Podcast
Questions and Answers
In order to understand what ______ is and how it works, we need to consider or remember our basics in molecular biology.
In order to understand what ______ is and how it works, we need to consider or remember our basics in molecular biology.
siRNA
The diagram shows the process of ______, namely the encoding of mRNA from DNA, thereafter the generation of proteins using the mRNA code in a process called translation, and the further modification of proteins via post-translational modification events.
The diagram shows the process of ______, namely the encoding of mRNA from DNA, thereafter the generation of proteins using the mRNA code in a process called translation, and the further modification of proteins via post-translational modification events.
transcription
In a case where too much of a protein is generated or if a mutated protein function needs to be inhibited, we need a way to stop this over production or ______.
In a case where too much of a protein is generated or if a mutated protein function needs to be inhibited, we need a way to stop this over production or ______.
misfunction
______ technology is a powerful method to prevent protein production.
______ technology is a powerful method to prevent protein production.
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SiRNA molecules are small bits of RNA that target and assist in the ______ of mRNA, such that protein translation is limited or blocked.
SiRNA molecules are small bits of RNA that target and assist in the ______ of mRNA, such that protein translation is limited or blocked.
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Imagine in Step 1 that a mammalian cell is infected by a ______.
Imagine in Step 1 that a mammalian cell is infected by a ______.
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This virus contains double-stranded RNA. Upon entry into the cell, in Step 2, an enzyme called ______ cuts the viral RNA into smaller parts generating fragments of RNA.
This virus contains double-stranded RNA. Upon entry into the cell, in Step 2, an enzyme called ______ cuts the viral RNA into smaller parts generating fragments of RNA.
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In Step 3, these small pieces of RNA are recognised by the RISC ______.
In Step 3, these small pieces of RNA are recognised by the RISC ______.
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The main benefit of ______ peptides is their rapid design.
The main benefit of ______ peptides is their rapid design.
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Once trafficking proteins are identified, ______ sites between the receptor and the protein can be quickly determined.
Once trafficking proteins are identified, ______ sites between the receptor and the protein can be quickly determined.
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The blocking peptide can be made to match a short ______ sequence.
The blocking peptide can be made to match a short ______ sequence.
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At high concentrations, blocking peptides compete with the receptor for binding to the ______ protein.
At high concentrations, blocking peptides compete with the receptor for binding to the ______ protein.
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One disadvantage of receptor blocking peptides is their poor ______.
One disadvantage of receptor blocking peptides is their poor ______.
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Another challenge is the possibility of an ______ response.
Another challenge is the possibility of an ______ response.
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Delivering these peptides to the correct location within the body is a ______.
Delivering these peptides to the correct location within the body is a ______.
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The technology of receptor blocking peptides remains at the ______ stage.
The technology of receptor blocking peptides remains at the ______ stage.
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Surface expression is controlled by three events: ______, exocytosis, and localisation.
Surface expression is controlled by three events: ______, exocytosis, and localisation.
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Exocytosis is the ______ of receptors into the cell surface.
Exocytosis is the ______ of receptors into the cell surface.
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Localisation refers to the ______ location of the receptor at the cell surface.
Localisation refers to the ______ location of the receptor at the cell surface.
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Protein interactions are important for ______ receptor surface expression.
Protein interactions are important for ______ receptor surface expression.
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Scaffolding proteins are also known as proteins that ______ receptors at the membrane.
Scaffolding proteins are also known as proteins that ______ receptors at the membrane.
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Trafficking and scaffold proteins often have ______ domains that allow them to bind receptors and other proteins.
Trafficking and scaffold proteins often have ______ domains that allow them to bind receptors and other proteins.
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Trafficking and scaffold proteins can bind to and ______ receptor trafficking and placement.
Trafficking and scaffold proteins can bind to and ______ receptor trafficking and placement.
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This slide shows more examples of receptor ______ and scaffolding proteins.
