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The Ras-GAP neurofibromin is a very large cytoplasmic protein (2818 AA, 319\u2009kDa) involved in the RAS-MAPK pathway. Aside from regulation of proliferation, it is involved in mechanosensoric of cells. We investigated neurofibromin replacement in cultured human fibroblasts showing reduced amount of neurofibromin. Full length neurofibromin was produced recombinantly in insect cells and purified. Protein transduction into cultured fibroblasts was performed employing cell penetrating peptides along with photochemical internalization. This combination of transduction strategies ensures the intracellular uptake and the translocation to the cytoplasm of neurofibromin. The transduced neurofibromin is functional, indicated by functional rescue of reduced mechanosensoric blindness and reduced RasGAP activity in cultured fibroblasts of NF1 patients or normal fibroblasts treated by NF1 siRNA. Our study shows that recombinant neurofibromin is able to revert cellular effects of <jats:italic>NF1<\/jats:italic> haploinsuffiency <jats:italic>in vitro<\/jats:italic>, indicating a use of protein transduction into cells as a potential treatment strategy for the monogenic disease NF1.<\/jats:p>","DOI":"10.1038\/s41598-018-24310-5","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T10:57:09Z","timestamp":1523530629000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Restoring functional neurofibromin by protein transduction"],"prefix":"10.1038","volume":"8","author":[{"given":"K.","family":"Mellert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Lechner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"L\u00fcdeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lamla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"M\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Kemkemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Scheffzek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,18]]},"reference":[{"key":"24310_CR1","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/S1474-4422(07)70075-3","volume":"6","author":"RE Ferner","year":"2007","unstructured":"Ferner, R. 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