WHAT IS GENE THERAPY?

Substitution of defective genes in a cell with genetically altered genes. Or

Introduction of genetic material to compensate for abnormal genes or to make a beneficial protein.

·         TYPES OF GENE THERAPY                                                                                              GERM or REPRODUCTIVE

Insertion of allele into gametes or early embryo. Allele is passed on to off springs or germ line.

§                                                                                     SOMATIC                                                                                                      Cells are targeted for gene replacement. Correct allele is placed in body cells .Process is corrective for only patient.

§                                                                                             VECTORS:                                                                                    Systems that enable genes to be delivered to cell. They Transfer, Protection and Transcription of gene. Vector should be:

1.       Less expensive

2.       Easy to produce

3.       Purified in large amounts                                                                                                                                                                                     

v  VIRUSES

Genetically engineered so as to not replicate and thrive in huge numbers to kill cells. VIRUSES

Examples are Retroviruses, Lentiviruses, Adeno-associated viruses.

To deliver a gene in a location, use a virus that attacks that location.

v  LIPOSOMES                                                                                                                                                 Small spheres of phospholipid. Fuse up with target cell membrane and release gene into target cell .Trial for introducing normal allele of CFTR gene into liposomes, then sprayed into noses of patients.                                                                                                                                                                        

v  NAKED DNA                                                                                                                                                      Trails for skin, muscular and heart disorders .This method removes the problems associated with using other vectors

REASONS FOR CHOOSING VECTORS

1.       Efficiency; Monogenetic disorders [caused by a single gene], viral vectors are used.

2.       Span of immune response; In short term expressions, liposomes are used.

3.       Depending on size of target cell; if target cells are big, herpes viruses are used.

4.       Depending whether target cells are dividing or non-dividing.                                        CHALLENGES IN CHOOSING VECTORS                                                                                                                                                                                        
      RETROVIRUSES                                                                                                                                                      Patients may develop leukaemia after gene therapy for X-linked Severe Combined Immunodeficiency (SCID).  They randomly insert genes into host’s genome, hence  they insert their genes within another gene or into regulatory sequence of a gene which may activate neighbouring genes ,leading to cancer.                                                                                                                                                                                      LENTIVIRUSES

Inserts gene randomly into a host genome but can be modified to inactivate replication.                         HIV has been disabled to act as such a vector.

·          ADENO-ASSOCIATED VIRUSES

Virus does not insert its gene into the host genome .This is a problem when host cells are short-lived.

·         LIPOSOMES

Received by a few cells lining the nose .Effects only last for a week.                                           

·          NAKED DNA

Injection of naked DNA can be done by gene gun process. This involves a gold particle covered with corrective DNA and inserted into the cell. This process damages cell membrane.

               SOCIAL AND ECONOMIC CONSIDERATIONS OF GENE THERAPY

1.       Due to technology, treatment is very expensive.

2.       Manipulating the genetic make-up of man is unacceptable because altering the gene is similar to interfering with nature.

3.       Unappreciated due to other simpler method; Drugs.eg:PTC124 allows CFTR to be made to relief symptoms of Cystic fibrosis.