Correction for Bell Et Al., in Silico Design and Validation of High-Affinity RNA Aptamers Targeting Epithelial Cellular Adhesion
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Mrna Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection
International Journal of Molecular Sciences Review mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection 1, 1, 2 1,3, Shuqin Xu y, Kunpeng Yang y, Rose Li and Lu Zhang * 1 State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200438, China; [email protected] (S.X.); [email protected] (K.Y.) 2 M.B.B.S., School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; [email protected] 3 Shanghai Engineering Research Center of Industrial Microorganisms, Shanghai 200438, China * Correspondence: [email protected]; Tel.: +86-13524278762 These authors contributed equally to this work. y Received: 30 July 2020; Accepted: 30 August 2020; Published: 9 September 2020 Abstract: Messenger ribonucleic acid (mRNA)-based drugs, notably mRNA vaccines, have been widely proven as a promising treatment strategy in immune therapeutics. The extraordinary advantages associated with mRNA vaccines, including their high efficacy, a relatively low severity of side effects, and low attainment costs, have enabled them to become prevalent in pre-clinical and clinical trials against various infectious diseases and cancers. Recent technological advancements have alleviated some issues that hinder mRNA vaccine development, such as low efficiency that exist in both gene translation and in vivo deliveries. mRNA immunogenicity can also be greatly adjusted as a result of upgraded technologies. In this review, we have summarized details regarding the optimization of mRNA vaccines, and the underlying biological mechanisms of this form of vaccines. Applications of mRNA vaccines in some infectious diseases and cancers are introduced. It also includes our prospections for mRNA vaccine applications in diseases caused by bacterial pathogens, such as tuberculosis. -
In Silico Tools for Splicing Defect Prediction: a Survey from the Viewpoint of End Users
© American College of Medical Genetics and Genomics REVIEW In silico tools for splicing defect prediction: a survey from the viewpoint of end users Xueqiu Jian, MPH1, Eric Boerwinkle, PhD1,2 and Xiaoming Liu, PhD1 RNA splicing is the process during which introns are excised and informaticians in relevant areas who are working on huge data sets exons are spliced. The precise recognition of splicing signals is critical may also benefit from this review. Specifically, we focus on those tools to this process, and mutations affecting splicing comprise a consider- whose primary goal is to predict the impact of mutations within the able proportion of genetic disease etiology. Analysis of RNA samples 5′ and 3′ splicing consensus regions: the algorithms used by different from the patient is the most straightforward and reliable method to tools as well as their major advantages and disadvantages are briefly detect splicing defects. However, currently, the technical limitation introduced; the formats of their input and output are summarized; prohibits its use in routine clinical practice. In silico tools that predict and the interpretation, evaluation, and prospection are also discussed. potential consequences of splicing mutations may be useful in daily Genet Med advance online publication 21 November 2013 diagnostic activities. In this review, we provide medical geneticists with some basic insights into some of the most popular in silico tools Key Words: bioinformatics; end user; in silico prediction tool; for splicing defect prediction, from the viewpoint of end users. Bio- medical genetics; splicing consensus region; splicing mutation INTRODUCTION TO PRE-mRNA SPLICING AND small nuclear ribonucleoproteins and more than 150 proteins, MUTATIONS AFFECTING SPLICING serine/arginine-rich (SR) proteins, heterogeneous nuclear ribo- Sixty years ago, the milestone discovery of the double-helix nucleoproteins, and the regulatory complex (Figure 1). -
