ch 12: gene therapy

• Biotechnology – technology that utilizes biological systems, living organisms, or parts, to develop/create different products

  • Biotechnology has tremendous applications in different fields like:
  • Therapeutics
  • Diagnostics
  • Processed food
  • Waste management
  • Energy production
  • Genetically modified crops
  • More
• BIOTECH applications:

  1. Agriculture
  2. Health care
  3. Environment
  4. Industry
• Agriculture

  • GM planting mats. and hybrids
  • Micropropagation
  • Bio-fertilizers and bio-pesticides
  • Animal improvement
• Health care

  • rDNA products, vaccines, and diagnostics
  • Monoclonal antibodies
  • Stem cells
  • Tissue specific delivery methods
• Environment

  • Soil and water remediation
  • Bio-safety and GMOs
• Industry

  • Enzymes
  • Fermentation based products and food
  • Biotech instruments and equipment
  • Bio-energy and bio-fuel
  • Bioinformatics, biomining
• GENE THERAPY – technology that works on manipulating the genome to correct defective genes to treat heritable disease
• Gene therapy is a therapeutic strategy that use genetic engineering techniques to cure diseases/disorders caused by a genetic problem

  • Various disorders like Severe Combined Immunodeficiency (SCID), Hemophilia, Diabetes, Cystic Fibrosis, Heart disease, AIDS, and even problems of aging
• Gene therapy

  • Allows correction of disease causing mutations to prevent the onset of disease and involves the process known as Gene Editing
• Gene editing 

  • results in modified genes
  • More precise than genetic engineering
• Genetic engineering – targets a specific sequence
• Gene editing – the faulty gene are corrected/edited by inserting “good genes”
• Genes – blueprint of life that carry information responsible for an individual’s traits

  • Genes are the genetic materials in our body cells, often called Deoxyribonucleic acid (RNA)
  • DNA/genes  contain the instruction that directs the cells in our body to make proteins
  • Proteins  do varied tasks in our cells
  • E.g. produces pigments, makes muscles strong, and kills bacteria that invades our cells
  • Keratin (protein) for example, is produced by specific genes in the cells of our body to form the skin and fingernails
• GENOME – complete set of DNA/genes in a cell/organism

  • It contains all the information needed by the cells in out body to build, grow, and develop
  • A Human genome consists of 46 chromosomes
  • In homologous pairs
  • Each pair contains paternal and maternal chromosomes
• Each human cells have;

  • 23 pairs of chromosomes
  • 22 pairs are autosomes (non-sex chromosomes)
  • 1 pair is a sex chromosome (X and Y)

  These chromosomal pairs dictate the organisms characteristics
• A chromosome consists of 2 CHROMATIDS known as SISTER CHROMATIDS

  • Sister chromatids contain sequences of DNA
  • The nucleus of the cell houses the DNA
  • DNA is a double helix structure consisting of 2 strands
  • Each strand is composed of genes with chemical bases such as Adenine (A), Thymine (T), Guanine (G), and Cytosine (C)
  • Changes in the sequence will result in genetic disorders
• GENETIC DISORDERS

  • Diseases caused by mutation/change in the DNA sequence of an individual
  • These mutations can either be due to an error in DNA replication/environmental factors like diet and lifestyle that can trigger these diseases
  •  Can occur in one gene, or there is an extra or missing chromosome
  • A change in a particular portion of our DNA affects the proteins that the genes code for
  • Correcting DNA sequences to treat genetic disorders is where gene therapy application becomes useful
• SINGLE-GENE DISORDERS – mutations in specific genes

  1. Autosomal single-gene

  • Happens when the altered genes occur in the 22 pairs of non-sex chromosomes
  • Eg sickle cell anemia, cystic fibrosis, and Tay-sachs disease

  1. X-linked disorder

  • Diseases which the altered genes occur in the sex chromosomes, specifically the X chromosome
  • Eg. Duchenne Muscular Dystrophy, Hemophilia, and color blindness
• Klinefelter syndrome

  • Extra X chromosome (since birth)
  • XXY instead of XY (men)
  • Aka XXY syndrome
• 1. Turner Syndrome (Monosomy X)

