Genska terapija u liječenju lizosomskih bolesti

undergraduate thesis

• Title (english): Gene therapy for lysosomal diseases
• Author: Lucija Botica
• Mentor: Petra Korać (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-07-24, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Lizosomske bolesti su rijetke nasljedne bolesti koje se pojavljuju u 1 od 5000 rođenja. Karakterizirane su mutacijom u specifičnom genu koji kodira protein potreban za pravilan rad lizosoma. Rezultiraju akumulacijom određenog supstrata u lizosomima i tako uzrokuju različite simptome koji zahvaćaju više organskih sustava. Dosadašnji pristupi liječenju uključuju terapiju zamjenskim enzimima, terapiju malim molekulskim šaperonima, terapiju smanjenja količine supstrata i transplantaciju hematopoetskih matičnih stanica. Nova otkrića u genskoj terapiji zaobilaze ograničenja dosadašnjih terapija poput česte readministracije, slabe efikasnosti i prolaska kroz krvno-moždanu barijeru. Danas se intenzivno istražuju pristupi ex vivo i in vivo s integrativnim i neintegrirajućim virusnim vektorima kako bi se izbjegle poteškoće poput poticanja imunosnog odgovora i insercijske mutagenze te kako bi se unaprijedilo ciljanje specifičnih tkiva. U budućnosti bi istraživanje mehanizama genske terapije na primjeru lizosomskih bolesti moglo biti temelj liječenja raznih drugih nasljednih genetskih poremećaja.

Abstract (english)

Lysosomal diseases are rare inherited disorders that occur in 1 of 5000 births. They are characterized by a mutation in a single gene coding a protein necessary for the normal functioning of lysosomes. They result in the accumulation of specific substrates within the lysosome, causing various symptoms that affect multiple organ systems. Current treatment approaches include enzyme replacement therapy, therapy with small molecular chaperones, substrate reduction therapy, and hematopoietic stem cell transplantation. New discoveries in gene therapy bypass the barriers of previous therapies such as frequent readministration, low effectiveness, and crossing the blood-brain barrier. Currently, ex vivo and in vivo approaches with integrative and non-integrative viral vectors are being intensively researched to minimize risks such as immune response and insertional mutagenesis and to improve targeting of specific tissues. In the future, investigating the mechanisms of gene therapy using lysosomal diseases as an example could be a milestone in treating various other inherited genetic disorders.

• Keywords: virus povezan s adenovirusom; lentivirus; klinička istraživanja; insercijska mutageneza; uređivanje gena
• Keywords (english): adeno-associated virus; lentivirus; clinical trials; insertional mutagenesis; gene editing
• Language: croatian
• URN:NBN: urn:nbn:hr:217:731133
• Study programme: Title: Molecular biology-University undergraduate programme; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-09-03 12:22:40