
Frontiers in Molecular Pharming: Volume 2
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The advent of large-scale production and clinical trials of drugs developed through diverse production routes - involving viruses, microbes, plants, and animals - has increased the demand for an expanded capacity for pharmaceutical manufacturing. The production and purification of expressed proteins accounts for the bulk of the manufacturing costs for new therapeutics. Several pharmaceutical proteins have been synthesized by exploiting plant genetics allowing producers to override conventional approaches used to manufacture pharmaceuticals. The process of inserting a gene into a host organism for the purpose of harvesting a bioactive molecule for therapeutic use is known as molecular pharming.
Frontiers in Molecular Pharming covers an array of topics relevant to understanding the structure, function, regulation, and mechanisms of action, biochemical significance, and usage of proteins and peptides as biomarkers, therapeutics, and vaccines for animals and humans. The contributions aim to highlight current progress in three areas, including system biology (in vivo characterization of proteins and peptides), molecular pharming for animals and molecular pharming for humans. The book gives special attention to computational biology tools, production platforms and fields (such as immunoinformatics) and applications of molecular pharming (such as veterinary therapeutics). A balance of theoretical concepts and practical applications is provided through 13 chapters.
Frontiers in Molecular Pharming is an invaluable resource for students and researchers of biochemistry, molecular biology, and biotechnology. The book also serves as a springboard for understanding the process of how discoveries in protein and peptide research and its applications are coming to fruition.
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Content
- Cover
- Title
- Copyright
- End User License Agreement
- Contents
- Preface
- List of Contributors
- SECTION I: System Biology - In silico Characterization of Proteins and Peptides
- Tools for Prediction and Validation of Epitopic Regions on Protein Targets for Vaccine Development and Diagnostics
- Soban Tufail1,2, Majid Ali Shah1,2, Maryam Zafar1,2, Mazhar Iqbal1,2, Amjad Ali3, Aamir Shehzad1,2,* and Moazur Rahman1,4,*
- 1. IMMUNE SYSTEM-AN OVERVIEW
- 2. IDENTIFICATION OF EPITOPES
- 3. TARGET SELECTION FOR EPITOPE PREDICTION
- 4. TOOLS FOR PREDICTION OF LINEAR B-CELL EPITOPES
- 5. TOOLS FOR PREDICTION OF CONFORMATIONAL B-CELL EPITOPES
- 6. PREDICTION OF T-CELL EPITOPES
- 6.1. Tools for Prediction of MHC Class I Binding Peptides
- 6.2. Tools for Prediction of MHC Class II Binding Peptides
- 7. FURTHER CONSIDERATIONS
- 8. LIMITATIONS OF EPITOPE PREDICTION TOOLS AND THE WAY FORWARD
- 9. VALIDATION OF B- AND T-CELL EPITOPES
- 9.1. Tools for Validation of B-cell Epitopes
- 9.1.1. Enzyme-Linked Immunosorbent Assay
- 9.1.2. Immunoblotting
- 9.1.3. Virus Neutralization Test
- 9.1.4. Lateral Flow Assay
- 9.2. Tools for Validation of T-Cell Epitopes
- 9.2.1. Mass spectrometry (MS)