This slide shows more examples of receptor ______ and scaffolding proteins.
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The major drug targets are considered to be receptors and ______.
The major drug targets are considered to be receptors and ______.
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Biologics include large peptides, recombinant proteins, and ______.
Biologics include large peptides, recombinant proteins, and ______.
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The first biologic drug was humanised ______, which became available in 1982.
The first biologic drug was humanised ______, which became available in 1982.
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There has been a substantial increase in the commercialisation of cell therapy and medical ______.
There has been a substantial increase in the commercialisation of cell therapy and medical ______.
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In 2010, only six biologics were approved, while 15 biologics were approved in ______.
In 2010, only six biologics were approved, while 15 biologics were approved in ______.
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Small molecules such as drugs include receptor agonists, receptor antagonists, and enzyme ______.
Small molecules such as drugs include receptor agonists, receptor antagonists, and enzyme ______.
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Biologic drugs are dominating the commercial ______ space.
Biologic drugs are dominating the commercial ______ space.
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There has been a focus on small molecules being the major types of drugs on the ______.
There has been a focus on small molecules being the major types of drugs on the ______.
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Aptamers are about a tenth of the size of ______.
Aptamers are about a tenth of the size of ______.
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Aptamers have low or no ______.
Aptamers have low or no ______.
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Aptamers can survive throughout various organs of the body, including the ______.
Aptamers can survive throughout various organs of the body, including the ______.
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One limitation of aptamers is that they are not as well-characterised or widely used as ______.
One limitation of aptamers is that they are not as well-characterised or widely used as ______.
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Aptamers can be used for target ______.
Aptamers can be used for target ______.
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Aptamers can be conjugated to a ______ for target delivery.
Aptamers can be conjugated to a ______ for target delivery.
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The hope in target discovery is to identify aptamers that bind ______ cells.
The hope in target discovery is to identify aptamers that bind ______ cells.
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Aptamers can also help create drug targets or ______ linked to diseased cells.
Aptamers can also help create drug targets or ______ linked to diseased cells.
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In 2021, 12 of the top 20 drugs were __________.
In 2021, 12 of the top 20 drugs were __________.
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The vaccine developed by Pfizer is called __________.
The vaccine developed by Pfizer is called __________.
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AbbVie’s drug used for arthritis and Crohn's is known as __________.
AbbVie’s drug used for arthritis and Crohn's is known as __________.
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The drug known as __________ is a PD1 mAB used for treating cancers.
The drug known as __________ is a PD1 mAB used for treating cancers.
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The drug used as an anticoagulant for deep vein thrombosis is __________.
The drug used as an anticoagulant for deep vein thrombosis is __________.
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Regeneron's COVID-19 treatment, known as __________, is a vaccine.
Regeneron's COVID-19 treatment, known as __________, is a vaccine.
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Trulicity is an analogue of human __________ used to treat Type 2 diabetes.
Trulicity is an analogue of human __________ used to treat Type 2 diabetes.
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Th drug __________ is used in the treatment of multiple myeloma and is known as CD38 mAB.
Th drug __________ is used in the treatment of multiple myeloma and is known as CD38 mAB.
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The vaccine Gardasil 9 targets __________ virus.
The vaccine Gardasil 9 targets __________ virus.
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The drug __________ is a CDK 4/6 inhibitor used for breast cancer.
The drug __________ is a CDK 4/6 inhibitor used for breast cancer.
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Flashcards
Major Drug Targets
Major Drug Targets
Receptors and enzymes primarily targeted by drugs for treatment.
Molecular Drug Targets
Molecular Drug Targets
Drug targets including DNA, mRNA, and proteins, beyond traditional receptors and enzymes.
Types of Drugs
Types of Drugs
Includes receptor agonists, antagonists, and enzyme inhibitors, mainly small molecules.
