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“…The positively‐charged surface may facilitate cellular uptake due to the electrostatic interaction with the cell surface. [ 14 ] While no considerable difference in DLS measurements was observed between the two cationic sequences, mitoNEET‐(RH) 9 and mitoNEET‐(KH) 9 , the circular dichroism (CD) measurements showed an interesting difference ( Figure a,b). In mitoNEET‐(RH) 9 polyplexes prepared at an N/P ratio of 2, 78% of the peptides formed an α‐helical structure.…”

Section: Resultsmentioning

confidence: 99%

Design of an Artificial Peptide Inspired by Transmembrane Mitochondrial Protein for Escorting Exogenous DNA into the Mitochondria to Restore their Functions by Simultaneous Multiple Gene Expression

Yoshinaga,

Miyamoto,

Odahara

et al. 2023

Adv Funct Materials

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Mitochondria are vital organelles regulating essential cellular functions. Human mitochondrial DNA (mtDNA) consists of 37 genes, 13 of which encode mitochondrial proteins, and the remaining 24 genes encode two ribosomal RNAs and 22 transfer RNAs needed for the translation of the mtDNA‐encoded 13 proteins. However, mtDNA often impairs the expression and function of these genes due to various mutations, ultimately causing mitochondrial dysfunction. To recover from this desperate condition, developing the technology to supply all mitochondrial proteins encoded by mtDNA at once is an urgent task, but there is no established strategy for this purpose. In this study, a simple yet effective mitochondrial gene delivery system is proposed comprising an artificial peptide inspired by a transmembrane mitochondrial membrane protein. The designed mitochondria‐targeting peptides presented on the carrier surface effectively guide the encapsulated plasmid to the mitochondria, facilitating mitochondrial uptake and gene expression. The developed system successfully delivers exogenous mtDNA to mtDNA‐depleted cells and leads to simultaneous multigene expression, ultimately restoring mitochondrial functions, including the mitochondrial respiration rate. The established multiple gene expression system in each mitochondrion is a game‐changing technology that can accelerate the development of mitochondrial engineering technologies as well as clinical applications for mitochondrial diseases.

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“…Although different groups are seeking an effective vaccine against HTLV-1, to date, there remains no efficient vaccine for HTLV-1 infection [ 30 ]. Peptide-based vaccines have vital benefits such as safety, lower expenses, and high efficiency [ 31 ]. However, creating a reliable peptide vaccine has difficulties, such as the reduced innate immunogenicity of each epitope [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice

et al. 2023

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The human T-cell leukemia virus type 1 (HTLV-1) is a positive single-stranded RNA virus that belongs to the delta retrovirus family. As a result, a vaccine candidate that can be recognized by B cells and T cells is a good candidate for generating a durable immune response. Further, the GPEHT protein is a multi-epitope protein designed based on the Gag, Pol, Env, Hbz, and Tax proteins of HTLV-1. In developing a suitable and effective vaccine against HTLV-1, the selection of a designed protein (GPEHT) with the formulation of an alum adjuvant was conducted. In this study, we assessed the potential of a multi-epitope vaccine candidate for stimulating the immune response against HTLV-1. In assessing the type of stimulated immune reaction, total IgG, IgG1, and IgG2a isotypes, as well as the cytokines associated with Th1 (IFN-γ), Th2 (IL-4), and Th17 (IL-17), were analyzed. The outcomes showed that the particular antisera (total IgG) were more elevated in mice that received the GPEHT protein with the alum adjuvant than those in the PBS+Alum control. A subcutaneous vaccination with our chimera protein promoted high levels of IgG1 and IgG2a isotypes. Additionally, IFN-γ, IL-4, and IL-17 levels were significantly increased after spleen cell stimulation in mice that received the GPEHT protein. The immunogenic analyses revealed that the GPEHT vaccine candidate could generate humoral and cell-mediated immune reactions. Ultimately, this study suggests that GPEHT proteins developed with an alum adjuvant can soon be considered as a prospective vaccine to more accurately evaluate their protective efficacy against HTLV-1.

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Peptide-based DNA delivery system

Cited by 9 publications

References 40 publications

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

Design of an Artificial Peptide Inspired by Transmembrane Mitochondrial Protein for Escorting Exogenous DNA into the Mitochondria to Restore their Functions by Simultaneous Multiple Gene Expression

Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice

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