- 9.2.2. Enzyme-linked Immune Absorbent Spot (ELISpot)
- 9.2.3. Intracellular Cytokine Staining (ICS) Assay
- 9.2.4. Tetramer Staining
- CONCLUDING REMARKS
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- Immunoinformatics and its Role in Vaccine Development
- Iqra Mehmood1, Amna Bari2, Sajjad Ahmad3, Anam Naz4, Farah Shahid1, Usman Ali Ashfaq1, Kishver Tusleem5 and Muhammad Tahir ul Qamar6,*
- 1. INTRODUCTION
- 2. TRANSFORMATION OF VACCINOLOGY FROM CONVENTIONAL TO MODERN ERA
- 3. SUBTRACTIVE GENOMICS AND REVERSE VACCINOLOGY
- 3.1. Epitope Based Vaccine Design
- 3.2. Multiple Epitope Sub-unit Vaccines
- 3.3. Antigen Based Vaccine Design
- 4. RECENT ADVANCEMENTS IN IMMUNOINFORMATICS
- 4.1. B and T Cell Epitope Prediction Tools and Databases
- 4.2. Allergens Informatics
- 5. IMMUNOINFORMATICS QUEST AGAINST SARS-COV-2
- 6. LIMITATIONS OF IMMUNOINFORMATICS
- 7. FUTURE PERSPECTIVE AND CONCLUSIONS
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGMENTS
- REFERENCES
- Computational Toolbox for Analysis of Protein Thermostability
- Syed Farhat Ali1,*
- 1. INTRODUCTION
- 2. BASIS OF PROTEIN THERMOSTABILITY
- 2.1. Electrostatic Interactions
- 2.2. Hydrogen Bonds
- 2.3. Hydrophobic Interaction
- 2.4. Disulfide Bonds
- 2.5. Protein Rigidity and Flexibility
- 2.6. Amino Acid Composition
- 3. TOOLS AND APPROACHES FOR IN SILICO ANALYSIS OF PROTEIN THERMOSTABILITY
- 3.1. FireProt
- 3.2. ScooP
- 3.3. KStable
- 3.4. CUPSAT
- 3.5. PROTS
- 3.6. FoldX
- 3.7. RankProt
- 3.8. iStable2.0
- 3.9. Rosetta Design
- 3.10. Comparative Analysis of Tools for Thermostability Prediction
- 4. RELEVANT DATABASES
- 5. APPLICATIONS OF IN SILICO APPROACHES FOR PROTEIN THERMOSTABILITY ANALYSIS AND IMPROVEMENT
- CONCLUSION
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGMENTS
- REFERENCES
- Pan-Proteomics to Analyze the Functional Complexity of Organisms
- Muhammad Tahir ul Qamar1,2, Barira Zahid3, Fatima Khalid3, Anam Naz4, Jia-Ming Song1,2, Sajjad Ahmad5, Xitong Zhu2, Feng Xing6, Muhammad Sarwar Khan7 and Ling-Ling Chen1,2,*
- 1. INTRODUCTION
- 2. CONCEPT OF PAN-PROTEOMICS
- 3. APPROACHES AND SOFTWARE USED FOR PAN-PROTEOMICS
- 4. APPLICATIONS AND EXPERIMENTAL DESIGN OF PAN-PROTEOMICS IN PROKARYOTES RESEARCH
- 4.1. Proteome Retrieval and Removal of Duplicate Sequences
- 4.2. Searching of essential, non-homologous proteins
- 4.3. Metabolic pathway analysis
- 4.4. Drug-Ability Analysis
- 4.5. Prediction of Subcellular Localization
- 5. APPLICATION OF PAN-PROTEOMICS IN EUKARYOTES RESEARCH
- 5.1. Utilization in Plant's Research
- 5.2. Utilization in Animals and Human Research
- 5.3. Utilization in Cancer Studies
- CONCLUSIONS AND FUTURE PERSPECTIVES
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGMENTS:
- REFERENCES
- Functional Characterization of Proteins and Peptides Using Computational Approaches
- Zeshan Haider1,2 and Adnan K. Niazi1,*
- 1. INTRODUCTION
- 2. IN-SILICO ANALYSIS OF PEPTIDES
- 2.1. Classification and Databases of Peptides
- 2.2. Algorithm for Prediction of Peptides and their Function
- 2.2.1. Search for Similar Fragments
- 2.2.2. Search for Evolutionary Conservation
- 2.2.3. Search for Statistical Patterns
