Asn194Lys mutation in RVG29 peptide increases GFP transgene delivery by endocytosis to neuroblastoma and astrocyte cells

Villa‐Cedillo, Sheila Adela; Rodríguez-Rocha, Humberto; Zavala-Flores, Laura; Montes‐de‐Oca‐Luna, Roberto; García-García, Aracely; Loera‐Arias, María de Jesús; Saucedo‐Cárdenas, Odila

doi:10.1111/jphp.12766

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…Although the delivery of RNA molecules to the brain with RVG‐9R has already been described (Kumar et al, ), in this study we proved that the modification of an amino acid (mRVG‐9R) is more efficient in the delivery of charge molecules than the RVG‐9R peptide as we published previously (Villa‐Cedillo et al, ). And now we have demonstrated its transfection capacity in vivo.…”

Section: Discussionsupporting

confidence: 83%

“…In our previous report, we confirmed successful cellular transfection of neuroblastoma cells and astrocytes i n vitro using mRVG‐9R complexes (Villa‐Cedillo et al, ).…”

Section: Resultssupporting

confidence: 76%

“…Our research group has developed a peptide‐based delivery system that includes the Asn194Lys mutation in the RVG‐9R peptide (mRVG‐9R). This system has proven to have high efficiency in the delivery of DNA as cargo molecule to neuronal phenotype cells and astrocytes in vitro, but is not able to transfect oligodendrocyte precursor cells (OPCs) (Villa‐Cedillo et al, ).…”

Section: Introductionmentioning

confidence: 99%

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The mRVG‐9R peptide as a potential therapeutic vector to the central nervous system cells

Villa‐Cedillo

Soto‐Domínguez

Rodríguez-Rocha

et al. 2019

Cell Biology International

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Our research group has developed a cell‐penetrating peptide‐based delivery system that includes the Asn194Lys mutation in the rabies virus glycoprotein‐9R peptide (mRVG‐9R). This system has the capacity to deliver DNA in astrocytes and SH‐SY5Y cells. The aim of this study was to evaluate the ability of the mRVG‐9R peptide to deliver DNA molecules to murine brain cells. The mRVG‐9R peptide, a karyophilic peptide (KP) and a plasmid encoding green fluorescent protein (GFP) were bound by electrostatic charges to form the mRVG‐9R complex. mRVG‐9R complex was injected into the cerebral cortex, striatum and hippocampus of C57BL/6 mice by stereotactic surgery. After 2, 4, and 20 days, the animals were sacrificed and their brains were prepared for quantitative reverse‐transcription polymerase chain reaction and histological analysis. We detected the GFP expression in neurons and glial cells in the cerebral cortex, striatum, and hippocampus of the murine brain. The results suggest that the mRVG‐9R peptide has the ability to deliver DNA molecules to murine brain cells. Also, the expression of the reporter gene is maintained at least up to 20 days after injection in neurons, astrocytes, oligodendrocytes, and microglia cells. Thus, the in vivo transfection ability of the mRVG‐9R peptide, makes it a promising candidate as a therapeutic gene delivery vector to the central nervous system cells.

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Section: Discussionsupporting

confidence: 83%

“…In our previous report, we confirmed successful cellular transfection of neuroblastoma cells and astrocytes i n vitro using mRVG‐9R complexes (Villa‐Cedillo et al, ).…”

Section: Resultssupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The mRVG‐9R peptide as a potential therapeutic vector to the central nervous system cells

Villa‐Cedillo

Soto‐Domínguez

Rodríguez-Rocha

et al. 2019

Cell Biology International

Self Cite

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“…Interestingly, we showed that a peptide, composed of the BH4 domain of the anti-apoptotic Bcl-xL protein fused to the protein transduction domain of the HIV-1 TAT protein, was able to cross the BBB and protect astrocytes in vivo in a mouse model of ALS, after systemic administration [85]. Although lacking specificity towards astrocytes, this approach resulted promising and highlighted features of the delivery system that are shared by other peptides derived from different viral glycoproteins [193,203,204]. More recently, a homing peptide, named AS1 and showing high affinity and specificity for the astrocytes, was discovered during a phage display study [205].…”

Section: Peptide-based Deliverymentioning

confidence: 99%

Challenges and Opportunities of Targeting Astrocytes to Halt Neurodegenerative Disorders

