Gene Therapy

Severe combined immunodeficiency [Ref KDT 6^m/e p. 843, 8441

Gene therapy

• Gene therapy refers to introduction of functional genetic material usually D.N.A. into target cells to replace or supplement defective genetic material.
• In contrast to all other therapies or drugs, gene therapy imparts, new functions to a cell.
• Gene defects result in_.fallure to synthesize a functional protein or in the synthesis of a dysfunctional protein.
• Equipping the cell with a normal copy of the defective gene would overcome the deficieny at the site where it is needed on a long term.

Approaches in gene therapy 😕

• Gene therapy tries to either modify or transfer the genes.

Gene modification

• This involves correction of the defective portion of a genomic sequence or removal of the whole defective gene and its replacement by a normal copy.

Gene transfer

• This involves introduction of genes without removing or altering the existing ones.

Gene transfer is carried out in the following ways?

i)      Injection of naked D.N.A.

ii)     Transfer of generic material using virus as a carrier with D.N.A. incorporated into its genome.

iii)    Transfer of D.N.A. encapsulated within a liposome

Applications of Gene therapy (where genetherapy is being considered) 😕

• Cystic fibrosis (insertion of CFTR gene into respiratory epithelial cells)
• Severe combined immunodeficiency disease (introducing genes for adenosine deaminase)
• Growth hormone deficiency
• Familial hypercholesterelimia
• Lysch Nyhan syndrome
• Parkinsonism
• Alzhiemer’s disease, Huntington’s chorea. Familial amyotrophic lateral sclerosis, Gaucher’s disease
• Stroke, head injury, multiple sclerosis
• Duchenne muscular dystrophy
• Prevention of restenosis of grafted coronary vessel
• Anemia
• Sickle cell anemia
• Haemophilia
• HIV infection
• Cancers

Current status of Gene therapy (www.Fda.gov/Biologic.s bloodvaccines/cellular gene therapy)

• The food and drug administration has not yet approved any human gene therapy product for sale.

– Current gene therapy is experimental and has not proven very successful in clinical trials.

– Clear cut success in gene therapy has been achieved in Severe combined immunodeficiency (adenosine deaminase deficiency).

– But there were reports that children treated with gene therapy in severe combined immunodeficiency developed leukemia.

– Based on current data, the efficacy of gene transfer_{, .}for severe combined immunodeficiency is convincing there have been no complications in the six children treated on this protocol, but longer term follow up

will be required to determine whether this approach is sufficiency safe to he used in place of pegylated form of the enzyme adenosine deaminase.

A i.e. Replacement of abnormal gene by normal gene.

A i.e. Electroporation, B i.e. Intranuclear infection, C i.e. Site directed mutagenesis

A i.e. SCID

– The goal of gene therapy is replacement of abnormal mutant gene by normal geneQ.

– Technique to transfer genes (foreign material) into cells include – transfection, microinjection, electroporation, site directed recombination, transduction using adenovirus or retrovirus and plastnid liposome complexQ etc.

SCID (Severe combined imuunodeficiency disease) or bubble baby syndrome is the first disease treated successfully by gene therapy.

Ans. is ‘a’ i.e., Electroporation; ‘c’ i.e., Selectively targeted recombination

Gene therapy

o Gene transfer is a novel area of therapeutics in which the normal gene (DNA sequence) is delivered to target somatic cells.

o Because delivery of naked DNA or RNA to a cell is inefficient process, most gene transfer is carried out using a vector (gene delivary vehile).

Methods of introducing genes into cells for gene therapy

o Intranuclear injection                     o Electropolation                 o Plasmid liposome complexes o Adenovirus

o Transfection                                   o Retroviruses                      o Site directed recombination