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
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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. / Dubois, A E J; Pagliarani, G; Brouwer, R M; Kollen, B J; Dragsted, Lars Ove; 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.
In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 70, No. 11, 2015, p. 1406-1412.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - First successful reduction of clinical allergenicity of food by genetic modification
T2 - Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar
AU - Dubois, A E J
AU - Pagliarani, G
AU - Brouwer, R M
AU - Kollen, B J
AU - Dragsted, Lars Ove
AU - Eriksen, F D
AU - Callesen, O
AU - Gilissen, L J W J
AU - Krens, F A
AU - Visser, R G F
AU - Smulders, M J M
AU - Vlieg-Boerstra, B J
AU - Flokstra-de Blok, B J
AU - van de Weg, W E
N1 - CURIS 2015 NEXS 266
PY - 2015
Y1 - 2015
N2 - BACKGROUND: 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.METHODS: 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, by RNA interference. Downregulation of Mal d 1 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).RESULTS: Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 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 vs 0.0 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm vs 0.2 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 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.CONCLUSION: These data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 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.
AB - BACKGROUND: 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.METHODS: 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, by RNA interference. Downregulation of Mal d 1 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).RESULTS: Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 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 vs 0.0 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm vs 0.2 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 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.CONCLUSION: These data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 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.
U2 - 10.1111/all.12684
DO - 10.1111/all.12684
M3 - Journal article
C2 - 26138410
VL - 70
SP - 1406
EP - 1412
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
SN - 0105-4538
IS - 11
ER -
ID: 142036689