Valori

Possenti

Brambilla

et al. 2021

Cells

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Neurodegenerative diseases are a heterogeneous group of disorders whose incidence is likely to duplicate in the next 30 years along with the progressive aging of the western population. Non-cell-specific therapeutics or therapeutics designed to tackle aberrant pathways within neurons failed to slow down or halt neurodegeneration. Yet, in the last few years, our knowledge of the importance of glial cells to maintain the central nervous system homeostasis in health conditions has increased exponentially, along with our awareness of their fundamental and multifaced role in pathological conditions. Among glial cells, astrocytes emerge as promising therapeutic targets in various neurodegenerative disorders. In this review, we present the latest evidence showing the astonishing level of specialization that astrocytes display to fulfill the demands of their neuronal partners as well as their plasticity upon injury. Then, we discuss the controversies that fuel the current debate on these cells. We tackle evidence of a potential beneficial effect of cell therapy, achieved by transplanting astrocytes or their precursors. Afterwards, we introduce the different strategies proposed to modulate astrocyte functions in neurodegeneration, ranging from lifestyle changes to environmental cues. Finally, we discuss the challenges and the recent advancements to develop astrocyte-specific delivery systems.

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“…RVG peptide containing nine arginine residues to the carboxy terminus was reported as a useful siRNA carrier to the brain across the BBB via systemic administration, and the combination of RVG peptide with various carriers for drug and gene delivery to the CNS was further reported [ 32 , 33 , 34 , 35 ]. However, perhaps because of the difference in molecule size, polyplexes of RVG peptide and pDNA have not been well reported without modifications for condensation or stability of polyplexes [ 36 , 37 , 38 ]. In this study, a ternary complex was prepared using PEGylated polyethyleneimine (PEG-PEI) to improve the in vivo stability of the polyplex.…”

Section: Introductionmentioning

confidence: 99%

Ternary Complexes of pDNA, Neuron-Binding Peptide, and PEGylated Polyethyleneimine for Brain Delivery with Nano-Bubbles and Ultrasound

et al. 2021

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In brain-targeted delivery, the transport of drugs or genes across the blood−brain barrier (BBB) is a major obstacle. Recent reports found that focused ultrasound (FUS) with microbubbles enables transient BBB opening and improvement of drug or gene delivery. We previously developed nano-sized bubbles (NBs), which were prepared based on polyethylene glycol (PEG)-modified liposomes containing echo-contrast gas, and showed that our NBs with FUS could also induce BBB opening. The aim of this study was to enhance the efficiency of delivery of pDNA into neuronal cells following transportation across the BBB using neuron-binding peptides. This study used the RVG-R9 peptide, which is a chimeric peptide synthesized by peptides derived from rabies virus glycoprotein and nonamer arginine residues. The RVG peptide is known to interact specifically with the nicotinic acetylcholine receptor in neuronal cells. To enhance the stability of the RVG-R9/pDNA complex in vivo, PEGylated polyethyleneimine (PEG-PEI) was also used. The ternary complexes composed of RVG-R9, PEG-PEI, and pDNA could interact with mouse neuroblastoma cells and deliver pDNA into the cells. Furthermore, for the in vivo experiments using NBs and FUS, gene expression was observed in the FUS-exposed brain hemispheres. These results suggest that this systemic gene delivery system could be useful for gene delivery across the BBB.

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Asn194Lys mutation in RVG29 peptide increases GFP transgene delivery by endocytosis to neuroblastoma and astrocyte cells

Abstract: The complexes pGL-mRVG29 and pGL-RVG29-KP have specificity for transfecting astrocytes and SH-SY5Y cells. The karyophilic capacity of this new mRVG peptide render it promising candidate to act as gene delivery vector into the brain cells.

Cited by 10 publications

References 35 publications

The mRVG‐9R peptide as a potential therapeutic vector to the central nervous system cells

The mRVG‐9R peptide as a potential therapeutic vector to the central nervous system cells

Challenges and Opportunities of Targeting Astrocytes to Halt Neurodegenerative Disorders

Ternary Complexes of pDNA, Neuron-Binding Peptide, and PEGylated Polyethyleneimine for Brain Delivery with Nano-Bubbles and Ultrasound

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