Gene Therapy for Graft-versus-Host-Disease
Genová terapie reakce štěpu proti hostiteli
Reakce štěpu proti hostiteli (GVHD) je častou a obávanou komplikací allogenních transplantací kostní dřeně. Genováterapie nabízí možnost, jak se s ní vyrovnat. Jde o zavedení tzv. sebevražedných genů (SG) do dárcovských lymfocytůT, které jsou zodpovědné za vznik GVHD. Propukne-li GVHD, je možné dárcovské buňky T eliminovat s dodánímsubstance, kterou produkt SG přemění ve vysoce cytotoxický metabolit. Běžně používaným vektorem pro přenosSG jsou geneticky upravené retroviry. Autoři se pokusili nahradit je rekombinantními adeno-asociovanými viry(AAV). Pokus byl neúspěšný. Účinnost transdukce byla velmi nízká. Jak ukázaly další pokusy, příčinou je chyběníreceptoru pro AAV na lymfocytech T. Pokud se nepodaří dalšími modifikacemi upravit povrch AAV tak, aby snadnovstupovaly do tohoto typu buněk, nebude možné jimi nahradit současně používané retrovirové vektory.
Klíčová slova:
genová terapie, GVHD, AAV.
Authors:
O. Janoušková; I. Fales; P. Kobylka; V. Vonka
Authors‘ workplace:
Ústav hematologie a krevní transfuze, Praha
Published in:
Čas. Lék. čes. 2003; : 530-533
Category:
Overview
Graft-versus-host-disease (GVHD) is a frequent and dangerous complication of allogenic transplantations of bonemarrow. Gene therapy offers a way to deal with the problem. It is based on the introduction of suicide genes (SG)into the donor´s Tl ymphocytes, which are responsible for the development of GVHD. If it develops, the presenceof SG in the effector cells gives an opportunity to get rid of them, because their products are capable of changingotherwise innocuous substances into highly cytotoxic metabolites. For the transduction of SG retrovirus-based vectorsare used. The authors tried to employ for this purpose recombinant adeno-associated viruses (rAAV). The attemptwas unsuccessful. When using rAAV as vectors, the efficacy of transduction was very low. Further experimentsindicated that this failure was dueto the absence ofreceptor for AAV in Tlymphocytes. It seems clear that until thesurface of rAAV is modified to facilitate their penetration into Tc ells, they cannot replace retroviruses for transferof SG into this cell type.
Key words:
gene therapy, GVHD, AAV.
Labels
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistArticle was published in
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