The recent approval by regulatory agencies for the treatment of sickle cell disease and transfusion-dependent B-thalassemia heralds a new beginning for gene editing in clinical medicine, potentially extending to the treatment of a wide array of allergic diseases. In just barely a decade, science has moved the conversion of the clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 bacterial immune system into a programmable gene editing nuclease. The CRISPR gene editing technology has been employed with precision to generate gene knockouts, alter genes, and to identify genes that cause disease. Although initially used to edit and repair disease-associated mutations, this technology and newer approaches have been central in identifying novel molecular pathways and therapeutic targets. The goals of gene therapy are to introduce, modify or replace culprit genes in cells. Cell types such as CD4+ T cells, dendritic cells, mediators and Th2 cytokines play critical roles in disease pathology. Many of the allergic/atopic diseases share this common cytokine -directed immunopathology. Targeting sentinel genes in these cells and proteins individually or targeting multiple genes with gene editing tools such as CRISPR-Cas9 has already improved our understanding of the mechanisms underlying the allergic diseases. This platform has advanced our knowledge and fostered the introduction of many effective targeted biologics, but none are completely effective, durable, curative or without safety issues. Thus, for all the atopic conditions, significant unmet needs persist.
Importantly, gene modification may not be restricted to pluripotent stem cells. Gene repair of autologous T cells is a novel, promising treatment for some human diseases such as familial hemophagocytic lymphohistiocytosis. Gene repair has been used effectively in angioedema patients. A single infusion of an in vivo gene editing therapy based on CRISPR-Cas9 targeting of the gene encoding kaliikrein B1 resulted in robust durable reductions in total plasma kallikrein levels and in the number of angioedema attacks. In peanut allergy and asthma, we identified a novel and pivotal role for CYP11A1using in vitro cell models, in vivo animal models and cells from patients themselves using gene silencing and CRISPR-Cas9.
Newer approaches to gene editing are now being introduced to limit off-target effects and to enhance efficient delivery. The advances today and the progress suggest that the allergic diseases are ripe for targeting. As implementation of immunotherapy for allergic diseases increases, much attention has focused on manipulation of causative allergens through gene editing. The overarching goal is to delete allergenic genes decreasing allergies and to minimize allergenicity.
The aims of this Research Topic are to highlight advances in gene editing, promote collaborative interactions, and describe the latest data where gene editing has impacted our understanding of specific or generalities of allergic disease and modification of allergenicity. In this way, identification of novel molecular pathways and potential therapeutic advances will ensue.
Areas to be covered on gene editing may include but are not limited to:
- altering the immunopathology of any or some atopic disease
- further explain the complex interaction of genetic, epigenetic and environmental factors
- identification of novel and critical molecular events
- feasibility of targeting peripheral blood Th2 cells
- pre-clinical and clinical applications of gene editing
- further understanding the role of mutations of unknown significance
- modify SNPs that contribute to allergic disease
- novel advances in gene editing
- explaining the heterogeneous nature of the atopic diseases
- feasibility of targeting animal and plant allergenicity to produce hypoallergenic animals and foods
We welcome authors to submit Original Research, Reviews and Case Reports focusing on how gene editing and gene modification will inform and change current thinking of atopic disease
Keywords:
gene therapy; CRISPR-Cas9; immunopathology; gene editing
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
The recent approval by regulatory agencies for the treatment of sickle cell disease and transfusion-dependent B-thalassemia heralds a new beginning for gene editing in clinical medicine, potentially extending to the treatment of a wide array of allergic diseases. In just barely a decade, science has moved the conversion of the clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 bacterial immune system into a programmable gene editing nuclease. The CRISPR gene editing technology has been employed with precision to generate gene knockouts, alter genes, and to identify genes that cause disease. Although initially used to edit and repair disease-associated mutations, this technology and newer approaches have been central in identifying novel molecular pathways and therapeutic targets. The goals of gene therapy are to introduce, modify or replace culprit genes in cells. Cell types such as CD4+ T cells, dendritic cells, mediators and Th2 cytokines play critical roles in disease pathology. Many of the allergic/atopic diseases share this common cytokine -directed immunopathology. Targeting sentinel genes in these cells and proteins individually or targeting multiple genes with gene editing tools such as CRISPR-Cas9 has already improved our understanding of the mechanisms underlying the allergic diseases. This platform has advanced our knowledge and fostered the introduction of many effective targeted biologics, but none are completely effective, durable, curative or without safety issues. Thus, for all the atopic conditions, significant unmet needs persist.
Importantly, gene modification may not be restricted to pluripotent stem cells. Gene repair of autologous T cells is a novel, promising treatment for some human diseases such as familial hemophagocytic lymphohistiocytosis. Gene repair has been used effectively in angioedema patients. A single infusion of an in vivo gene editing therapy based on CRISPR-Cas9 targeting of the gene encoding kaliikrein B1 resulted in robust durable reductions in total plasma kallikrein levels and in the number of angioedema attacks. In peanut allergy and asthma, we identified a novel and pivotal role for CYP11A1using in vitro cell models, in vivo animal models and cells from patients themselves using gene silencing and CRISPR-Cas9.
Newer approaches to gene editing are now being introduced to limit off-target effects and to enhance efficient delivery. The advances today and the progress suggest that the allergic diseases are ripe for targeting. As implementation of immunotherapy for allergic diseases increases, much attention has focused on manipulation of causative allergens through gene editing. The overarching goal is to delete allergenic genes decreasing allergies and to minimize allergenicity.
The aims of this Research Topic are to highlight advances in gene editing, promote collaborative interactions, and describe the latest data where gene editing has impacted our understanding of specific or generalities of allergic disease and modification of allergenicity. In this way, identification of novel molecular pathways and potential therapeutic advances will ensue.
Areas to be covered on gene editing may include but are not limited to:
- altering the immunopathology of any or some atopic disease
- further explain the complex interaction of genetic, epigenetic and environmental factors
- identification of novel and critical molecular events
- feasibility of targeting peripheral blood Th2 cells
- pre-clinical and clinical applications of gene editing
- further understanding the role of mutations of unknown significance
- modify SNPs that contribute to allergic disease
- novel advances in gene editing
- explaining the heterogeneous nature of the atopic diseases
- feasibility of targeting animal and plant allergenicity to produce hypoallergenic animals and foods
We welcome authors to submit Original Research, Reviews and Case Reports focusing on how gene editing and gene modification will inform and change current thinking of atopic disease
Keywords:
gene therapy; CRISPR-Cas9; immunopathology; gene editing
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.