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DNA and RNA Nanotechnology 2015; 2: 42–52 Mini review Open Access Martin Panigaj*, Jakob Reiser Aptamer guided delivery of nucleic acid-based nanoparticles DOI 10.1515/rnan-2015-0005 Evolution of Ligands by Exponential enrichment) [4,5]. Received July 15, 2015; accepted October 3, 2015 Nucleic acid-based aptamers are especially well suited Abstract: Targeted delivery of bioactive compounds is a for the delivery of nucleic acid-based therapeutics. Any key part of successful therapies. In this context, nucleic nucleic acid with therapeutic potential can be linked acid and protein-based aptamers have been shown to to an aptamer sequence [6], resulting in a bivalent bind therapeutically relevant targets including receptors. molecule endowed with a targeting aptamer moiety and In the last decade, nucleic acid-based therapeutics a functional RNA/DNA moiety like a small interfering coupled to aptamers have emerged as a viable strategy for RNA (siRNA), a micro RNA (miRNA), a miRNA antagonist cell specific delivery. Additionally, recent developments (antimiR), deoxyribozymes (DNAzymes), etc. In addition in nucleic acid nanotechnology offer an abundance of to the specific binding, many aptamers upon receptor possibilities to rationally design aptamer targeted RNA recognition elicit antagonistic or agonistic responses that, or DNA nanoparticles involving combinatorial use of in combination with conjugated functional nucleic acids various intrinsic functionalities. Although a host of issues have the potential of synergism. Since the first report including stability, safety and intracellular trafficking describing an aptamer-siRNA delivery approach in 2006 remain to be addressed, aptamers as simple functional many functional RNAs and DNAs conjugated to aptamer chimeras or as parts of multifunctional self-assembled sequences have been tested in vitro and in vivo [7-9]. -
In Silico Protein Design: a Combinatorial and Global Optimization Approach by John L
From SIAM News, Volume 37, Number 1, January/February 2004 In Silico Protein Design: A Combinatorial and Global Optimization Approach By John L. Klepeis and Christodoulos A. Floudas The use of computational techniques to create peptide- and protein-based therapeutics is an important challenge in medicine. The ultimate goal, defined about two decades ago, is to use computer algorithms to identify amino acid sequences that not only adopt particular three-dimensional structures but also perform specific functions. To those familiar with the field of structural biology, it is certainly not surprising that this problem has been described as “inverse protein folding” [16]. That is, while the grand challenge of protein folding is to understand how a particular protein, defined by its amino acid sequence, finds its unique three-dimensional structure, protein design involves the discovery of sets of amino acid sequences that form functional proteins and fold into specific target structures. Experimental, computational, and hybrid approaches have all contributed to advances in protein design. Applying mutagenesis and rational design techniques, for example, experimentalists have created enzymes with altered functionalities and increased stability. The coverage of sequence space is highly restricted for these techniques, however [4]. An approach that samples more diverse sequences, called directed protein evolution, iteratively applies the techniques of genetic recombination and in vitro functional assays [1]. These methods, although they do a better job of sampling sequence space and generating functionally diverse proteins, are still restricted to the screening of 103 – 106 sequences [22]. Challenges of Generic Computational Protein Design The limitations of experimental techniques serve to highlight the importance of computational protein design. -
7 Systems Biotechnology: Combined in Silico and Omics Analyses for The
0195300815_0193-0231_ Ch-07.qxd 23/6/06 4:56 PM Page 193 7 Systems Biotechnology: Combined in Silico and Omics Analyses for the Improvement of Microorganisms for Industrial Applications Sang Yup Lee, Dong-Yup Lee, Tae Yong Kim, Byung Hun Kim, & Sang Jun Lee Biotechnology plays an increasingly important role in the healthcare, pharmaceutical, chemical, food, and agricultural industries. Microorganisms have been successfully employed for the production of recombinant proteins [1–4] and various primary and secondary metabolites [5–8]. As in other engineering disciplines, one of the ulti- mate goals of industrial biotechnology is to develop lower-cost and higher-yield processes. Toward this goal, fermentation and down- stream processes have been significantly improved thanks to the effort