- 2.3. Prediction Features for Prediction of Peptides Model
- 2.3.1. Amino Acid Composition
- 2.3.2. Atomic Composition of Amino Acids
- 2.3.3. Chemical Descriptors
- 3. IN-SILICO ANALYSIS OF PROTEINS
- 3.1. Protein Databases for Sequence Retrieval
- 3.1.1. Organism-specific and Protein Family Based-databases
- 3.1.2. Protein Family-Based Databases
- 3.1.3. Organism Specified Protein Databases
- 3.2. Classification of Protein Sequences
- 3.2.1. Methods for Classification of Protein Sequences
- 3.2.2. Signatures Databases for Protein
- 3.2.3. Super Integrated Signatures Databases for Proteins
- 4. MOLECULAR DOCKING-BASED PEPTIDE PREDICTION
- CONCLUSION
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- SECTION II: Molecular Pharming for Human Beings
- Molecular Pharming: Research, Developments and Future Perspective
- Muhammad Sarwar Khan1,*, Ghulam Mustafa1 and Faiz Ahmad Joyia1
- 1. INTRODUCTION
- 2. HISTORY OF THE BIOPHARMACEUTICAL INDUSTRY
- 3. VARIOUS PRODUCTION SYSTEMS FOR BIOPHARMACEUTICALS
- 3.1. Using Microbes for Biopharming
- 3.2. Using Mammalian Cell Lines for Biopharming
- 3.3. Using GM Animals for Biopharming
- 3.4. Using GM Crops for Biopharming
- 4. TYPES OF PLANT-BASED BIOPHARMACEUTICAL PRODUCTS
- 4.1. Antibodies
- 4.2. Vaccines
- 4.3. Other Therapeutic Agents
- 5. TRANSGENIC PLANTS IN THE BIOPHARMACEUTICAL MARKET
- 6. METHODOLOGICAL ASPECTS OF PLANT-BASED BIOPHARMACEUTICALS
- 6.1. Upstream Processing
- 6.1.1. Plant Transformation
- 6.1.2. Media Hydration
- 6.1.3. Cell Culture (Bioreactor)
- 6.2. Harvesting
- 6.2.1. Harvesting from Plant Material (Centrifugation or Filtration)
- 6.3. Downstream Processing of the Proteins of Pharmaceutical Value
- 6.3.1. Protein Extraction
- 6.3.2. Clarification
- 6.3.3. Flocculation
- 6.3.4. Protein Purification
- 7. RECENT ADVANCES IN BIOPHARMACEUTICAL PRODUCTION
- 7.1. Cell and Tissue Culture
- 7.2. Virus-infected Plants - A Valuable Therapeutic Protein Production Source
- 7.3. Expression of Therapeutic Proteins in Plants Through Agro-infection
- 8. QUALITY ASSURANCE IN BIOPHARMACEUTICAL PRODUCTION
- 8.1. Biopharmaceutical Production Validation
- 9. APPLICATIONS OF BIOPHARMACEUTICAL FOR VETERINARY AND HUMANS
- 10. PROSPECTS
- CONSENT FOR PUBLICATION
- CONFLICTS OF INTEREST
- ACKNOWLEDGMENTS
- REFERENCES
- Green Factories: Plants As A Platform For Cost-effective Production of High-value Targets
- Muhammad Omar Khan1, 2, Ayesha Siddiqui1,2 and Niaz Ahmad1,2,*
- 1. WHY PLANT-BASED EXPRESSION SYSTEMS?
- 2. DEVELOPMENT OF TRANSGENIC PLANTS
- 3. SUMMARY AND OUTLOOK
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGMENTS
- REFERENCES
- Analysis of Cross-Reactivity, Specificity and the Use of Optimised ELISA for Rapid Detection of Fusarium Spp.
- Phetole Mangena1,* and Phumzile Mkhize2
- 1. INTRODUCTION
- 2. FUNGAL DISEASES AND HOST RANGE OF FUSARIUM SPP. INFECTING PLANTS AND ANIMALS
- 3. DETECTION SYSTEMS FOR FUSARIUM PATHOGENS
- 3.1. Traditional and Current Methods of Fusarium Detection
- 3.2. Limitations in the Traditional and Current Fusarium Detection Systems
- 4. ANTIBODY REACTIVITY AND SPECIFICITY INVOLVING FUSARIUM SPP.
