Therapeutic Interfering Particle
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Therapeutic Interfering Particle
A therapeutic interfering particle is an antiviral preparation that reduces the replication rate and pathogenesis of a particular viral infectious disease. A therapeutic interfering particle is typically a biological agent (i.e., nucleic acid) engineered from portions of the viral genome being targeted. Similar to Defective Interfering Particles (DIPs), the agent competes with the pathogen within an infected cell for critical viral replication resources, reducing the viral replication rate and resulting in reduced pathogenesis. But, in contrast to DIPs, TIPs are engineered to have an in vivo basic reproductive ratio ( R0) that is greater than 1 ( R0>1). The term "TIP" was first introduced in 2011 based on models of its mechanism-of-action from 2003. Given their unique R0>1 mechanism of action, TIPs exhibit high barriers to the evolution of antiviral resistance and are predicted to be resistance proof. Intervention with therapeutic interfering particles can be prophylactic (to prev ...
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Defective Interfering Particle
Defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication or non-homologous recombination. The mechanism of their formation is presumed to be as a result of template-switching during replication of the viral genome, although non-replicative mechanisms involving direct ligation of genomic RNA fragments have also been proposed. DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection. A DIP can usually still penetrate host cells, but requires another fully functional virus particle (the 'helper' virus) to co-infect a cell with it, in order to provide the lost factors. DIPs were first observed as early as the 1950s by Von Magnus and Schlesinge ...
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Basic Reproduction Number
In epidemiology, the basic reproduction number, or basic reproductive number (sometimes called basic reproduction ratio or basic reproductive rate), denoted R_0 (pronounced ''R nought'' or ''R zero''), of an infection is the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. The definition assumes that no other individuals are infected or immunized (naturally or through vaccination). Some definitions, such as that of the Australian Department of Health, add the absence of "any deliberate intervention in disease transmission". The basic reproduction number is not necessarily the same as the effective reproduction number R (usually written R_t 't'' for time sometimes R_e), which is the number of cases generated in the current state of a population, which does not have to be the uninfected state. R_0 is a dimensionless number (persons infected per person infecting) and not a time rate, which would have units ...
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Defective Interfering Particle
Defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication or non-homologous recombination. The mechanism of their formation is presumed to be as a result of template-switching during replication of the viral genome, although non-replicative mechanisms involving direct ligation of genomic RNA fragments have also been proposed. DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection. A DIP can usually still penetrate host cells, but requires another fully functional virus particle (the 'helper' virus) to co-infect a cell with it, in order to provide the lost factors. DIPs were first observed as early as the 1950s by Von Magnus and Schlesinge ...
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Competitive Inhibition
Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected by this principle, but several classes of competitive inhibition are especially important in biochemistry and medicine, including the competitive form of enzyme inhibition, the competitive form of receptor antagonism, the competitive form of antimetabolite activity, and the competitive form of poisoning (which can include any of the aforementioned types). Enzyme inhibition type In competitive inhibition of enzyme catalysis, binding of an inhibitor prevents binding of the target molecule of the enzyme, also known as the substrate. This is accomplished by blocking the binding site of the substrate – the active site – by some means. The Vmax indicates the maximum velocity of the reaction, while the Km is the amount of substrate needed to r ...
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Interferon
Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses. IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections. However, virus-encoded genetic elements have the ability to antagonize the IFN response contributing to viral pathogenesis and viral diseases. IFNs also have various other functions: they activate immune cells, such as natural killer cells and macrophages, and they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex (M ...
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Virus-like Particle
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly (i.e., assembly inside E. coli bacteria via recombinant co-expression of multiple proteins) and in-vitro assembly (i.e., protein self-assembly in a reaction vessel using stoichiometric quantities of previously purified proteins) have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae (e.g. adeno-associ ...
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Preben Von Magnus
Preben Christian Alexander von Magnus (25 February 1912 – 9 August 1973) was a Danish virologist who is known for his research on influenza, polio vaccination and monkeypox. He gave his name to the Von Magnus phenomenon. In the 1950s, together with his wife the virologist Herdis von Magnus, he directed the first Danish vaccination programme against polio. In 1958, he was the first to confirm the identity of the monkeypox virus and to describe monkeypox in laboratory crab-eating Macaques during two outbreaks of the disease in the summer and autumn of that year. In 1959 he was appointed director of the Statens Serum Institut. He represented Denmark at the 1959 Pugwash Conferences on Science and World Affairs where he explained that respiratory viruses such as influenza and the common cold were unsuitable as biological weapons. He became a Knight of the Order of the Dannebrog in 1965. Early life Preben von Magnus was born in Copenhagen on 25 February 1912 to the Livonian lan ...
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DARPA
The Defense Advanced Research Projects Agency (DARPA) is a research and development agency of the United States Department of Defense responsible for the development of emerging technologies for use by the military. Originally known as the Advanced Research Projects Agency (ARPA), the agency was created on February 7, 1958, by President Dwight D. Eisenhower in response to the Soviet Union, Soviet launching of Sputnik 1 in 1957. By collaborating with academia, industry, and government partners, DARPA formulates and executes research and development projects to expand the frontiers of technology and science, often beyond immediate U.S. military requirements.Dwight D. Eisenhower and Science & Technology, (2008). Dwight D. Eisenhower Memorial CommissionSource ''The Economist'' has called DARPA the agency "that shaped the modern world," and pointed out that "Moderna COVID-19 vaccine, Moderna's COVID-19 vaccine sits alongside weather satellites, Global Positioning System, GPS, Unmann ...
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National Institutes Of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1880s and is now part of the United States Department of Health and Human Services. The majority of NIH facilities are located in Bethesda, Maryland, and other nearby suburbs of the Washington metropolitan area, with other primary facilities in the Research Triangle Park in North Carolina and smaller satellite facilities located around the United States. The NIH conducts its own scientific research through the NIH Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. , the IRP had 1,200 principal investigators and more than 4,000 postdoctoral fellows in basic, translational, and clinical research, being the largest biomedical research instit ...
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Clinical Pharmacology
Clinical pharmacology has been defined as "that discipline that teaches, does research, frames policy, gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice". Clinical Pharmacology is inherently a translational discipline underpinned by the basic science of pharmacology, engaged in the experimental and observational study of the disposition and effects of drugs in humans, and committed to the translation of science into evidence-based therapeutics. It has a broad scope, from the discovery of new target molecules to the effects of drug usage in whole populations. The main aim of clinical pharmacology is to generate data for optimum use of drugs and the practice of 'evidence based medicine'. Clinical pharmacologists have medical and scientific training that enables them to evaluate evidence and produce new data through well-designed studies. Clinical pharmacologists must have access to enough patie ...
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Genetic Engineering
Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus. As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or targeted to a specific part of the genome. An organism that is generated through genetic engineering is considered to be genetically modified (GM) an ...
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