2. Genetic Testing and Ethics Flashcards
Define genetic therapy and gene therapy
Genetic therapy - includes any treatment or medical intervention for genetic disorders or a treatment that uses a genetically based technology regardless of the disease etiology.
(Medication or recombinant vaccine)
Gene therapy - treatments in which there is actual manipulation of the patient’s DNA to produce a therapeutic response.
(Introduce gene into genome, silence abnormally functioning gene)
components of managing a genetic disease
Genetic Counseling
Interdisciplinary specialty teams
10% can treat
50% manage but not treat
35% no effective tx
approaches in treating genetic disorders
Genetic Deficiency
Positive Harmful effects
Alter Susceptibility
Describe the approach used to treat a genetic deficiency and give examples
Genetic Deficiency:
Augmentation therapy: something is provided to the patient that supplements a severely depleted, or missing factor.
Eg., cochlear implants or hearing aids to treat hereditary deafness, replacing a missing enzyme - inborn errors of metabolism.
Positive Harmful Effects:
The harmful effect might be treatable - developmental malformations: corrective surgery, eg., congenital heart defects, cleft lip and palate, etc
Dysmorphic features we correct through surgery
Describe the approach used to treat a positive harmful effect and give examples
gene inhibition therapy
cell containing faulty gene - add blocking gene - new gene product blocks faulty gene - cell functioning normally
Describe the approach used to alter disease susceptibility and give examples
Key susceptibility factors can be manipulated to reduce the chances that a disease will recur, or to reduce the effects of a progressive disease.
EX:
mutations in LDL receptor apolipoproetin B or PCSK9 - liver with only 50% functional LDL receptors - elevated LDL cholesterol - atherosclerosis -
introduce statins!!!
small molecule drugs
MOA: works by binding to a specific target protein that has a key role in the pathogenesis—often a receptor, ion channel, or enzyme.
EX: Gabapentin – anti-epileptic & neuropathic pain
Minoxidil
Sildifineil
Drug ‘repurposing’ is valuable because the drug has already been through lengthy and expensive clinical trials to assess its safety profile.
genetic engineering
MOA : Therapeutic ‘recombinant’ proteins and genetically engineered monoclonal antibodies. Eg., treatment and diagnosis of cancer, rheumatoid arthritis, etc
EX: Recombinant vaccines - made with the aim of combating certain types of pathogen more effectively, eg., Hep B vaccine.
-mab (monoclonal antibodies)
principle of gene therapy
Gene therapy involves the direct genetic modification of cells to achieve a therapeutic goal. The genetic modification can involve the insertion of DNA, RNA, or oligonucleotides.
Germ-line gene therapy
most controversial - not used
produce a permanent modification that can be transmitted to descendants; this could be achieved by modifying the DNA of a gamete, zygote, or early embryo.
Somatic cell gene therapy
seeks to modify specific cells or tissues of the patient in a way that is confined to that patient
Identify the two different strategies in somatic gene therapy and give examples for each
Most commonly use viruses - Adenoviral vectors
Disease cells are simply modified (direct cell killing through suicide gene)
They are selectively killed
(gene silencing - stop mutant protein form being made) - immune activator - indirect killing
Recognize the ethical concerns and the tremendous potential of cloning
Ethical concerns have overshadowed the tremendous potential that cloning has for the treatment of human disease.
Therapies for spinal cord injuries or neurodegenerative conditions, normal aging - nerves cannot regenerate, with cloning you can do this
Alleviate graft issues and the need for cadaver-source donors - prevents need for organ donation and prevents rejection of organs
Discuss the problems in gene therapy, including tissue accessibility, turnover, efficiency, safety, patient recruitment, duration and cost
Access to the desired target cells – Blood vs Brain
Dividing vs Non-dividing cells
Efficiency and safety
Integrating (Merge w your genome, off target effetcts) vs Non-integrating viral vectors (stay outside genome, effect is transient)
Viral vs Non-viral delivery methods
Problems in finding / recruiting patients
Duration of clinical trials
Cost
For the great majority of genetic conditions, even for single-gene disorders, existing treatments are lacking or unsatisfactory.
Discuss how CRISPR/Cas9 is used for gene editing and recognize its advantages and disadvantages
CRISPR/Cas9 is a gene editing tool that can manipulate gene expression in plants, humans and animals.
GuideRNA with a specific sequence - Cas9 enzyme - does actual cutting
The enzyme will search for anything with that specific code and cut it up, yielding a window to implant a desired DNA sequence.
Once the sequence is planted, the strands are sealed and the target sequence will be expressed.
Only technique that is highly efficient and precise, extremely customizable and can target multiple genes at once.