- 5. NATURE OF ANTIGEN VARIATION AND DISTRIBUTION
- 6. ANTIBODY RECOGNITION
- 6.1. Epitope Structure and Functionality
- 6.2. Paratope Binding
- 6.3. Maturation of Antibody Specificity
- 6.4. Contrast Binding Affinity and Specificity
- 7. DIVERSITY OF FUSARIUM ANTIBODIES AND THEIR SPECIFICITY
- 8. CROSS-REACTIVITY IN MONOCLONAL AND POLYCLONAL ANTIBODIES AGAINST FUSARIUM ANTIGENS
- 9. DEVELOPMENT OF OPTIMISED ELISA FOR RAPID DETECTION OF FUSARIUM SPECIES
- FINAL CONSIDERATIONS OR CONCLUSIONS
- ABBREVIATIONS
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- Plant Molecular Pharming For Human Diseases
- Kiran Saba1, Muhammad Suleman Malik1, Sara Latif1, Fatima Ijaz1, Muhammad Sameeullah2 and Mohammad Tahir Waheed1,*
- 1. INTRODUCTION
- 2. MILLENNIUM DEVELOPMENT GOALS (MDGS)
- 3. SUSTAINABLE DEVELOPMENT GOALS (SDGS)
- 3.1. Role of Plant Molecular Pharming in Achieving Sustainable Development Goals
- 4. CURRENT STATUS OF MOLECULAR PHARMING IN THE LAST DECADE FOR EMERGING INFECTIOUS DISEASES
- 4.1. Chikungunya
- 4.2. Crimean-Congo Hemorrhagic Fever
- 4.3. Ebola Virus Disease
- 4.5. Human Respiratory Syncytial Virus
- 4.6. Influenza
- 4.7. Marburg Virus Disease
- 4.8. Rift Valley Fever
- 4.9. Severe Acute Respiratory Syndrome
- 4.10. Nipah Virus Disease
- 4.11. Zika Virus Disease
- CONCLUDING REMARKS
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- Plant Molecular Farming for Human Therapeutics: Recent Advances and Future Prospects
- Amna Ramzan1, Zainab Y. Sandhu2, Saba Altaf1, Aisha Tarar1, Iqra Arshad1, Sumera Rashid1, Huma Shakoor1, Rabia Abbas1 and Bushra Rashid1,*
- 1. INTRODUCTION
- 2. SIGNIFICANCE OF PLANT MOLECULAR FARMING (PMF) APPLICATIONS
- 2.1. Recombinant Antibodies
- 2.2. Edible Vaccines
- 2.3. Biocatalysts
- 2.4. Biopolymers
- 2.5. Feed Additives
- 2.6. Biofuel
- 3. SUITABLE PLANT MOLECULAR FARMING PRODUCTION SYSTEM
- 3.1. Food/Feed Crops
- 3.2. Non-Food/Feed Crops
- 4. LIMITATIONS AND OPTIMIZATIONS OF PMF PLATFORMS
- 4.1. Optimizing Transcript Expression
- 4.2. Optimizing Protein Stability
- 5. BIOSAFETY AND REGULATORY ISSUES
- 6. POTENTIAL SOLUTIONS FOR BIOSAFETY CONCERNS
- 6.1. Use of Non-Food Crops and Non-Crop Plants
- 6.2. Use of Cell Cultures of Transgenic Plants
- 6.3. Use of Physical and Spatial Containments
- 7. PLANT TRANSFORMATION TECHNIQUES
- 8. PURIFICATION OF RECOMBINANT PROTEIN PRODUCTS
- 9. FUTURE PROSPECTIVE
- CONCLUSION
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- Proteins and Peptides as Biomarkers for Diagnosis of Cardiovascular Diseases
- Sehar Aslam1, Samman Munir1, Muhammad Shareef Masoud1, Usman Ali Ashfaq1, Nazia Nahid1, Mohsin Khurshid2 and Muhammad Qasim1,*
- 1. INTRODUCTION
- 2. BIOMARKERS FOR CVD
- 2.1. Myocardial Stress
- 2.1.1. Atrial Natriuretic Peptides
- 2.1.2. B-type Natriuretic Peptides
- 2.1.3. Copeptin
- 2.2. Myocardial Injury
- 2.2.1. Cardiac Troponin
- 2.2.2. Cardiac Myosin-binding Protein C
- 2.3. Inflammation
- 2.3.1. Interleukin-6
