Erythrocyte‐mediated delivery of recombinant enzymes

Leuzzi, Vincenzo; Rossi, Luigia; Gabucci, Claudia; Nardecchia, Francesca; Magnani, Mauro

doi:10.1007/s10545-016-9926-0

Cited by 19 publications

(19 citation statements)

References 85 publications

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“…Rubius has also announced a strong pipeline with some preclinical data published. Of interest, due to space limitation, we will address readers to several reviews that have summarized the potential clinical developments of several different candidates already tested in suitable animal models [44][45][46][47][48]. The envisaged applications cover many different areas including delivery of small chemical entities, therapeutic proteins, enzymes, immune modulators, and contrasting agents for diagnostic applications.…”

Section: Preclinical Pipelinementioning

confidence: 99%

Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

et al. 2020

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Engineered red blood cells (RBCs) appear to be a promising method for therapeutic drug and protein delivery. With a number of agents in clinical trials (e.g., dexamethasone 21-phosphate in ataxia telangiectasia, asparaginase in pancreatic cancer/acute lymphoblastic leukemia, thymidine phosphorylase in mitochondrial neurogastrointestinal encephalomyopathy, RTX-134 in phenylketonuria, etc.), this leading article summarizes the ongoing efforts in developing these agents, focuses on the clinical progress, and provides a brief background into engineered RBCs and the different ways in which they can be exploited for therapeutic/diagnostic purposes. References to available data on safety, efficacy, and tolerability are reported. Due to the continuous progress in this field, the information is updated as of January 2020 from databases, websites, and press releases of the involved companies and information that is in the public domain.

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Section: Preclinical Pipelinementioning

confidence: 99%

Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

et al. 2020

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“…These achievements (summarized in the next sections) are possible only thanks to the exclusive features of these cells which allow them to be engineered without altering their properties or compromising their in vivo circulation. In fact, the biochemical characteristics of RBC, their physiology as well as the molecular mechanisms governing the natural fate of the senescent or damaged cells, make them attractive candidates as carriers of conventional and/or new drugs, as extensively documented in recent, excellent, reviews . RBC are among the most abundant cell types in a human body: they comprise approximately one quarter of the total cell number and are the main component of blood with the crucial role of carriers of oxygen and carbon dioxide.…”

Section: Biology and Circulation Of Human Rbcmentioning

confidence: 99%

“…Different RBC species have the potential as delivery vehicle of therapeutic and/or diagnostic compounds in preclinical studies when the development of feasibility, iterative testing and safety data need to be collected before first‐in‐man study and clinical trials. Two main methodologies have been developed to yield processed RBC, the drug attachment on their surface or the entrapment of exogenous or endogenous agents within them, as extensively reported in literature . In the latter case, the processing of drug encapsulation requires a reversible and transient permeability change in the erythrocyte membrane, which can be achieved by various physical or chemical means.…”

Section: Erythrocytes From Different Animal Species and Preclinical Smentioning

confidence: 99%

Reengineering red blood cells for cellular therapeutics and diagnostics

Pierigé

Bigini

Rossi

et al. 2017

WIREs Nanomed Nanobiotechnol

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Recently optimized technologies that permit the reversible opening of nanopores across the red blood cell membrane, give the extraordinary opportunity for reengineering human erythrocytes to be used in different biomedical applications, both for therapeutic and diagnostic purposes. Engineered erythrocytes have been exploited as a system for the controlled release of drugs in circulation upon encapsulation of prodrugs or small molecules; as bioreactors when they are endowed of recombinant enzymes able to catalyze the conversion of toxic metabolite into inert products; as drug targeting system for the delivery of compounds to the reticuloendothelial system inducing proper senescent signals on the drug-loaded erythrocyte membrane; as carrier of contrasting agents for diagnostic procedures. Preclinical development of these different applications has taken advantage from the use of proper animal models whose erythrocytes can be reengineered as the human ones or the encapsulation procedures can be adapted on the basis of their specific erythrocyte biological features. Successful results, obtained both in vitro and in preclinical studies, have prompted several clinicians to start pilot clinical investigations in different conditions and some new companies to start the industrialization of selected loading technologies and to initiate clinical development programs. This short review summarizes the key features that, to the best of our knowledge, have been crucial to advance the products toward regulatory clinical approval making reengineering of erythrocytes a modality to treat patients with limited or absent therapeutic options. WIREs Nanomed Nanobiotechnol 2017, 9:e1454. doi: 10.1002/wnan.1454 For further resources related to this article, please visit the WIREs website.

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“…10 Furthermore, intentional usage of human and animal erythrocytes, erythrocyte membranes (i.e., ghosts), and their nanoderivatives presents modern approach in terms of prolonged and controlled drug delivery systems. [11][12][13][14] Recently, we have reported the production of drug encapsulated porcine and bovine erythrocyte ghosts by gradual hypotonic hemolysis in much higher quantities than those described in literature so far. 13 However, it was noted that after the hemolysis process a certain amount of hemoglobin remains in the final suspension of the resulting erythrocyte ghosts.…”

Section: Introductionmentioning

confidence: 98%

Mapping of hemoglobin in erythrocytes and erythrocyte ghosts using two photon excitation fluorescence microscopy

et al. 2017

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The present study describes utilization of two photon excitation fluorescence (2PE) microscopy for visualization of the hemoglobin in human and porcine erythrocytes and their empty membranes (i.e., ghosts). High-quality, label- and fixation-free visualization of hemoglobin was achieved at excitation wavelength 730 nm by detecting visible autofluorescence. Localization in the suspension and spatial distribution (i.e., mapping) of residual hemoglobin in erythrocyte ghosts has been resolved by 2PE. Prior to the 2PE mapping, the presence of residual hemoglobin in the bulk suspension of erythrocyte ghosts was confirmed by cyanmethemoglobin assay. 2PE analysis revealed that the distribution of hemoglobin in intact erythrocytes follows the cells’ shape. Two types of erythrocytes, human and porcine, characterized with discocyte and echinocyte morphology, respectively, showed significant differences in hemoglobin distribution. The 2PE images have revealed that despite an extensive washing out procedure after gradual hypotonic hemolysis, a certain amount of hemoglobin localized on the intracellular side always remains bound to the membrane and cannot be eliminated. The obtained results open the possibility to use 2PE microscopy to examine hemoglobin distribution in erythrocytes and estimate the purity level of erythrocyte ghosts in biotechnological processes.

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Erythrocyte‐mediated delivery of recombinant enzymes

Cited by 19 publications

References 85 publications

Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

Reengineering red blood cells for cellular therapeutics and diagnostics

Mapping of hemoglobin in erythrocytes and erythrocyte ghosts using two photon excitation fluorescence microscopy

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