Advances in Clinical and Experimental Medicine

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Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 4, July-August, p. 525–534

Publication type: review article

Language: English

Gene Therapy Prospects – Intranasal Delivery of Therapeutic Genes

Perspektywy terapii genowej – donosowe podawanie terapeutycznych genów

Karolina Podolska1,, Anna Stachurska1,2,, Karolina Hajdukiewicz1,2,, Maciej Małecki1,2,

1 Department of Cell Biology, Cancer Center, Warsaw, Poland

2 Department of Molecular Biology, Medical University of Warsaw, Poland

Abstract

Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

Streszczenie

Terapia genowa jest nową metodą leczenia chorób. Strategia terapii genowej opiera się na wykorzystaniu do celów terapeutycznych genów kodujących białka o kluczowym znaczeniu dla przebiegu procesów biologicznych warunkujących powstawanie i rozwój chorób. Obecnie próby kliniczne terapii genowej dotyczą głównie nowotworów, zaburzeń sercowo-naczyniowych i chorób zakaźnych. Skuteczność kliniczna terapii genowej wiąże się bezpośrednio z opracowywaniem metod wprowadzania genów do wybranych komórek, narządów. Terapeutyczne geny są dostarczane do tkanek za pomocą nośników – wektorów. Retrowirusy, adenowirusy i wirusy związane z adenowirusami są najczęściej stosowanymi wektorami terapii genowej w klinice. Dotychczas preparaty genowe mogą być podawane dożylnie, domięśniowo, dojamowo, doguzowo oraz donosowo. Skuteczność terapeutyczna genów, terapii genowej jest bezpośrednio związana z ekspresją transgenów w docelowych komórkach. Zarówno zakłady badań podstawowych, jak i kliniki nie dysponują jeszcze optymalnymi wektorami, metodami wprowadzania genów do chorych narządów. Wiele grup badawczych prowadzi badania poświęcone udoskonalaniu istniejących i poszukiwaniu nowych metod wprowadzania terapeutycznych genów do komórek. Pomysł wprowadzania terapeutycznych genów przez nos jest bardzo interesujący głównie z uwagi na olbrzymią aplikacyjność kliniczną. Donosowe dostarczanie terapeutycznych genów jest uważane za jedną z najbardziej obiecujących – bezpiecznych i skutecznych metod w terapii genowej chorób płuc. Terapia genowa wykorzystująca preparaty genowe wprowadzane przez nos pozwala podejmować próby leczenia pacjentów cierpiących np. na mukowiscydozę, defekt alfa-1-antytrypsyny lub nowotwory. Badania eksperymentalne i pierwsze próby kliniczne przeprowadzone z wektorami plazmidowymi lub rekombinowanymi wirusami wykazały, że stosowane wektory mogą wydajnie dostarczać terapeutyczne geny do komórek układu oddechowego. Wykorzystanie donosowej, nieinwazyjnej drogi podawania preparatów genowych lub konwencjonalnych leków budzi entuzjazm wśród naukowców i pacjentów. Dalsze badania określą bezpośrednią użyteczność i dostępność donosowych preparatów genowych w klinice.

Key words

gene preparations, gene therapy, inhalation, cystic fibrosis, alpha-1-antitrypsin deficiency, lung cancer

Słowa kluczowe

preparaty genowe, terapia genowa, wdychanie, mukowiscydoza, defekt alfa-1-antytrypsyny, rak płuc

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