New Frontiers: Precise Editing of Allergen Genes Using CRISPR

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) technology offers the unique potential for unequivocally deleting allergen genes at the source. Compared to prior gene editing approaches, CRISPR boasts substantial improvements in editing efficiency, throughput, and precision. CRISPR has demonstrated success in several clinical applications such as sickle cell disease and β-thalassemia, and preliminary knockout studies of allergenic proteins using CRISPR editing show promise. Given the advantages of CRISPR, as well as specific DNA targets in the allergen genes, CRISPR gene editing is a viable approach for tackling allergy, which may lead to significant disease improvement. This review will highlight recent applications of CRISPR editing of allergens, particularly cat allergen Fel d 1, and will discuss the advantages and limitations of this approach compared to existing treatment options.

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The Major Cat Allergen, Fel d 1, Is a Viable Target for CRISPR Gene Editing.

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2020.12.617 ◽

2021 ◽

Vol 147 (2) ◽

pp. AB175

Author(s):

Nicole Brackett ◽

Anna Pomes ◽

Martin Chapman

Keyword(s):

Gene Editing ◽

Fel D 1 ◽

Cat Allergen

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Gene Editing the Major Cat Allergen, Fel d 1, Using CRISPR-Cas9

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2019.12.405 ◽

2020 ◽

Vol 145 (2) ◽

pp. AB156

Author(s):

Nicole Brackett ◽

Julia Riedy ◽

Mazhar Adli ◽

Anna Pomes ◽

Martin Chapman

Keyword(s):

Gene Editing ◽

Fel D 1 ◽

Cat Allergen

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An overview of allergens

Allergy and Asthma Proceedings ◽

10.2500/aap.2019.40.4247 ◽

2019 ◽

Vol 40 (6) ◽

pp. 362-365

Author(s):

Dawn K. Lei ◽

Leslie C. Grammer

Keyword(s):

Molecular Weight ◽

Fungal Spores ◽

Allergic Response ◽

House Dust Mites ◽

Ocular Symptoms ◽

Fel D 1 ◽

Allergenic Proteins ◽

Cat Allergen ◽

Route Of Exposure ◽

Can F 1

Most allergens are proteins or glycoproteins that range in molecular weight from 5000 to 100,000 Da, although polysaccharides and low-molecular-weight substances may also be allergenic. Common allergens include pollens, fungal spores, house-dust mites, and animal epithelial materials but can also include drugs, biologic products, and insect venoms. The allergic response is dependent on the route of exposure. If the exposure is to an inhaled aeroallergen, then the allergic response will be respiratory in nature. Ingested or injected exposure gives rise to gastrointestinal, cutaneous, or anaphylactic reactions. The size of the pollen determines the clinical manifestation of allergy. For example, particles between 20 and 60 μm in diameter can be carried by the wind and cause nasal and ocular symptoms (allergic rhinoconjunctivitis). Particles of <7 μm can deposit in the airways and cause symptoms of asthma. Animals produce allergens in forms unique to each species. Cat allergen, most importantly Fel d 1, is buoyant and “sticky,” which means it easily remains airborne and may last in a home for up to 6 to 9 months after the source is removed. Cat allergen adheres to clothes and can be found in public places, e.g., schools. Dog allergen, particularly Can f 1, is present in dander, saliva, urine, and serum. All dog breeds produce allergenic proteins (even poodles and “hairless” dogs).

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The Calcium Goes Meow: Effects of Ions and Glycosylation on Fel d 1, the Major Cat Allergen

PLoS ONE ◽

10.1371/journal.pone.0132311 ◽

2015 ◽

Vol 10 (7) ◽

pp. e0132311 ◽

Cited By ~ 10

Author(s):

Rodrigo Ligabue-Braun ◽

Liana Guimarães Sachett ◽

Laércio Pol-Fachin ◽

Hugo Verli

Keyword(s):

Fel D 1 ◽

Cat Allergen

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Bevacizumab plus capecitabine as later-line treatment for patients with metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines

Scientific Reports ◽

10.1038/s41598-021-86482-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yeong Hak Bang ◽

Jeong Eun Kim ◽

Ji Sung Lee ◽

Sun Young Kim ◽

Kyu-Pyo Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Median Overall Survival ◽

Treatment Options ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Line Treatment ◽

Free Survival ◽

Medical Need ◽

Significant Disease

AbstractThere is an unmet medical need for later-line treatment options for patients with metastatic colorectal cancer (mCRC). Considering that, beyond progression, co-treatment with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate, we aimed to evaluate the efficacy of capecitabine and bevacizumab. This single-center retrospective study included 157 patients between May 2011 and February 2018, who received bevacizumab plus capecitabine as later-line chemotherapy after progressing with irinotecan, oxaliplatin, and fluoropyrimidines. The study treatment consisted of bevacizumab 7.5 mg/kg on day 1 and capecitabine 1,250 mg/m2 orally (PO) twice daily on day 1 to 14, repeated every 3 weeks. The primary endpoint was progression-free survival (PFS). The median PFS was 4.6 months (95% confidence interval [CI] 3.9–5.3). The median overall survival (OS) was 9.7 months (95% CI 8.3–11.1). The overall response rate was 14% (22/157). Patients who had not received prior targeted agents showed better survival outcomes in the multivariable analysis of OS (hazard ratio [HR] = 0.59, 95% CI 0.43–0.82, P = 0.002) and PFS (HR = 0.61, 95% CI 0.43–0.85, P = 0.004). Bevacizumab plus capecitabine could be a considerably efficacious option for patients with mCRC refractory to prior standard treatments.

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