Korištenje virusa AAV u genskoj terapiji

undergraduate thesis

• Title (english): Use of virus AAV in gene therapy
• Author: Ante Mrkonjić
• Mentor: Petra Korać (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-07-09, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Virus povezan s adenovirusima (AAV, od engl. adeno-associated virus) je virus koji je čest u ljudskoj populaciji, velike je bioraznolikosti te se ne smatra uzročnikom bolesti. Danas je često korišten u genskoj terapiji kao vektor zbog jednostavne kontrole njegove replikacije, dugotrajne ekspresije u stanicama te nedostatka patogenosti. Jedna od osnovnih karakteristika mu je i podložnost doradi genoma te mogućnost pakiranja viriona unatoč izbacivanju većeg dijela gena divljeg tipa virusa AAV i zamjeni tih gena za transgen. U sklopu dorade genoma koriste se i različite modifikacije kojim se poboljšava kontrola ekspresije trangena kroz promjenu intenziteta ekspresije i promjenu specifičnosti ekspresije. Kontrola ekspresije često se postiže mijenjanjem promotora i drugih regulacijskih elemenata. Genom se često mijenja i zbog ograničenosti veličine inserta. Taj se problem savladava korištenjem manjih verzija funkcionalnih transgena i strategijom dvojnih vektora. Nadalje, modifikacije kapside ovog vektora čest su predmet istraživanja jer mogu dovesti do specifičnog tropizma vektora i time učiniti gensku terapiju preciznijom. Dorade kapsidnih proteina rade se i radi smanjenja imunosnog odgovora pri administraciji genske terapije te se pomoću njih nastoji izbjeći prepoznavanje vektora antitijelima i citotoksičnim limfocitima T. Zbog navedenih, ali i nekih drugih modifikacija virusa, ovaj je vektor danas često dio genskih terapija i temelj terapija koje su u kliničkim istraživanjima. Generalno, pogodna priroda virusa AAV i brojne intervencije kojima se virus izlaže mogle bi osigurati dominaciju vektora AAV u području virusnih vektora.

Abstract (english)

Adeno-associated virus (AAV) is a virus commonly found in human population, which exhibits great biodiversity and is not considered a cause of disease. Nowadays, it is often used in gene therapy, as a vector, due to the simplicity of controlling its replication, its long-term expression in cells, and its lack of pathogenicity. One of its main characteristics is the susceptibility to modification of its genome and the ability to package virions, despite removal of a significant portion of the wild-type AAV genes and their replacement with transgenes. Various modifications are used in genome editing to improve the control of transgene expression through adjusting the intensity and specificity of expression. Expression control is often achieved by altering promoters and other regulatory elements. The genome is frequently modified because of the size limitations of the insert. This problem is solved by using smaller versions of functional transgenes and a dual vector strategy. Furthermore, capsid modifications of this vector are a common subject of research as they can lead to specific vector tropism and, consequently, make gene therapy more precise. Capsid protein adjustments are also made to reduce immune response during gene therapy administration, aiming to avoid vector recognition by antibodies and cytotoxic T lymphocytes. Due to these, and some other modifications of the virus, this vector is nowadays often part of gene therapies and forms the basis of therapies that are currently in clinical trials. Generally, the favorable nature of AAV virus and many interventions it undergoes could ensure the supremacy of AAV vectors in the field of viral vectors.

• Keywords: vektor; modifikacije; transgen; serotip; ekspresija
• Keywords (english): vector; modifications; transgene; serotype; expression
• Language: croatian
• URN:NBN: urn:nbn:hr:217:021428
• 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 12:37:58