Biologics (Cell Therapies. gene Therapy) Flashcards
(29 cards)
What are biological therapies?
- Peptides / recombinant therapies
- Gene therapy
- Cell therapy
- Monoclonal antibodies
What is gene therapy?
The transfer of genetic sequences that alter the DNA of a cell for therapeutic purposes
Delivery of genetic sequences that alter the instruction set of a cell for therapeutic purposes
What are the genetic sequences used in gene therapy?
- Synthetic copies of genes that encode a specific protein
- Short genetic sequences that knockdown the expression of a specific gene
Whats a variation of gene therapy?
Somatic cell gene therapy
What is somatic cell gene therapy?
Therapy is restricted to the patient and genetic material is not passed onto their offspring
What would the ideal gene therapy approach be?
- Be highly specific leading to reduced side effects
- Produce a long term therapeutic effect following a single application
What would ideal gene therapy involve?
Aim: To deliver the therapeutic gene to the organ/cell of interest
Problem: Mammalian cells are very efficient at getting rid of foreign DNA
Solution: Therapeutic genes are delivered using gene delivery vehicles
What are the gene delivery vehicles?
- Non-viral vectors : PLasmids, siRNA, lipsomes
- Viral vectors: Genetically modified viruses
How are viruses used as vectors?
- Exploit the natural life cycle of a virus
- Viruses bind to membrane bound receptors and have evolved efficient ways to gain access to the nuclear transcriptional machinery
- Remove the virus replication genetic material, left with shell, replace with therapeutic transgene
- most viral vectors nowadays are safe
How do viral vectors work?
-Penetrate a cell, use its nuclear machinery and produce therapeutic proteins(no viral genes replicated)
Whats the difference between ex-vivo and in-vivo gene therapy?
Ex-vivo = Genetic modification performed on cells in a dish before transplantation in the patient
In-vivo = Genetic modification performed directly in the patient
What does the success of gene therapy depend on?
Success of gene therapy depends on the efficiency of gene transfer
Whats the example for gene therapy?
Parkinsons disease
What does PD primarily affect?
Loss of dopamine cells in SNpc
Whats the stage one strategy for pd?
Dopamine replacement
How does dopamine replacement work?
Aim: Increase dopamine synthesis locally in the striatum
How: Transfer genes involved in dopamine synthesis to the neurons in the striatum
Problems: Does not prevent disease progression; amount of dopamine produced is hard to control
What is the second strategy for PD?
Neuroprotection
How does neuroprotection work for PD?
Aim: Boost production of growth factors involved that promote dopamine cell survival and axonal regeneration i.e glial cell derived neutrotrophic factor (GDNF) and Neurturin
How: Introduce GDNF or Neurturin genes into the brain
What is cell therapies?
Therapies involving the injection of living cells into a patient i.e bone marrow transplants
What are the types of cell therapies?
Autologous : Cells removed from patient, modified and returned
Allogenic : Cell donor is different person
Syngeneic : Cell donor is genetically identicle (twins)
What sorts of cells are used in cell therapy?
Cells can vary:
- Stem cells (cultivated into other cells)
- Blastocyte
- heDSC
- adult CNS
- Fetal CNS
- Bone marrow
- Fibroblast
How do cell therapies work?
- Replace damaged tissue
- Release therapeutic proteins
How does the replaced damaged tissues cell therapy work?
-Stem cells or progenitor cells are differentiated into a specific cell type in the lab. Cells are grafted into site of injury
How does the release therapeutic proteins cell therapy work?
- Transport cells that have the capacity to release soluble factors i.e cytokines, chemokines, growth factors
e. g insulin
