scholarly journals Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 364 ◽  
Author(s):  
Itziar Gómez-Aguado ◽  
Julen Rodríguez-Castejón ◽  
Mónica Vicente-Pascual ◽  
Alicia Rodríguez-Gascón ◽  
María Ángeles Solinís ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plasmid Dna ◽  
Messenger Rna ◽  
Insertional Mutagenesis ◽  
Gene Editing ◽  
State Of The Art ◽  
Translational Efficiency ◽  
Future Perspectives ◽  
Therapeutic Tool

The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.

scholarly journals Clinical and immunological effects of mRNA vaccines in malignant diseases

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Annkristin Heine ◽  
Stefan Juranek ◽  
Peter Brossart
Keyword(s):  
Immune Responses ◽  
Messenger Rna ◽  
Immune Escape ◽  
Special Focus ◽  
Potential Efficacy ◽  
Protective Antibodies ◽  
Technological Developments ◽  
Broad Variety ◽  
Antigen Loss

AbstractIn vitro-transcribed messenger RNA-based therapeutics represent a relatively novel and highly efficient class of drugs. Several recently published studies emphasize the potential efficacy of mRNA vaccines in treating different types of malignant and infectious diseases where conventional vaccine strategies and platforms fail to elicit protective immune responses. mRNA vaccines have lately raised high interest as potent vaccines against SARS-CoV2. Direct application of mRNA or its electroporation into dendritic cells was shown to induce polyclonal CD4+ and CD8+ mediated antigen-specific T cell responses as well as the production of protective antibodies with the ability to eliminate transformed or infected cells. More importantly, the vaccine composition may include two or more mRNAs coding for different proteins or long peptides. This enables the induction of polyclonal immune responses against a broad variety of epitopes within the encoded antigens that are presented on various MHC complexes, thus avoiding the restriction to a certain HLA molecule or possible immune escape due to antigen-loss. The development and design of mRNA therapies was recently boosted by several critical innovations including the development of technologies for the production and delivery of high quality and stable mRNA. Several technical obstacles such as stability, delivery and immunogenicity were addressed in the past and gradually solved in the recent years.This review will summarize the most recent technological developments and application of mRNA vaccines in clinical trials and discusses the results, challenges and future directions with a special focus on the induced innate and adaptive immune responses.

scholarly journals CRISPR-Directed In Vitro Gene Editing of Plasmid DNA Catalyzed by Cpf1 (Cas12a) Nuclease and a Mammalian Cell-Free Extract

2018 ◽  
Vol 1 (2) ◽  
pp. 191-202 ◽  
Author(s):  
Brett M. Sansbury ◽  
Amanda M. Wagner ◽  
Erez Nitzan ◽  
Gabi Tarcic ◽  
Eric B. Kmiec
Keyword(s):  
Mammalian Cell ◽  
Plasmid Dna ◽  
Gene Editing ◽  
Cell Free Extract

Female fertility preservation strategies: cryopreservation and ovarian tissuein vitroculture, current state of the art and future perspectives

Zygote ◽  
2016 ◽  
Vol 24 (5) ◽  
pp. 635-653 ◽  
Author(s):  
M.A. Filatov ◽  
Y.V. Khramova ◽  
M.V. Kiseleva ◽  
I.V. Malinova ◽  
E.V. Komarova ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
State Of The Art ◽  
Ovarian Tissue ◽  
Female Fertility ◽  
Ovarian Tissue Cryopreservation ◽  
Future Perspectives ◽  
Current State ◽  
Female Fertility Preservation ◽  
Tissue Cryopreservation

SummaryIn the present review, the main strategies of female fertility preservation are covered. Procedures of fertility preservation are necessary for women who suffer from diseases whose treatment requires the use of aggressive therapies, such as chemotherapy and radiotherapy. These kinds of therapy negatively influence the health of gametes and their progenitors. The most commonly used method of female fertility preservation is ovarian tissue cryopreservation, followed by the retransplantation of thawed tissue. Another approach to female fertility preservation that has been actively developed lately is the ovarian tissuein vitroculture. The principal methods, advantages and drawbacks of these two strategies are discussed in this article.

