As seen in the video, nucleases can be engineered to create site specific, double strand breaks at desired locations in the genome. Antisense Oligonucleotides can be thought of as our "molecular scissors" that guide the gene editing process.
A First-In-Human, Phase 1B, Dose Escalation Study of QR-010, A Novel Antisense Oligonucleotide Administered in Subjects with Cystic Fibrosis Homozygous for the F508Del CFTR Mutation. Elborn, S.
|Pro-QR's treatment is called "QR-010"|
|An "antisense oligonucleotide" is a synthesized strand of nucleic acid that is complementary to the gene's messenger RNA.|
Pro-QR's treatment was administered to the lungs via nebulizer.
|Goals are to establish safety and tolerability, as well as assess maximum tolerated dose (MTD).|
|CFQ-R= Cystic Fibrosis Questionairre-Revised, RSS= Respiratory Symptom Score|
|Quality of life improvements were patient reported using the Cystic Fibrosis Questionnaire-Revised (CFQ-R), and the Respiratory Symptom Score (RSS)|
|Wow! Just Wow!!!!!!|
Antisense Oligonucleotide-Mediated Upregulation of CFTR via Steric Block of Post-Transcriptional Control Elements: A Novel Approach for Cystic Fibrosis Therapeutics. Sasaki, S.
|Antisense oligonucleotides function as our "molecular scissors."|
|Antisense oligonucleotides are programmed to target a specific site.|
|Could this type of treatment be successful for gene transfer in CF lungs?|
|ASOs = antisense oligonucleotides (our molecular scissors).|
In Utero Nanoparticle Delivery for Site-Specific Genome Editing. Ricciardi, A.
|The CFF registry has confirmed that early diagnosis and intervention leads to better health outcomes.|
|We have the ability to detect CF in developing fetuses.|
|The fetus is deeply affected by cystic fibrosis--even prenatally.|
|Could in utero gene editing PREVENT cystic fibrosis altogether?!?!|
|Stay with me here! Remember, PNA is our pair of "molecular scissors," programmed to make the cut at a specific target.|
|One of the most important things about this research is the FORMULATION of their genetic product. They do this special "nanoparticle" thing--where they cram all the genetic info onto these itty bitty spheres.|
|The PNA/DNA nanoparticles work to correct the F508del mutation in living mice.|
|So they decided to test their treatment on a developing CF mouse embryo...|
|Holy crap, is that a mouse uterus?!|
|Researchers have to use specially made glass pipettes to inject their nanoparticles into this particular vein in the uterus.|
|So cool. This is the actual injection of the nanoparticles into the uterine vein.|
|Researchers were able to show uptake and expression of desired genetic information in fetal organs!!!|
|In conclusion...holy shit. This talk left my jaw hanging open!|
As previously noted, perfecting the "vector" to enhance gene delivery was a hot topic because it has proven to be so challenging over the years.
Manipulating Vector Interactome to Enhance Gene Delivery. Siefert, M.
|Researchers have encountered multiple obstacles to success gene transfer.|
|Another example of nanoparticle delivery. Could this be the way forward?|
|Safe, but not perfect.|
|How do we improve efficacy?|
|Penetrating mucus is a formidable barrier in CF.|
|Manipulation of other cellular interactions can enhance gene transfer.|
|It is worth taking a closer look at how to achieve maximal benefit from manipulation of these cellular interactions.|
|Researchers were able to show improved efficacy of their gene product by manipulation of cellular interactome.|
What an amazing world we live in. Cure Cystic Fibrosis.