of biochemical engineers [9]. In addition to the effort of making these mid- to downstream processes more efficient, microbial strains have been improved by recombinant and other molecular biological methods, leading to the increase in microbial metabolic activities toward desired goals [10]. However, these conventional attempts have not always been successful owing to unexpected changes in the physiology and metabolism of host cells. Alternatively, rational meta- bolic and cellular engineering approaches have been tried to solve such problems in a number of cases, but they were also still limited to the manipulation of only a handful of genes encoding enzymes and regulatory proteins. In this regard, systematic approaches are indeed required not only for understanding the global context of the meta- bolic system but also for designing better metabolic engineering strategies. Recent advances in high-throughput experimental techniques have resulted in rapid accumulation of a wide range of biological data and information at different levels: genome, transcriptome, pro- teome, metabolome, and fluxome [11–17]. -
In Silico Prediction of Protein Flexibility with Local Structure Approach
Bioinformatics protein flexibility prediction Preprint – accepted for publication in Biochimie in silico prediction of protein flexibility with local structure approach. Tarun J. Narwani1,2,3,+, Catherine Etchebest1,2,3,+, Pierrick Craveur1,2,3,4, Sylvain Léonard1,2,3, Joseph Rebehmed1,2,3,5, Narayanaswamy Srinivasan6, Aurélie Bornot1,2,3, #, Jean-Christophe Gelly1,2,3 & Alexandre G. de Brevern1,2,3,4,* 1 INSERM, U 1134, DSIMB, Univ Paris, Univ de la Réunion, Univ des Antilles, F-75739 Paris, France. 2 Institut National de la Transfusion Sanguine (INTS), F-75739 Paris, France. 3 Laboratoire d'Excellence GR-Ex, F-75739 Paris, France. 4 Molecular Graphics Laboratory, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 5 Department of Computer Science and Mathematics, Lebanese American University, Byblos 1h401 2010, Lebanon. 9 MBU, IISc, Bangalore, India # Present address: AstraZeneca, Discovery Sciences, Computational Biology, Alderley Park UK. Short title: bioinformatics protein flexibility prediction * Corresponding author: Mailing address: Dr. de Alexandre G. de Brevern, INSERM UMR_S 1134, DSIMB, Université Paris, Institut National de Transfusion Sanguine (INTS), 6, rue Alexandre Cabanel, 75739 Paris cedex 15, France e-mail : [email protected] 1 Bioinformatics protein flexibility prediction Abstract Flexibility is an intrinsic essential feature of protein structures, directly linked to their functions. To this day, most of the prediction methods use the crystallographic data (namely B-factors) as the only indicator of protein’s inner flexibility and predicts them as rigid or flexible. PredyFlexy stands differently from other approaches as it relies on the definition of protein flexibility (i) not only taken from crystallographic data, but also (ii) from Root Mean Square Fluctuation (RMSFs) observed in Molecular Dynamics simulations. -
Recent Advances in Mrna Vaccine Delivery
Nano Research 2018, 11(10): 5338–5354 https://doi.org/10.1007/s12274-018-2091-z Recent advances in mRNA vaccine delivery Lu Tan and Xun Sun () Key Laboratory of Drug Targeting and Novel Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China Received: 14 March 2018 ABSTRACT Revised: 30 April 2018 In recent years, messenger RNA (mRNA) vaccines have been intensively studied Accepted: 4 May 2018 in the fields of cancer immunotherapy and infectious diseases because of their excellent efficacy and safety profile. Despite significant progress in the rational © Tsinghua University Press design of mRNA vaccines and elucidation of their mechanism of action, their and Springer-Verlag GmbH widespread application is limited by the development of safe and effective Germany, part of Springer delivery systems that protect them from ubiquitous ribonucleases (RNases), Nature 2018 facilitate their entry into cells and subsequent escape from endosomes, and target them to lymphoid organs or particular cells. Some mRNA vaccines based KEYWORDS on lipid carriers have entered clinical trials. Vaccines based on polymers, while messenger RNA (mRNA) not as clinically advanced as lipid vectors, show considerable potentials. In this vaccines, review, we discuss the necessity of formulating mRNA vaccines with delivery delivery systems, systems, and we provide an overview of reported delivery systems. polymer, lipid 1 Introduction and their complex composition can trigger adverse effects [3]. In contrast, mRNA vaccines express well- Messenger RNA (mRNA) vaccines carry transcripts defined antigens that induce focused immune responses encoding antigens, and use the host cell translational specifically against the encoded antigens [4]. -
