First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1‐silenced apples cause fewer allergy symptoms than the wild‐type cultivar. Issue 11 (24th July 2015)

• Record Type: Journal Article
• Authors: Dubois, A. E. J.; Pagliarani, G.; Brouwer, R. M.; Kollen, B. J.; Dragsted, L. O.; Eriksen, F. D.; Callesen, O.; Gilissen, L. J. W. J.; Krens, F. A.; Visser, R. G. F.; Smulders, M. J. M.; Vlieg‐Boerstra, B. J.; Flokstra‐de Blok, B. J.; van de Weg, W. E.
• Is Part Of: Allergy. Volume 70:Issue 11(2015:Nov.)
• Page Start: 1406
• Page End: 1412
• Publication Date: 2015-07-24
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12684
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12684-abs-0001"> <title>Abstract</title> <sec id="all12684-sec-0001" sec-type="section"> <title>Background</title> <p>Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals.</p> </sec> <sec id="all12684-sec-0002" sec-type="section"> <title>Methods</title> <p>We performed oral food challenges in 21 apple‐allergic individuals with Elstar apples which had undergone gene silencing of the major allergen of apple, Mal d 1<italic>, </italic> by RNA interference. Downregulation of <italic>Mal d 1</italic> gene expression in the apples was verified by qRT‐PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild‐type Elstar using a visual analogue scale (VAS).</p> </sec> <sec id="all12684-sec-0003" sec-type="section"> <title>Results</title> <p>Gene silencing produced two genetically modified apple lines expressing <italic>Mal d 1.02</italic> and other <italic>Mal d 1</italic> gene mRNA levels which were extensively downregulated, that is only 0.1–16.4% (e‐DR1) and 0.2–9.9% (e‐DR2) of those of the wild‐type Elstar, respectively. Challenges with these downregulated apple lines produced significantly less intense maximal symptoms to the first dose (Vmax1) than with Elstar (Vmax1 Elstar 3.0 mm <italic>vs</italic> 0.0 mm for e‐DR1, <italic>P</italic> = 0.017 and 0.0 mm for e‐DR2, <italic>P</italic> = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm <italic>vs</italic> 0.2 mm for e‐DR1, <italic>P</italic> = 0.017 and 0.0 mm for e‐DR2, <italic>P</italic> = 0.043). Only one subject (5%) remained symptom‐free when challenged with the Elstar apple, whereas 43% did so with e‐DR1 and 63% with e‐DR2.</p> </sec> <sec id="all12684-sec-0004" sec-type="section"> <title>Conclusion</title> <p>These data show that mRNA silencing of <italic>Mal d 1</italic> results in a marked reduction of <italic>Mal d 1</italic> gene expression in the fruit and reduction of symptoms when these apples are ingested by allergic subjects. Approximately half of the subjects developed no symptoms whatsoever, and virtually all subjects wished to consume the apple again in the future.</p> </sec> </abstract>