Biologics
Biologics
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First Biologic Drug
First Biologic Drug
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Biologics Approval Increase
Biologics Approval Increase
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Commercialization of Biologics
Commercialization of Biologics
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Therapeutic Sector Growth
Therapeutic Sector Growth
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Aptamer size
Aptamer size
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Blood Brain Barrier (BBB)
Blood Brain Barrier (BBB)
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Immunogenicity of Aptamers
Immunogenicity of Aptamers
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Stability of Aptamers
Stability of Aptamers
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Manufacturing of Aptamers
Manufacturing of Aptamers
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Limitations of Aptamers
Limitations of Aptamers
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Target Discovery
Target Discovery
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Target Delivery
Target Delivery
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Transcription
Transcription
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Translation
Translation
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Post-translational modification
Post-translational modification
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siRNA
siRNA
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RISC complex
RISC complex
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DICER
DICER
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Gene silencing
Gene silencing
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Discovery of siRNA
Discovery of siRNA
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Antibodies
Antibodies
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Vaccine
Vaccine
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COVID-19 Drugs
COVID-19 Drugs
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Humira
Humira
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Keytruda
Keytruda
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mAb
mAb
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Anticoagulant
Anticoagulant
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Type 2 Diabetes Drug
Type 2 Diabetes Drug
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Receptor Blocking Peptides
Receptor Blocking Peptides
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Design Advantage
Design Advantage
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Binding Sites
Binding Sites
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High Concentrations
High Concentrations
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Disadvantages of Peptides
Disadvantages of Peptides
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Immune Response
Immune Response
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Delivery Challenges
Delivery Challenges
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Commercialization Status
Commercialization Status
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Endocytosis
Endocytosis
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Exocytosis
Exocytosis
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Localisation
Localisation
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Scaffolding Proteins
Scaffolding Proteins
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Receptor Trafficking
Receptor Trafficking
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Receptor Insertion
Receptor Insertion
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Receptor Removal
Receptor Removal
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Multip-domain Proteins
Multip-domain Proteins
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Study Notes
Molecular-Based Therapies and Technologies
- This presentation reviews molecular-based therapies like siRNA, aptamers, and blocking peptides.
- It explores their mechanisms of action and current market status.
- Key drug targets include proteins and enzymes.
- Biologics (antibodies, proteins, peptides) are increasingly prevalent in the commercial market, with > 12 of 20 top-selling drugs in 2021 being biologics.
- Biologics have a history dating back to 1982 with humanized insulin as a first example. This field has seen substantial growth in recent years with numerous new developments including cell therapy and medical devices.
Overview of Drugs and Drug Targets
- Major drug targets are proteins (receptors, enzymes), DNA and mRNA.
- Small molecule drugs and biologic drugs are distinct types of drugs targeting these molecules.
- The drug targets are areas on a protein/molecule to which a drug can attach. There are ways to manipulate the drug target/proteins to either activate, inhibit or modify it. Active, inactive and specific are terms associated with how the drug binds to the target.
A Brief History of Biologics
- First biologic drug was humanized insulin, appearing in 1982.
- Current biologics encompass a variety of molecules (large peptides, recombinant proteins, antibodies, DNA/RNA-based, synthetic vaccines).
- The number of approved biologics has grown significantly since 2010.
Top 20 Drugs in 2021
- 12 of the top 20 selling drugs in 2021 were biologics (antibodies, vaccines, or protein-based).
- Pfizer's Comirnaty ($36.8 billion), for COVID-19, was notably top-selling.
Section 1: Small Interfering RNA (siRNA)
- siRNA is a small interfering RNA molecule targeting mRNA for protein production elimination.
- It operates using a process called RNA-induced silencing complex (RISC).
- It involves a series of key steps of cutting mRNA (inducing gene silencing) to stop proteins from being made.
Our Antiviral Defense
- Cells have antiviral defense mechanisms which involve cutting viral RNA into smaller pieces (siRNA).