RNA-Based Therapeutics: Current Progress and Future Prospects
CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Chemistry & Biology Review RNA-Based Therapeutics: Current Progress and Future Prospects John C. Burnett1 and John J. Rossi1,* 1Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA *Correspondence: [email protected] DOI 10.1016/j.chembiol.2011.12.008 Recent advances of biological drugs have broadened the scope of therapeutic targets for a variety of human diseases. This holds true for dozens of RNA-based therapeutics currently under clinical investigation for diseases ranging from genetic disorders to HIV infection to various cancers. These emerging drugs, which include therapeutic ribozymes, aptamers, and small interfering RNAs (siRNAs), demonstrate the unprece- dented versatility of RNA. However, RNA is inherently unstable, potentially immunogenic, and typically requires a delivery vehicle for efficient transport to the targeted cells. These issues have hindered the clinical progress of some RNA-based drugs and have contributed to mixed results in clinical testing. Nevertheless, promising results from recent clinical trials suggest that these barriers may be overcome with improved synthetic delivery carriers and chemical modifications of the RNA therapeutics. This review focuses on the clinical results of siRNA, RNA aptamer, and ribozyme therapeutics and the prospects for future successes. Introduction synthesizing modified RNA and DNA molecules have increased Since the milestone -
Bioinformatics Glossary Based Database of Biological Databases: DBD
J Biochem Tech (2009) 1(3):88-90 ISSN: 0974-2328 Bioinformatics glossary based Database of Biological Databases: DBD Siva Kiran RR, Setty MVN, Hanumatha Rao G* Received: 16 May 2009 / Received in revised form: 17 May 2009, Accepted: 18 May 2009, Published online: 6 June 2009 © Sevas Educational Society 2008 Abstract Database of Biological/Bioinformatics Databases (DBD) is a Databases of Biological Databases such as DOD – Database of collection of 1669 databases and online resources collected from Databases (http://www.progenebio.in/DoD/DoD.htm), MetaBase - NAR Database Summary Papers (http://www.oxfordjournals.org The Database of Biological Database (http://biodatabase.org) and /nar/database/a/) & Internet search engines. The database has been The Molecular Biology Database Collection – Updates developed based on 437 keywords (Glossary) available in (Baxevanis 2000), published annually by journal entitled “Nucleic http://falcon.roswellpark.org/labweb/glossary.html. Keywords with Acids Research” help researchers to identify and correlate important their relevant databases are arranged in alphabetic order which queries beside providing a common platform for various molecular enables quick accession of databases by researchers. Database biology databases. Databases in DOD, Metabase & others have been description provides brief information about the database with a link grouped into categories as conceived by the respective authors. For to main web page. DBD is available online and can be accessed at instance, DOD has grouped 719 databases into 14 major categories http://www.biodbs.info. (Galperin 2005) while Metabase has grouped 1119 databases into 21 categories. Keywords: Databases, biological databases, bioinformatics databases, bioinformatics glossary The uniqueness of the present DBD is the alphabetic listing of all databases based on technical terms (keywords) viz. -
In Silico Analysis of Protein 211012, Uttar Pradesh, India, Tel: 9450900033; Email
