Abstract
ABSTRACT Viruses have evolved to efficiently express their genes in host cells, which makes them ideally suited as gene delivery vectors for gene and immunotherapies. Replication competent (RC) viral vectors encoding foreign or self-proteins induce strong T-cell responses that can be used for the development of effective cancer treatments. Replication-defective (RD) viral vectors encoding self-proteins are non-immunogenic when introduced in a host naïve for the cognate virus. RD viral vectors can be used to develop gene replacement therapies for genetic disorders and tolerization therapies for autoimmune diseases and allergies. Degenerative/inflammatory diseases are associated with chronic inflammation and immune responses that damage the tissues involved. These diseases therefore strongly resemble autoimmune diseases. This review deals with the use of RC and RD viral vectors for unraveling the pathogenesis of immune-related diseases and their application to the development of the next generation prophylactics and therapeutics for todays’ major diseases.
Highlights
Viruses have evolved to efficiently express their genes in host cells, which makes them ideally suited as gene delivery vectors for gene and immunotherapies
Cells of the innate immune system are activated by pathogen-associated molecular patterns (PAMPs) released from infected cells or damageassociated molecular patterns (DAMPs) released from malignant or wounded cells
When PAMPs or DAMPs are registered by innate immunity cells, inflammasomes assemble in the cytoplasm and a local inflammatory response is initiated.[1]
Summary
Viruses have evolved to efficiently express their genes in host cells, which makes them ideally suited as gene delivery vectors for gene and immunotherapies. The immune responses lead to elimination of the transduced cells from the body and decreasing expression levels of the therapeutic transgenes over time, compromising re-administration of the vector.[33] AAV’s immunogenicity in humans, and as a result its clinical inefficacy, will remain the major challenge for the development and approval of new AAV vector-based interventions.
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