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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Future applications of host direct therapies for infectious disease treatment
1Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
Abstract:
New and emerging pathogens, such as SARS-CoV2 have highlighted the requirement for threat agnostic therapies. Some antibiotics or antivirals can demonstrate broad-spectrum activity against pathogens in the same family or genus but efficacy can quickly reduce due to their specific mechanism of action and for the ability of the disease causing agent to evolve. This has led to the generation of antimicrobial resistant strains, making infectious diseases more difficult to treat. Alternative approaches therefore need to be considered, which include exploring the utility of Host-Directed Therapies (HDTs). This is a growing area with huge potential but difficulties arise due to the complexity of disease profiles. For example, a HDT given early during infection may not be appropriate or as effective when the disease has become chronic or when a patient is in intensive care. With the growing understanding of immune function, a new generation of HDT for the treatment of disease could allow targeting specific pathways to augment or diminish the host response, dependent upon disease profile, and allow for bespoke therapeutic management plans. This review highlights promising and approved HDTs that can manipulate the immune system throughout the spectrum of disease, in particular to viral and bacterial pathogens, and demonstrates how the advantages of HDT will soon outweigh the potential side effects.
Insights
Host-directed therapies (HDTs) offer a promising alternative to traditional antimicrobials for emerging pathogens. This approach manipulates the host immune response for tailored treatment across various disease stages.
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- Emerging pathogens like SARS-CoV2 necessitate novel, adaptable therapeutic strategies beyond conventional antibiotics and antivirals.
- Antimicrobial resistance is a growing threat, limiting the efficacy of existing treatments due to pathogen evolution.
- Host-directed therapies (HDTs) represent an alternative approach by modulating the host's immune response.
Purpose of the Study:
- To review promising and approved HDTs for treating viral and bacterial infections.
- To explore the potential of HDTs in managing diseases across different stages, from acute to chronic.
- To highlight how HDTs can be tailored to specific disease profiles and patient conditions.
Main Methods:
- Literature review of existing and emerging Host-Directed Therapies.
- Analysis of immune system pathways targeted by HDTs.
- Evaluation of HDT efficacy and safety across the disease spectrum.
Main Results:
- HDTs show potential for broad-spectrum activity and adaptability against evolving pathogens.
- Tailoring HDTs to disease profiles (early, chronic, ICU) is crucial for optimal outcomes.
- Advancements in understanding immune function enable precise manipulation for therapeutic benefit.
Conclusions:
- Host-directed therapies offer a flexible and potentially superior alternative to conventional antimicrobials.
- Personalized therapeutic management plans using HDTs can be developed by targeting specific host pathways.
- The benefits of HDTs are expected to surpass their potential side effects as the field advances.
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