L9: New trends in biotech Flashcards
what is the biotech evolution?
discovery of the following in sequence:
Biotech 0.0: small molecules and recombinant protein
Biotech 1.0: mAbs and Fc fusion
Biotech 2.0: gene transfer and gene therapy
Biotech 3.0: neoantigens and microbiome
Biotech 4.0: engineered gene, extracellular vesicles, digital therapeutics, mitochondria regulation
what is Kendall square?
the heart of biotech, located in cambridge, with many internationally recognised innovation district for research
state the 2 main elements that makes Kendall square a good ecosystem for biotech
due to presence of Lab central and Flagship Ventures
How does the presence of Lab central and Flagship Ventures make Kendall square a good ecosystem?
Lab central: an incubator for start up companies. people from MIT are innovative and retn space to start proj once approved. can propose projects to investors eg. flagship ventures and prove that pdt is able to be commercialised [a form of validation]
- big companies also move into lab central to look for talents and ideas
Flagship ventures: investor of lab central
what is the trending thing now?
developing gene therapy
how does gene therapy work? [4]
- gene replacement: replace non-working mutant gene w a healthy one, eg. over-express healthy gene is disease is loss of function
- gene silencing: inactivate mutant gene that is toxic for the cells
- gene addition: over-expression of a foreign gene to impact disease state
- gene editing: changes the genome by permanent manipulation
how are gene delivered?
- viral vectors: retroviruses, adenoviruses, adeno-associated viruses–> gene inserted into viral genome and then inserted into our genome when virus infect us
- non-viral vectors: liposomes, naked dna
problem w using viral vectors for gene therapies [2]
- retroviruses integrate viral genome randomly into human cells
- viral genome have promoters that contain other unwanted gene eg. oncogene Jesse Gelsinger
unique benefits of gene therapy [5]
- solve unmet needs: esp for treating rare diseases w few/no treatment options
- current approved therapies have high efficacy
- targets cause of disease
- reduce/eliminate need for other costly treatment eg bone marrow transplant w high risk of infection
- less expensive than doing screening to find specific small molecule to treat disease
why is developing gene therapy “better” than developing small molecule drug?
small molecule drug:
- takes a few years to screen for a compound w therapeutic effect
- more time needed to know how compound acts on body, mechanism [TAKES TOO LONG]
gene therapy: skips the screening steps, as we skip straight to gene associated with disease
most of the gene therapies in development are in which phase?
phase I/II
what is the Orphan Drug Act?
an incentive to develop drugs for rare diseases, using eg. tax credits, market exclusivity, application, reduced statistic requirement
current challenges of gene therapy [3]
- restoration of missing gene not alws sufficient to cure a disease
- there are limited popn of patients w rare disease for clinical trials
- challenging delivery of RNA and DNA
which has less side effects? using nanoparticles or viral vectors to deliver RNA/DNA?
nanoparticles, tho it can still elicit immune response
can nanoparticles be injected into systemic circulation?
no, can only inject into muscles
how to stabilise mrna vector? side effect of this meethod?
use polyethylene glycol. can cause anaphylactic shock
limitations of using viral vectors [4]
- immunogenicity
- limited payload capacity
- risk of insertional mutagenesis
- manufacturing challenge
limitations of using lipid nanoparticles [3]
- limited biodistribution
2.toxicity at high doses - low efficiency of endosomal escape
how does extracellular vesicles solve existing limitations in nucleic acid delivery? [5]
- are natural carriers of RNAs [siRNAs, mRNAs]
- offers great biocompatibility: robust uptake by many cell types, low toxicity and immunogenicity
- may avoid phagocytosis and multi-drug resistance
what cells are good sources of EVs?
red blood cells
which is better, using EVs from cell lines or RBCs and why?
RBCs is better.
Problem with EVs from cell lines:
-scale up and CMC, require MASSIVE cell culture to achieve single human dose
- safety: oncogenic components from cell lines may cause oncogenesis [her2,cmyc] and from genetic manipulation of cells
RBcs:
-no risk of oncogenesis and genetic material transfer
- sustainable since we have alot and is readily opbtained
- scalable: formation of RBC EVs can be accelerated in economical fashion
what does REGENT stand for?
red cell EV gene therapy
why is REGENT an efficient delivery system? [3]
- large payload capacity: can put large amts of genes into EVs
- high copy number
- non-immunogenic
what are the manufacturing advantages of REGENT? [3]
- simple and fast loading method
- propriety surface modification method
-3. dont require expensive cell culture or genetic manipulation of cells