- These pieces are then recognised by a complex, RISC, and then bind to specific viral mRNA.
- DICER-enzyme cuts viral RNA into small fragments (siRNA).
- The siRNA complex binds viral mRNA, cutting it and preventing protein production.
How siRNA Works
- siRNA sequences are designed to match mRNA targets.
- Cells receive and incorporate artificial siRNA or viral-based mRNA.
- RNA-induced silencing complex (RISC) binds to a strand of siRNA.
- The subsequent binding of RISC to compatible mRNA causes cuts to the mRNA, stopping related protein formation.
siRNA Market Story
- siRNA technology has shown potential but hasn't yet reached full market success.
- The target areas for siRNA include eyes, lungs, liver, skin, kidney, and tumours.
- Companies using this technology have varied success rates.
Section 2: Aptamers
- Aptamers are single-stranded DNA or RNA molecules selectively binding targets.
- They form specific 3D structures to have a well fit for the proteins they target.
- The process of finding an effective aptamer is called Systematic Evolution of Ligands by Exponential Enrichment (SELEX).
- Key steps include creating a wide library of molecules, identifying aptamers, amplifying the selected aptamers and choosing the one with highest affinity for the target protein.
Uses of Aptamers
- Target Discovery: Identifying aptamers specific to diseased cells vs. healthy cells for drug development and biomarker identification.
- Target Delivery: Attaching aptamers to drugs to target specific cells or tissues.
- Toxin Removal: Removing toxins by targeting bound toxin to specific removal organs/ systems in the body).
- Drug Labeling: Attaching fluorescent tags to aptamers for tracking drug distribution and metabolism.
Section 3: Blocking Peptides
- Blocking peptides act as regulators of receptor function (activate or deactivate).
- Specific peptides are tailored to interact with receptor-trafficking and scaffold proteins.
- They prevent receptors from binding to trafficking proteins, thus controlling receptor placement and ultimately affecting receptor function.
Receptors as Drug Targets
- Important methods used to regulate receptor function include agonists, partial agonists, antagonists and inverse agonists.
- Methods and challenges related to receptor function regulation are discussed in detail.
Novel Methods to Alter Receptor Function
- Regulation of receptor trafficking to cell surfaces and maintaining them inside the cell are areas of potential use to manipulate receptor function.
- Targeting receptor placement affects the function of the receptor.
Multiple Domain Protein Scaffolds
- Proteins have multiple domains allowing receptors to be grouped for appropriate function.
- These proteins work together to regulate receptor trafficking and placement.
Receptor Trafficking and Anchoring Proteins
- Specific proteins are involved in receptor trafficking and anchoring.
- These proteins regulate where receptors are located within the cell.
Postsynaptic Density: Full of Proteins
- Many proteins are present at the postsynaptic density, the central site of the neuron.
- Proteins are involved in regulating trafficking to and from the membrane.
Creating Blocking Peptides to Inhibit Interactions
- Steps for creating blocking peptides to regulate receptor function are described.
- This process of using peptides involves identifying the right protein and binding sites.
Blocking Peptides as Receptor Activators
- Methods using blocking peptides to promote receptor function are detailed.
Benefits and Challenges of Blocking Peptides
- Benefits like quick design and high concentrations blocking interaction are described.
- Challenges like instability, poor distribution, immune response when delivered to the target are described
Blocking Peptides Market Story
- This technology has not yet seen broad market application.
- It is currently being researched in academic labs.
Conclusion
- siRNA, aptamers, and blocking peptides offer novel approaches to receptor pharmacology.
- These techniques hold potential but further research and development are needed.
- These technologies represent novel approaches to classic receptor pharmacology.
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Description
This quiz covers the essentials of molecular-based therapies including siRNA, aptamers, and biologics. It explores key drug targets such as proteins and their significance in the pharmaceutical market. Understand the relationship between drugs and their target molecules for a comprehensive insight into modern therapeutics.
