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

http://www.answers.com/topic/gene-therapy-jpg

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).