- 2.3.2. C-reactive Protein
- 2.3.3. Galectin-3
- 2.3.4. Growth Differentiation Factor 15 (GDF-15)
- 2.3.5. Suppressor of Tumorigenicity 2 (ST2)
- 2.4. Plaque Instability
- 2.4.1. Matrix Metalloproteinase-9 (MMP-9)
- 2.4.2. Lipoprotein-associated Phospholipase A2 (Lp-PLA2)
- 2.5. Calcium Homeostasis
- 2.5.1. Secretoneurin
- 2.6. Platelet Activation
- 2.6.1. P-selectin
- 2.6.2. CD40 Ligand
- 2.7. Systemic Stress
- 2.7.1. Granin Proteins
- 2.7.2. Catecholamines
- 3. EXPERIMENTAL TECHNIQUES DESIGN FOR SELECTION OF PROTEIN BIOMARKERS OF CARDIOVASCULAR DISEASE
- 4. FROM DISCOVERY TO CLINICAL VALUE: STATUS AND PERSPECTIVE
- 5. MULTI-MARKER APPROACHES
- 6. LIMITATIONS OF PROTEINS/PEPTIDES AS BIOMARKERS FOR CV DISEASES
- CONCLUSION
- CONSENT FOR PUBLICATION
- CONFLICTS OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- SECTION III: Molecular Pharming for Animals
- Veterinary Nutraceutics, Pharmaceutics and Vaccine
- Amjad Islam Aqib1,*, Muhammad Shoaib2, Muhammad Aamir Naseer3, Saad Ahmad4, Mubashrah Mahmood5, Faisal Siddique6, Tean Zaheer7, Aisha Mahmood8 and Iqra Muzammil9
- 1. INTRODUCTION
- 2. VETERINARY ORIGIN NUTRACEUTICS
- 3. VETERINARY PHARMACEUTICS
- 3.1. Role of Transgenic Animals in Pharmaceutical Industry
- 3.2. Hormones and Enzymes of Animal Origin Use in Pharmaceutical Industry
- 3.3. Milk Proteins of Pharmaceutical Importance
- 3.3.1. Bovine Milk Proteins
- 3.3.2. Camel Milk Proteins
- 3.3.3. Sheep / Goat Milk Proteins
- 4. VETERINARY PEPTIDE AND PROTEIN BASED VETERINARY VACCINES
- 4.1. Role of Animals in Passive Immunization
- 4.2. Animal Derived Antibodies
- 4.3. Animal Derived Nanobodies
- 4.3.1. Role of Nanobodies in Drug Delivery and Biomarker Detection
- 4.3.2. Nanobody as an Indicator in Diagnostics and Molecular Imaging
- 4.3.3. The Role of Nanobodies in the Treatment of Diseases
- CONCLUSION
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- Plant Molecular Pharming For Livestock And Poultry
- Rimsha Riaz1, Saher Qadeer1, Faiz Ahmad Joyia1, Ghulam Mustafa1 and Muhammad Sarwar Khan1,*
- 1. INTRODUCTION
- 2. GLOBAL IMPORTANCE OF LIVESTOCK AND POULTRY SECTORS
- 3. ANIMALS TO HUMAN SPREAD OF DISEASES
- 4. EMERGENCE AND RE-EMERGENCE OF NEW DISEASES
- 5. LIMITATIONS OF CURRENTLY USED VACCINES FOR LIVESTOCK AND POULTRY
- 6. TYPES OF VACCINES FOR ANIMALS AND POULTRY
- 6.1. Conventional Live and Inactivated Vaccines:
- 6.2. Subunit Vaccines
- 6.3. Genetically Modified Organisms
- 6.4. DNA-Based Vaccines
- 7. PLANT-BASED EXPRESSION PLATFORM FOR VACCINE PRODUCTION
- 8. IMPORTANT LIVESTOCK AND POULTRY DISEASES AND THEIR PLANT-BASED VACCINES
- 8.1. Infectious Bursal Disease (IBD)
- 8.2. Newcastle Disease (ND)
- 8.3. Foot-and-Mouth Disease (FMD)
- 9. A CURRENT MARKET SCENARIO OF PLANT-BASED THERAPEUTICS FOR LIVESTOCK AND POULTRY DISEASES
- CONSENT FOR PUBLICATION
- CONFLICT OF INTEREST
- ACKNOWLEDGEMENTS
- REFERENCES
- Subject Index
- Back Cover
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