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- W4298002146 abstract "Non-alcoholic steatohepatitis (NASH) is a global disease with no effective medication. The fibroblast growth factor 21 (FGF21) can reverse this liver dysfunction, but requires targeted delivery to the liver, which can be achieved via oral administration. Therefore, we fused FGF21 to transferrin (Tf) via a furin cleavage site (F), to promote uptake from the intestine into the portal vein, yielding FGF21-F-Tf, and established its production in both seeds and leaves of commercial Nicotiana tabacum cultivars, compared their expression profile and tested the bioavailability and bioactivity in feeding studies. Since biopharmaceuticals need to be produced in a contained environment, e.g., greenhouses in case of plants, the seed production was increased in this setting from 239 to 380 g m –2 a –1 seed mass with costs of 1.64 € g –1 by side branch induction, whereas leaves yielded 8,193 g m –2 a –1 leave mass at 0.19 € g –1 . FGF21-F-Tf expression in transgenic seeds and leaves yielded 6.7 and 5.6 mg kg –1 intact fusion protein, but also 4.5 and 2.3 mg kg –1 additional Tf degradation products. Removing the furin site and introducing the liver-targeting peptide PLUS doubled accumulation of intact FGF21-transferrin fusion protein when transiently expressed in Nicotiana benthamiana from 0.8 to 1.6 mg kg –1 , whereas truncation of transferrin (nTf338) and reversing the order of FGF21 and nTf338 increased the accumulation to 2.1 mg kg –1 and decreased the degradation products to 7% for nTf338-FGF21-PLUS. Application of partially purified nTf338-FGF21-PLUS to FGF21 –/– mice by oral gavage proved its transfer from the intestine into the blood circulation and acutely affected hepatic mRNA expression. Hence, the medication of NASH via oral delivery of nTf338-FGF21-PLUS containing plants seems possible." @default.
- W4298002146 created "2022-10-01" @default.
- W4298002146 creator A5001547362 @default.
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- W4298002146 creator A5080120118 @default.
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- W4298002146 creator A5085947125 @default.
- W4298002146 date "2022-09-29" @default.
- W4298002146 modified "2023-10-14" @default.
- W4298002146 title "Seed- and leaf-based expression of FGF21-transferrin fusion proteins for oral delivery and treatment of non-alcoholic steatohepatitis" @default.
- W4298002146 cites W1132349362 @default.
- W4298002146 cites W1433606059 @default.
- W4298002146 cites W1901316837 @default.
- W4298002146 cites W1917704618 @default.
- W4298002146 cites W1937016771 @default.
- W4298002146 cites W1968907758 @default.
- W4298002146 cites W1969706853 @default.
- W4298002146 cites W1970142391 @default.
- W4298002146 cites W1971308430 @default.
- W4298002146 cites W1971491811 @default.
- W4298002146 cites W1974062643 @default.
- W4298002146 cites W1977743433 @default.
- W4298002146 cites W1981264193 @default.
- W4298002146 cites W1982261885 @default.
- W4298002146 cites W1982424717 @default.
- W4298002146 cites W1986236572 @default.
- W4298002146 cites W1989584881 @default.
- W4298002146 cites W1990849226 @default.
- W4298002146 cites W1990912748 @default.
- W4298002146 cites W2000368348 @default.
- W4298002146 cites W2000665430 @default.
- W4298002146 cites W2002064053 @default.
- W4298002146 cites W2003377861 @default.
- W4298002146 cites W2004647042 @default.
- W4298002146 cites W2005063766 @default.
- W4298002146 cites W2006024610 @default.
- W4298002146 cites W2007885388 @default.
- W4298002146 cites W2014984130 @default.
- W4298002146 cites W2015936607 @default.
- W4298002146 cites W2016710247 @default.
- W4298002146 cites W2020719323 @default.
- W4298002146 cites W2024209235 @default.
- W4298002146 cites W2025754360 @default.
- W4298002146 cites W2027876836 @default.
- W4298002146 cites W2028358168 @default.
- W4298002146 cites W2029880965 @default.
- W4298002146 cites W2038863889 @default.
- W4298002146 cites W2046739387 @default.
- W4298002146 cites W2055140018 @default.
- W4298002146 cites W2061333499 @default.
- W4298002146 cites W2068830156 @default.
- W4298002146 cites W2072150928 @default.
- W4298002146 cites W2073066276 @default.
- W4298002146 cites W2074189854 @default.
- W4298002146 cites W2077400503 @default.
- W4298002146 cites W2084600650 @default.
- W4298002146 cites W2085379045 @default.
- W4298002146 cites W2095854628 @default.
- W4298002146 cites W2097344008 @default.
- W4298002146 cites W2100436247 @default.
- W4298002146 cites W2102454657 @default.
- W4298002146 cites W2103986567 @default.
- W4298002146 cites W2105493445 @default.
- W4298002146 cites W2108430348 @default.
- W4298002146 cites W2110374590 @default.
- W4298002146 cites W2111426991 @default.
- W4298002146 cites W2111492898 @default.
- W4298002146 cites W2126337135 @default.
- W4298002146 cites W2129168757 @default.
- W4298002146 cites W2131622156 @default.
- W4298002146 cites W2133988967 @default.
- W4298002146 cites W2136769963 @default.
- W4298002146 cites W2143598267 @default.
- W4298002146 cites W2146221143 @default.
- W4298002146 cites W2146544786 @default.
- W4298002146 cites W2148805317 @default.
- W4298002146 cites W2150192230 @default.
- W4298002146 cites W2159652632 @default.
- W4298002146 cites W2165957415 @default.
- W4298002146 cites W2176777883 @default.
- W4298002146 cites W2189310977 @default.
- W4298002146 cites W2232913328 @default.
- W4298002146 cites W2273379493 @default.
- W4298002146 cites W2285066697 @default.
- W4298002146 cites W2292257555 @default.
- W4298002146 cites W2294754341 @default.
- W4298002146 cites W2320334688 @default.
- W4298002146 cites W2340175745 @default.
- W4298002146 cites W2476073495 @default.
- W4298002146 cites W2479108166 @default.
- W4298002146 cites W2516718328 @default.
- W4298002146 cites W2591416052 @default.
- W4298002146 cites W2602116138 @default.
- W4298002146 cites W2615990196 @default.
- W4298002146 cites W2744982526 @default.
- W4298002146 cites W2763362682 @default.
- W4298002146 cites W2767164212 @default.
- W4298002146 cites W2767513058 @default.