Author/Editor		Ravnik-Glavač, M; Glavač, D
Title		Gensko zdravljenje cistične fibroze - napredek in omejitve
Translated title		Gene therapy of cystic fibrosis - progress and limitations
Type		članek
Source		Slov Pediatr
Vol. and No.		Letnik 7, št. Suppl 1
Publication year		2000
Volume		str. 126-31
Language		slo
Abstract		Background. Human gene therapy means the introduction and expression of functional genes in somatic, nonreproductive cells in order to reverse or prevent a particular disorder. Cystic fibrosis (CF) is one of the most common monogenic diseases of white populations which is incurable with currently used therapeutic methods. Because molecular bases of the disease are relatively well determined, cystic fibrosis has become a model disease in studying gene therapy. We describe here the molecular bases of cystic fibrosis, vectors for transfer of therapeutic genes into airways and phase I clinical trials of human gene therapy. Although a lot of studies have been done and great success has been achieved in the last few years, it is not yet possible to cure diseases with gene therapy. Conclusions. New knowledge has raised new questions concerning the complexity in CFTR protein function and heterogeneity of CFTR expression in different lung cell types as well as the limitations connected with various vectors involved in gene transfer. The future gene therapy will probably be in utero gene therapy of embryos with CF. Its progress greatly depends on the development of appropriate animal models, especially the non-human primate CF model for studying the efficiency of gene therapy. Efficient gene therapy will probably not be possible in the near future. However, whenever the knowledge will turn the tide in favor of CF patients, it will bring great hope and relief for thousands of young patients and their parents all over the world.
Summary		Izhodišča. Gensko zdravljenje pri človeku trenutno pomeni vnos in izražanje rekombinantnih normalnih (terapevtskih) genov v prizadete somatske celice z namenom, da bi preprečili napredovanje bolezni ali da bi bolezen celo pozdravili. Ker je cistična fibroza (CF) ena najpogostejših monogenskih bolezeni pri belcih, ki je ni mogoče pozdraviti s sedaj poznanimi metodami, sorazmerno dobro pa so poznane molekularne osnove bolezni, je cistična fibroza postala ena od modelnih bolezni za študij genskega zdravljenja. Na kratko opisujemo molekularne osnove cistične fibroze, vektorje, ki se uporabljajo za vnos terapevtskih genov v dihalne poti, ter klinične poskuse prve faze genskega zdravljenja cistične fibroze pri ljudeh. Kljub številnim raziskavam in napredku, ki je bil narejen na področju genskega zdravljenja cistične fibroze v zadnjih nekaj letih, pa z genskim zdravljenjem bolezni še ni mogoče zdraviti. Zaključki. Nova spoznanja o genskem zdravljenju so odprla številna nova vprašanja, ki so povezana s kompleksno dejavnosti proteina CFTR in njegovo heterogenostjo izražanja v različnih pljučnih celicah, a tudi z omejitvami, ki so povezane z vektorji za prenos genov. Prihodnost genskega zdravljenja bo verjetno v genskem zdravljenju zarodkov s CF in utero. Njen razvoj pa je znatno odvisen od razvoja primernih živalskih modelov za študij uspešnosti genskega zdravljenja, predvsem opičjega modela CF. Uspešnega genskega zdravljenja verjetno še ne bo mogoče doseči v bližnji prihodnosti. Kadarkoli pa se bo val o genskem zdravljenju preobrnil v prid bolnikov s CF, bo prinesel s seboj veliko upanje in olajšanje za tisoče mladih bolnikov in njihovih staršev po svetu.
Descriptors		CYSTIC FIBROSIS GENE THERAPY CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENETIC VECTORS