scholarly journals RNA-Based Vaccines in Cancer Immunotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Megan A. McNamara ◽  
Smita K. Nair ◽  
Eda K. Holl
Keyword(s):  
Immune Response ◽  
Cancer Immunotherapy ◽  
Rna Structure ◽  
Messenger Rna ◽  
Host Cells ◽  
Translational Efficiency ◽  
Tumor Associated Antigen ◽  
Antigen Presenting ◽  
Template Dna

RNA vaccines traditionally consist of messenger RNA synthesized byin vitrotranscription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

scholarly journals 3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives

2022 ◽  
Author(s):  
Yi Xiang ◽  
Kathleen Miller ◽  
Jiaao Guan ◽  
Wisarut Kiratitanaporn ◽  
Min Tang ◽  
...  
Keyword(s):  
State Of The Art ◽  
In Vitro Models ◽  
Future Perspectives ◽  
Precise Control ◽  
Broad Variety ◽  
3D Printed ◽  
Pharmacology And Toxicology ◽  
Increasing Demand ◽  
Tissue Models

AbstractThe pharmacology and toxicology of a broad variety of therapies and chemicals have significantly improved with the aid of the increasing in vitro models of complex human tissues. Offering versatile and precise control over the cell population, extracellular matrix (ECM) deposition, dynamic microenvironment, and sophisticated microarchitecture, which is desired for the in vitro modeling of complex tissues, 3D bio-printing is a rapidly growing technology to be employed in the field. In this review, we will discuss the recent advancement of printing techniques and bio-ink sources, which have been spurred on by the increasing demand for modeling tactics and have facilitated the development of the refined tissue models as well as the modeling strategies, followed by a state-of-the-art update on the specialized work on cancer, heart, muscle and liver. In the end, the toxicological modeling strategies, substantial challenges, and future perspectives for 3D printed tissue models were explored.

scholarly journals SPECIFIC PROTEIN SYNTHESIS IN CELLULAR DIFFERENTIATION

1972 ◽  
Vol 55 (3) ◽  
pp. 653-680 ◽  
Author(s):  
M. Paul ◽  
M. R. Goldsmith ◽  
J. R. Hunsley ◽  
F. C. Kafatos
Keyword(s):  
Protein Synthesis ◽  
Messenger Rna ◽  
Developmental Stages ◽  
Specific Protein ◽  
Chain Elongation ◽  
Synthetic Activity ◽  
Translational Efficiency ◽  
Kinetics Of

Silkmoth follicles, arranged in a precise developmental sequence within the ovariole, yield pure and uniform populations of follicular epithelial cells highly differentiated for synthesis of the proteinaceous eggshell (chorion). These cells can be maintained and labeled efficiently in organ culture; their in vitro (and cell free) protein synthetic activity reflects their activity in vivo. During differentiation the cells undergo dramatic changes in protein synthesis. For 2 days the cells are devoted almost exclusively to production of distinctive chorion proteins of low molecular weight and of unusual amino acid composition. Each protein has its own characteristic developmental kinetics of synthesis. Each is synthesized as a separate polypeptide, apparently on monocistronic messenger RNA (mRNA), and thus reflects the expression of a distinct gene. The rapid changes in this tissue do not result from corresponding changes in translational efficiency. Thus, the peptide chain elongation rate is comparable for chorion and for proteins synthesized at earlier developmental stages (1.3–1.9 amino acids/sec); moreover, the spacing of ribosomes on chorion mRNA (30–37 codons per ribosome) is similar to that encountered in other eukaryotic systems.

scholarly journals SEMAPHORIN 3A - A NEW INTRATHYMIC SUPPRESSOR FACTOR

2019 ◽  
Vol 19 (1S) ◽  
pp. 203-205
Author(s):  
K V Rutto ◽  
E P Kisseleva
Keyword(s):  
Immune Responses ◽  
Axon Guidance ◽  
Cell Activity ◽  
Thymic Epithelial Cells ◽  
Neuronal System ◽  
Semaphorin 3A ◽  
Therapeutic Tool ◽  
Suppressor Factor ◽  
Immunosuppressive Factor

Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several semaphorins, so-called ‘immune semaphorins’, are also involved in various phases of immune responses. One of such factors is semaphorin 3A - a member of class 3 semaphorins, which are secretory molecules in vertebrates. There are multiple mechanisms involved in the process of semaphorin 3A-mediated regulation. One of them is down-regulation of peripheral T-cell activity in consequence of which semaphorin 3A is considered as an immunosuppressive factor. But semaphorin 3A is also expressed in the thymus while its function there remains obscure. Here are discussed new data on immunosuppressive function of this factor towards thymocytes and thymic epithelial cells, obtained in vitro. Because it is involved both in physiological immunoregulation and in the pathogenesis of many autoimmune, atopic, and malignant diseases, semaphorin 3A turns to be a promising therapeutic tool to be studied and applied in these diseases.

scholarly journals Silencing of the Mutant Huntingtin Gene through CRISPR-Cas9 Improves the Mitochondrial Biomarkers in an In Vitro Model of Huntington’s Disease

2019 ◽  
Vol 28 (4) ◽  
pp. 460-463 ◽  
Author(s):  
Gary L. Dunbar ◽  
Sindhuja Koneru ◽  
Nivya Kolli ◽  
Michael Sandstrom ◽  
Panchanan Maiti ◽  
...  
Keyword(s):  
Gene Editing ◽  
In Vitro Model ◽  
Mutant Huntingtin ◽  
Therapeutic Tool ◽  
Neural Therapy ◽  
Viral Genes ◽  
History Of ◽  
Vitro Model ◽  
American Society

During the 25-year history of the American Society for Neural Therapy and Repair (ASNTR) there have been several breakthroughs in the area of neurotherapeutics, which was the case during the 2014–2105 year when one of us (GLD) had the privilege of serving as its president. During that year, the use of a newly developed gene-editing tool, the CRISPR-Cas9 system, started to skyrocket. Although scientists unraveled the use of “clustered regularly interspaced short palindromic repeats” (CRISPR) and its associated genes from the Cas family as an evolved mechanism of some bacterial and archaeal genomes to protect themselves from being hijacked by invasive viral genes, its use as a therapeutic tool was not fully appreciated until further research revealed how this system operated and how it might be developed technologically to manipulate genes of any species. By 2015, this technology had exploded to the point that close to 2,000 papers that used this technology were published during that year alone.

scholarly journals A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5′–3′ messenger RNA decay

2019 ◽  
Vol 47 (17) ◽  
pp. 9282-9295 ◽  
Author(s):  
Chung-Te Chang ◽  
Sowndarya Muthukumar ◽  
Ramona Weber ◽  
Yevgen Levdansky ◽  
Ying Chen ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Low Complexity ◽  
Ribosome Profiling ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Translational Efficiency ◽  
Mrna Levels ◽  
Null Cell ◽  
Integrated Network

Abstract XRN1 is the major cytoplasmic exoribonuclease in eukaryotes, which degrades deadenylated and decapped mRNAs in the last step of the 5′–3′ mRNA decay pathway. Metazoan XRN1 interacts with decapping factors coupling the final stages of decay. Here, we reveal a direct interaction between XRN1 and the CCR4–NOT deadenylase complex mediated by a low-complexity region in XRN1, which we term the ‘C-terminal interacting region’ or CIR. The CIR represses reporter mRNA deadenylation in human cells when overexpressed and inhibits CCR4–NOT and isolated CAF1 deadenylase activity in vitro. Through complementation studies in an XRN1-null cell line, we dissect the specific contributions of XRN1 domains and regions toward decay of an mRNA reporter. We observe that XRN1 binding to the decapping activator EDC4 counteracts the dominant negative effect of CIR overexpression on decay. Another decapping activator PatL1 directly interacts with CIR and alleviates the CIR-mediated inhibition of CCR4–NOT activity in vitro. Ribosome profiling revealed that XRN1 loss impacts not only on mRNA levels but also on the translational efficiency of many cellular transcripts likely as a consequence of incomplete decay. Our findings reveal an additional layer of direct interactions in a tightly integrated network of factors mediating deadenylation, decapping and 5′–3′ exonucleolytic decay.

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