Central JSM Bioinformatics, Genomics and Proteomics Bringing Excellence in Open Access Research Article *Corresponding author Nidhi Mishra, CC-III, Indian Institute of Information Technology Allahabad, Devghat, Jhalwa, Allahabad- In silico Analysis of Protein 211012, Uttar Pradesh, India, Tel: 9450900033; Email: Nishtha Singh, Sonal Upadhyay, Ankur Jaiswar and Nidhi Submitted: 28 June 2016 Mishra* Accepted: 31 August 2016 Applied Science Division, Indian Institute of Information Technology, India Published: 07 September 2016 Copyright Abstract © 2016 Mishra et al. Proteins are inimitable as principal functional agent of living system. Therefore, OPEN ACCESS comprehension of protein sequence and structure and its correlation with its function is equivalent to deciphering almost all of fundamental features of any biological/living Keywords system. A treasure of In silico tools is accessible for analysis of protein. Understanding • Protein analysis and regeneration of protein function requires comprehension of reliance between • In Silico protein sequence and its structure, its localization in cell and its interaction with other • Function functional partners. This review provides an insight for various tools for In silico analysis • Sequence of protein. • Tools ABBREVIATIONS psi-blast (it establishes distant relationship between proteins), blastx (comparison of six-frame translation product of query UNIPROT: Universal Protein Resource; FASTA: FAST sequence of nucleotide against database of protein sequence) Alignment; BLAST: Basic Local Alignment Search Tool; Blastn: , tblastx (comparison of six-frame translation product of query Nucleotide Basic Local Alignment Search Tool; Blastp: Protein sequence of nucleotide against database of nucleotide sequence) andtblastn (comparison of protein query sequence against six Iterated Basic Local Alignment Search Tool; SOPMA: Self reading frames of database of nucleotide sequence) [2]. -
Covid 3 Edward Hammond.Pmd
TWN Series on Intellectual Property and COVID-19 TWNT h i r d W o r l d N e t w o r k Vaccines www.twn.my 3 August 2020 Patent dispute looms as a major complication for Moderna’s COVID-19 vaccine Edward Hammond Moderna’s candidate COVID-19 vaccine, mRNA-1273, on which the US government has placed one of its largest pandemic bets, appears to be ensnared in a serious patent dispute that could impact the vaccine’s production and price. The problem lies in a fight between Moderna and a Canadian biotech company named Arbutus, formerly Tekmira, which holds a patent on mRNA vaccine formulations that Moderna’s vaccine may infringe on. Moderna denies that it needs a licence to Arbutus’ patent in order to produce mRNA-1273.1 But a recent pre- publication paper with Moderna co-authors2 states that mRNA-1273’s formulation is one that appears to squarely fall within the claims of a 2011 Arbutus patent3 that covers particular ratios of ingredients in an mRNA vaccine. Although the pre-publication paper was released only weeks ago in mid-June, Moderna claims that the mRNA-1273 composition that it describes is a “research formulation” that will be replaced with an alternative when the vaccine goes into production. Asked to describe the new formulation, Moderna declined, telling Forbes magazine that “we are not disclosing our proprietary ratios at this time.”4 Before the pandemic, Moderna was working with United States government support on a vaccine against MERS (Middle East Respiratory Syndrome), a coronavirus “cousin” of SARS-CoV-2 that causes COVID- 19. -
Small Interfering RNA from the Lab Discovery to Patients' Recovery
Small interfering RNA from the lab discovery to patients’ recovery Marie Caillaud, Mévidette El Madani, Liliane Massaad-Massade To cite this version: Marie Caillaud, Mévidette El Madani, Liliane Massaad-Massade. Small interfering RNA from the lab discovery to patients’ recovery. Journal of Controlled Release, Elsevier, 2020, 321, pp.616-628. 10.1016/j.jconrel.2020.02.032. hal-02988620 HAL Id: hal-02988620 https://hal.archives-ouvertes.fr/hal-02988620 Submitted on 19 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 1 Small interfering RNA from the lab discovery to patients’ recovery 2 3 Marie Caillaud1, Mévidette El Madani1 and, Liliane Massaad-Massade1* 4 5 1 Université Paris-Saclay, Inserm 1195, Bâtiment Gregory Pincus, 80 rue du Général Leclerc, 6 94276 Le Kremlin-Bicêtre, France 7 8 9 1 *: Correspondance to Liliane MASSADE, PhD, Université Paris-Saclay, Inserm 1195, 10 Bâtiment Gregory Pincus, 80 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre, France 11 12 13 Key words : siRNA, delivery, nanotechnology, formulation, galenic, clinical studies 14 1 1 Abstract 2 In 1998, the RNA interference discovery by Fire and Mello revolutionized the scientific and 3 therapeutic world.