RNA Therapeutics: How Far Have We Gone?

Coutinho, Maria Francisca; Matos, Liliana; Santos, Juliana Inês; Alves, Sandra

doi:10.1007/978-3-030-19966-1_7

Cited by 39 publications

(44 citation statements)

References 289 publications

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“…Pharmaceutics 2020, 12,198 9 of 29 surface avoids endocytosis by the reticuloendothelial system (RES), and it therefore increases the halflive period of such niosomes in blood [92].…”

Section: Niosome Preparation Methodsmentioning

confidence: 99%

“…Another relevant issue that needs to be considered is the natural tendency to accumulate in the liver after intravenous administration, and the fact that such biomacromolecules, due to their small size, below 5.5 nm, can be cleared quickly from systemic circulation through kidneys by renal excretion [30]. In any case, although genetic material remains stable in bloodstream without eliciting an immune response, the time required to reach therapeutic concentrations-the transfection process-can be even more challenging if isolated and immune-privileged organs such as brain and eye are the final Pharmaceutics 2020, 12,198 5 of 29 target of the gene therapy treatment. In this case, additional extracellular barriers that protect the brain and eye from the rest of the organism such as the blood-brain barrier (BBB) and the blood-retinal barrier (BRB) need to be overcome [31,32].…”

Section: Extracellular Barriersmentioning

confidence: 99%

“…Pharmaceutics 2020, 12,198 5 of 29 delivery systems for in vivo gene therapy represents a really stimulating task for the scientific community. A schematic representation of extracellular barriers is shown in Figure 1.…”

Section: Extracellular Barriersmentioning

confidence: 99%

“…Pharmaceutics 2020, 12,198 13 of 29 an overview of the gene delivery efficiency of niosomes, further readjustments on cationic lipid/genetic material ratio need to be performed when moving to therapeutic plasmids, since both the composition and size of the plasmid directly influence the transfection efficiency process [113]. The knowledge of the endocytosis pathway and the posterior intracellular trafficking to reach the nucleus of target cells can be useful to design more efficient and safer niosome vesicles for gene delivery applications [51].…”

Section: In Vitro Biological Evaluation Of Niosomes For Gene Deliverymentioning

confidence: 99%

“…Pharmaceutics 2020, 12,198 19 of 29 evaporation technique and characterized to deliver the genetic material into the rat brain cortex. When poloxamer 188 was incorporated into the niosomes, the sizes of niosomes increased, which was probably due to the high HLB value of poloxamer 188 and to the interaction with the cationic lipid [161].…”

Section: Niosomes For Gene Delivery To the Brainmentioning

confidence: 99%

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Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

et al. 2020

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Non-viral vectors have emerged as a promising alternative to viral gene delivery systems due to their safer profile. Among non-viral vectors, recently, niosomes have shown favorable properties for gene delivery, including low toxicity, high stability, and easy production. The three main components of niosome formulations include a cationic lipid that is responsible for the electrostatic interactions with the negatively charged genetic material, a non-ionic surfactant that enhances the long-term stability of the niosome, and a helper component that can be added to improve its physicochemical properties and biological performance. This review is aimed at providing recent information about niosome-based non-viral vectors for gene delivery purposes. Specially, we will discuss the composition, preparation methods, physicochemical properties, and biological evaluation of niosomes and corresponding nioplexes that result from the addition of the genetic material onto their cationic surface. Next, we will focus on the in situ application of such niosomes to deliver the genetic material into immune-privileged tissues such as the brain cortex and the retina. Finally, as future perspectives, non-invasive administration routes and different targeting strategies will be discussed.