  • Only 1 X chromosome (females)
• Down Syndrome (Trisomy 21)

  • Extra copy of chromosome 21
  • Cause body and brain to develop differently than a child without the syndrome
• Patau’s Syndrome (Trisomy 13)

  • Additional copy of chromosome 13
• Edward’s Syndrome (Trisomy 18)

  • Caused by the presence if all or part of an extra 18th chromosome
• MULTIFACTORIAL INHERITANCE (Complex or Polygenic Inheritance)

  • Changes in multiple genes combined with environmental and lifestyle factors such as diet/smoke caused multifactorial inheritance
  • Eg. high blood pressure, Alzheimer's. Arthritis, diabetes, cancer, obesity, heart disease
• Gene therapy – method of treating/preventing disease by replacing or turning off/on of a patient’s cells (Bautista et al, 2018)
• Gene therapy helps treat genetic disorders and focuses in correcting defective genes by;

  1. Randomly inserting a normal gene into the genome (most common technique)
  2. Replacing the abnormal gene with the normal gene
  3. Repairing the abnormal gene
  4. Altering regulation of a particular gene
• Gene therapy method of treating conditions…

  • Involves using vectors (Viral methods)
  • Involves using without vectors (non-viral methods)

  … to move DNA/gees to one cell
• Vectors (viral methods) are vehicles/agents used to introduce/insert genes into the cell

  • Some gene therapy vectors include retrovirus, adenovirus, adeno-associated virus, cis and trans-acting elements, and herpes simplex virus
• Without Vectors (non-viral methods)

  • Simples way: injection of the naked DNA
  • Has more advantage than vectors (viral methods) because if can produce DNA on a large scale
• Transgenic or Genetically modified – cells, tissues, and organisms where gene therapy is employed
• TYPES OF GENETIC THERAPY

  1. Somatic gene therapy
  2. Reproductive Gene Therapy or Germ-line Cell Therapy
• Somatic Gene Therapy

  • Genes are introduced to cells in the target organ (non-sex cells) to produce enzymes needed by the body without altering the organism’s genetic makeup
  • Changes are not transferred to the offspring
  • Not related to reproductive gene therapy
• Reproductive Gene Therapy or Germ-line Cell Therapy

  • Introducing corrective genes to sex cells (sperm and egg cells) or to 4-day old zygotes
  • Removes abnormalities that the offspring may inherit
• In gene therapy, medical experts must correctly identify the genes responsible for the disease. The modified gene must reach the cell/target organ accurately,controlled, and effectively.

  • Note that cells can reject modified genes because of the body’s natural defense system that causes gene therapy failures
• TWO APPROACHES OF GENE THERAPY

  1. Ex vivo  – transfer of genes in cultured cells, and reinjected to the body of the patient
  2. In vivo – introduction of therapeutic gene into the vector injected directly to the body

  • Can be carried out using viral or non-viral vectors
• Vector – carrier particles/molecules used to deliver genes

  1. Nonviral vectors – depend on physical/chemical methods of delivering genetic material into a cell

  • Physical technique: needle
  • Chemical technique: created in a lab

  1. Viral Vectors – use the blueprint of a virus–not the actual virus itself
• Why are viruses used to deliver gene therapy?

  • Viruses provide an ideal model for delivering gene therapy to a host cell which is the target location where a researcher will want gene therapy to treat a genetic mutation
  • Viruses have natural designs, which are very effective at entering a cell
  • Similar to how a delivery truck can easily navigate the neighborhood and deliver packages
• Scientists have created blueprints/mapped the complete genome (series of genes) of many viruses

  • Able to isolate parts of virus genome that are effective at entering cells
  • Removes the part of virus that causes disease
  • Only the safe part of virus blueprint are used
• Benefits of gene therapy

  1. Offers cure for cancer, parkinson’s disease, AIDS, asthma. Diabetes, heart diseases, hereditary diseases
  2. Replace defective cells
  3. promising potential in many fields
• disadvantage of gene therapy

  1. Modifying organisms = modifying capabilities
  2. Viral vectors could recover their ability to cause disease
  3. Can damage gene pool, result in multigene disorder
  4. High cost
  5. Ethical issues