SBIR Phase II: Development of An Allergen-Free Peanut Using Genome Editing Technology

SBIR 第二阶段：利用基因组编辑技术开发无过敏原花生

• 批准号: 2036153
• 负责人: Hortense Dodo
• 金额: $ 99.67万
• 依托单位: IngateyGen LLC
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2036153&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Development; Allergen

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to address health concerns associated with peanut allergies. Peanut allergies affect a large population and can be extremely dangerous for those with the most severe forms. Given the ubiquity of peanut products, peanut allergy is a significant medical and legal concern worldwide, with a rising incidence of this potentially fatal condition in children. An allergen-free peanut developed from this project has the potential to significantly dampen the life-threatening reactions to peanuts, as well as the following benefits: (1) reducing the overall incidence of food allergy, (2) preserving human lives by eliminating anaphylaxis and death caused by accidental ingestion of peanut, (3) eliminating emotional distress of peanut allergic individuals and their families, (4) enhancing the public perception of peanuts as a health-promoting food, and (5) reducing the number of product recalls due to peanut contamination. The proposed project aims to develop and to commercialize an allergen-free peanut devoid of all clinically documented allergens using a genome-editing tool such as CRISPR/Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated system). Allergic reactions to peanut occur shortly after contact of peanut allergens with their specific IgE antibodies already bound to mast cells. The crosslinking of allergen specific IgE by the respective peanut allergens stimulates mast cells to release chemical mediators responsible for the clinical symptoms including sometime anaphylactic shock or death. Ara h 1, Ara h 2, Ara h 3 and Ara h 6 are the most clinically documented peanut allergens. The objectives of the project are: (1) Construct and validate vectors for Ara h gene editing, transform peanut embryogenic callus and regenerate T0 peanut plants; (2) Identify T0 individuals with deletions in Ara h genes; (3) Assemble lines carrying homozygous deletions in all target Ara h genes; (5) Characterize the selected lines for Ara h mRNA and protein expression; (6) Assess vegetative development of Arah-free lines under greenhouse conditions. If the resulting plants demonstrate tolerance to the gene deletions, the allergen-free peanut will be very significant in protecting the peanut sensitive populations and promoting peanut sales.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业创新研究（SBIR）第二阶段项目的更广泛影响是解决与花生过敏相关的健康问题。花生过敏影响了大量人口，对于那些最严重的人来说可能非常危险。鉴于花生产品的普遍存在，花生过敏是一个重要的医学和法律的问题，在世界范围内，随着这种潜在的致命疾病在儿童中的发病率不断上升。 从该项目开发的无过敏原花生有可能显着抑制对花生的危及生命的反应，以及以下好处：（1）降低食物过敏的总发生率，（2）通过消除由意外摄入花生引起的过敏反应和死亡来保护人的生命，（3）消除花生过敏个体及其家庭的情绪困扰，（4）加强公众对花生作为促进健康食物的认知;及（5）减少因花生受污染而须回收的产品数目。 该项目旨在开发和商业化一种不含过敏原的花生，该花生不含所有临床记录的过敏原，使用基因组编辑工具，如CRISPR/Cas（定期间隔的短回文重复序列和CRISPR相关系统）。花生过敏反应发生后不久，花生过敏原与他们的特异性IgE抗体已经结合到肥大细胞。过敏原特异性IgE通过各自的花生过敏原的交联刺激肥大细胞释放化学介质，所述化学介质导致临床症状，有时包括过敏性休克或死亡。Ara h 1、Ara h 2、Ara h 3和Ara h 6是临床记录最多的花生过敏原。该项目的目标是：（1）构建和验证Ara h基因编辑载体，转化花生胚性愈伤组织并再生T0花生植株;（2）鉴定Ara h基因缺失的T0个体;（3）组装所有靶Ara h基因纯合缺失的品系;（5）表征所选品系的Ara h mRNA和蛋白表达;（6）鉴定所选品系的Ara h基因。（6）评估温室条件下无Arah品系的营养发育。如果培育出的花生能够耐受基因缺失，那么这种无过敏原的花生将对保护花生敏感人群和促进花生销售具有非常重要的意义。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。