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“…Pharmaceutics 2020, 12,198 9 of 29 surface avoids endocytosis by the reticuloendothelial system (RES), and it therefore increases the halflive period of such niosomes in blood [92].…”

Section: Niosome Preparation Methodsmentioning

confidence: 99%

Section: Extracellular Barriersmentioning

confidence: 99%

Section: Extracellular Barriersmentioning

confidence: 99%

Section: In Vitro Biological Evaluation Of Niosomes For Gene Deliverymentioning

confidence: 99%

Section: Niosomes For Gene Delivery To the Brainmentioning

confidence: 99%

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Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

et al. 2020

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Splicing factor arginine/serine‐rich 8 promotes multiple myeloma malignancy and bone lesion through alternative splicing of CACYBP and exosome‐based cellular communication

Zhang

Sun

et al. 2022

Clinical & Translational Med

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Background Multiple myeloma (MM) is a distinctive malignancy of plasma cell within the bone marrow (BM), of which alternative splicing factors play vital roles in the progression. Splicing factor arginine/serine‐rich 8 (SFRS8) is the exclusive factor associated with MM prognosis, however its role in MM remains undefined. Methods The analyses of 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide (MTT) assay, immunohistochemistry, flow cytometry and xenograft model were performed to examine cell proliferation, cell cycle and apoptosis in SFRS8 overexpression or knockdown MM cells in vitro and in vivo. The SFRS8‐regulated alternative splicing events were identified by RNA immunoprecipitation sequencing (RIP‐seq) and validated by RIP‐qPCR and Co‐IP methods. Exosomes were extracted from the supernatant of myeloma cells by ultracentrifugation. Bone lesion was evaluated by TRAP staining in vitro and SCID/NOD‐TIBIA mouse model. A neon electroporation system was utilised to deliver siRNA through exosomes. The effect of siRNA‐loaded exosomes in vivo was evaluated by using a patient‐derived tumor xenograft (PDX) model and SCID/NOD‐TIBIA mouse model. Results SFRS8 was significantly upregulated in MM samples and positively associated with poor overall survival (OS) in MM patients. SFRS8 promoted MM cell proliferation in vitro and in vivo. Furthermore, calcyclin binding protein (CACYBP) was identified as the downstream target of SFRS8. Particularly, SFRS8 could reduce CACYBP isoform1 (NM_014412.3) and increase CACYBP isoform2 (NM_001007214.1) by mediating the alternative splicing of CACYBP, thereby altering the ubiquitination degradation of β‐catenin to promote MM progression. In addition, SFRS8 promoted osteoclast differentiation through exosomes in vitro and in vivo. More importantly, exosomal siRNA targeting CACYBP isoform2 inhibited tumour growth in PDX and SCID/NOD‐TIBIA mouse models. Conclusion Our findings demonstrate that targeting the SFRS8/CACYBP/β‐catenin axis may be a promising strategy for MM diagnosis and treatment.

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The current perspective and opportunities of small nucleic acid‐based therapeutics

Chen,

Li,

et al. 2024

Drug Development Research

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Compared to traditional small molecule and antibody drugs, RNA‐based drugs offer a simple design, short research and development cycles, high specificity, broad treatment fields, and long‐term efficacy. As a result, RNA‐based drugs are extensively used to treat genetic diseases, tumors, viral infections, and other illnesses, suggesting that they have the potential to become the third‐largest drug class after small molecule and antibody drugs. Currently, more than 10 small nucleic acid drugs have gained regulatory approval. The commercialization successes of small nucleic acid drugs will stimulate the development of RNA‐based drugs. Small nucleic acid drugs primarily target liver diseases, metabolic diseases, genetic diseases, and tumors, and there is also significant potential for expanding indications in the future. This review provides a brief overview of the advantages and development of small nucleic acid‐based therapeutics and shows a focus on platform technologies such as chemical modifications and delivery systems that have enabled the clinical translation of small nucleic acid‐based therapeutics. Additionally, we summarize the latest clinical progress in small nucleic acid‐based therapeutics for the treatment of various diseases, including rare diseases, liver diseases, metabolic diseases, and tumors. Finally, we highlight the future prospects for this promising treatment approach.

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RNA Therapeutics: How Far Have We Gone?

Cited by 39 publications

References 289 publications

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

Splicing factor arginine/serine‐rich 8 promotes multiple myeloma malignancy and bone lesion through alternative splicing of CACYBP and exosome‐based cellular communication

The current perspective and opportunities of small nucleic acid‐based therapeutics

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