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Gensko zdravljenje
GENE THERAPY – GENSKO ZDRAVLJENJE
• Substitucija
• Adicija
GENSKO ZDRAVLJENJE
• Somatsko gensko zdravljenje
• Zarodno gensko zdravljenje
GENSKO ZDRAVLJENJE
• Fizikalni vnos
• Kemijsko-fizikalni vnos
• Biološki vnos
Table 1. Summary of in vivo gene delivery systems.
Viral Method Non Viral Methods
Viruses
serving as
viral vectors:
Retroviruses
Adenoviruses
Adeno-
associated
viruses
Herpes
simplex
viruses
Lenti virus
Micro Seeding
Gene Therapy:
Direct injection of therapeutic DNA into target cells using a gene gun. This
approach is limited in its application because it can be used only with certain
tissues and requires large amounts of DNA (simplest method).
Cationic
Liposomes:
Creation of artificial lipid spheres with an aqueous core. This liposome, which
carries the therapeutic DNA, is capable of passing the DNA through the target
cell's membrane.
Macromolecul
ar Conjugate:
Here therapeutic DNA gets inside target cells by chemically linking the DNA to a
molecule that will bind to special cell receptors. Once bound to these receptors,
the therapeutic DNA constructs are engulfed by the cell membrane and passed
into the interior of the target cell. This delivery system tends to be less effective
than other options.
Gene
Activated
Matrices
(GAMS):
These deliver naked DNA via polymer matrix sponges.
Gensko zdravljene z uporabo virusnega vektorja
Gene delivery
system Advantages Disadvantages
Retrovirus
integrates into host cell
genome providing stable
gene expression
random integration may cause
insertional mutations
Adenovirus contains >30 kb of non-
viral DNA, infects non-
dividing and dividing
cells
does not provide long term gene
expression; no integration
Adeno-
associated
virus
contains no viral genes,
non-pathogenic, no
immunity problems
small capacity for gene
sequences, difficult to obtain
large viral stocks
Liposomes non-pathogenic, no
immunity problems, no
limit to size of gene
low transfection efficiency, low
rate of stable integration
Biolistics same as liposome-
mediated transfer,
promising as a
vaccination method
limited to dermal tissue, low rate
of stable integration, difficult to
QC
Disease Target cells Transfected gene(s)
Hemophilia A
Hemophilia B
liver, muscle, bone marrow
cells, fibroblasts
Factor VIII
Factor IX
Familial
hypercholesterol
aemia
liver Low-density lipoprotein
receptor
Severe combined
immunodeficiency
bone marrow cells, T cells Adenosine deaminase (ADA)
Haemoglobinopathies
red blood precursor cells a-globin, b-globin
Cystic fibrosis
lung airway cells Cystic fibrosis gene (CFTR)
Gaucher’s
bone marrow cells,
macrophages
glucocerebrosidase
Cancer tumor cells p53, Rb, interleukins, growth-
inhibitory genes, apoptosis genes
Z vnosom gena za protismiselno RNA lahko to RNA v celici izrazimo in nato
ta komplementarno blokira nezaželeno mRNA.
Nanjovejiš pristop raziskuje možnost uporabe “majhne interferenčne RNA”, ki jo naredimo
tako, da je komplementarna mRNA (oz. delu gena z mutacijo), ki jo želimo onesposobiti.
STEM CELL Therapy
Različne vrste matičnih celic imajo različno sposobnost diferenciacije v druge celične tipe
in od tega je odvisna tudi njihova (specifična) uporabnost za zdravljenje poškodb tkiv in
organov.
In vitro
fertilization
Pridobivanje pluripotentnih embrionalnih matičnih celic iz postopka oploditve z biomedicinsko
pomočjo.
Pridobivanje pluripotentnih embrionalnih matičnih celic s postopkom kloniranja s prenosom jedra.
Oploditev z biomedicinsko pomočjo s predimplantacijsko diagnostiko (2) (leva stran slike: 1, 2, 10). Zarodno
gensko zdravljenje (desna polovica slike; postopek še ni dovoljen): predimplantacijska diagnostika (2), celično
kloniranje (3), genska korekcija (4), selekcija in kontrola (5-8), kloniranje s prenosom jedra (9), implantacija (10).