Highlights:
Genetic blood disorders like thalassemia, sickle cell anemia
and primary immunodeficiency syndromes can be cured by using CRISPR gene
editing techniques. However, the challenge remains in the side effects of gene
editing which is cancer. Stem cells have a way of responding to gene editing by
shutting down and this process actually increases the risk of cancers.
Scientists at the San Raffaele Telethon Institute for Gene
Therapy in Milan have found a way to make genome editing safer for blood
disorders minus the side effects. They used more precise gene editing
techniques like specific nucleases and vectors to induce fewer breaks in the
DNA thus controlling the stem cells’ natural damage response pathways. - Genetic blood disorders like thalassemia, sickle cell anemia and primary immunodeficiency syndromes can be cured by using CRISPR gene editing techniques
- Stem cells have a way of responding to gene editing by shutting down and this process actually increases the risk of cancers
- Scientists have found a way to make genome editing safer for blood disorders minus the side effects
- They used more precise gene editing techniques like specific nucleases and vectors to induce fewer breaks in the DNA thus controlling the stem cells’ natural damage response pathways
Tumor Suppressor Gene p53 may Also Contribute to The Spread of Cancer
Variant of the p53 gene, commonly known as tumor suppressor gene, increases tumor cell metabolism. A genetic variant of mutant p53 is associated with increased mitochondrial function and poorer prognosis for breast cancer patients.
Variant of the p53 gene, commonly known as tumor suppressor gene, increases tumor cell metabolism. A genetic variant of mutant p53 is associated with increased mitochondrial function and poorer prognosis for breast cancer patients.
‘CRISPR gene editing can be made safer for blood disorders without the unwanted side effects like cancers.’
Read More..Tweet it Now
Pietro Genovese, senior co-author said that despite the therapeutic potential of correcting blood disorders with
genome editing; the challenge has been to circumvent the serious side effects
like the
development of cancers. Read More..
Gene Editing can be made ‘Safer’ for Blood Disorders
p53 is a protein often termed the ‘guardian of the genome’ as it preserves the stability of DNA and prevents against unwanted mutations. When CRISPR is used to cut genes, it cuts the two strands of the DNA at a specific location. This action of cutting the DNA strands can actually send out a wrong signal to p53 communicating that there is something going wrong in the DNA.p53 then starts its action and prevents the cells from multiplying while the desired effect is actual proliferation cells as a therapeutic. The difficulty of p53 is that it cannot be silenced or shut down as this can lead to cancers. p53 is the body’s main defense mechanism against cancers.
The research team found a simple method to overcome this obstacle with p53. Gene editing techniques use genetic scissors like nucleases to induce DNA breaks and then uses a viral vector to insert the corrected sequence. If the genetic scissors are not specific, more than the required DNA breaks will be induced which gives out the wrong signal to p53.
Use of Specific Nucleases and Vectors
The team used specific nucleases and vectors to induce only the intended DNA breaks in hematopoietic stem/progenitor cells (HSPCs).
Mutant P53 Gene Fuels Cancer-promoting Effects of Inflammation
Instead of suppressing tumor growth, mutant forms of p53 gene fuel pro-inflammatory responses that increase cancer growth, says study.
Instead of suppressing tumor growth, mutant forms of p53 gene fuel pro-inflammatory responses that increase cancer growth, says study.
Rafaella di Mico, third author and head of a lab at the institute said that HSPCs tolerate only a few DNA breaks with transient p53 activation. Inactivating p53 response temporarily during gene editing can improve the yield of cells with greater proliferation and desired effects without disturbing the genome’s stability or increasing the risk of unwanted mutations.
Advertisement
Unmutated Form of P53 Protein is the Key to Cancer Prevention
New enzyme pathway that plays a role in anticancer protein p53 has been discovered by scientists. Oncogene p53 has two faces, i.e its unmutated form prevents cancer while mutated form leads to aggressive cancers.
New enzyme pathway that plays a role in anticancer protein p53 has been discovered by scientists. Oncogene p53 has two faces, i.e its unmutated form prevents cancer while mutated form leads to aggressive cancers.
References:
- Precise Gene Editing Preserves Hematopoietic Stem Cell Function following Transient p53-Mediated DNA Damage Response- (https://doi.org/10.1016/j.stem.2019.02.019)
Advertisement
Stanford-led Study Uncovers Secrets of P53 Tumor Suppressor
Mutation in the p53 tumor suppressor has been recently uncovered by a Stanford-led study. The study reveals how mutation supercharges the gene combat tumors.
Mutation in the p53 tumor suppressor has been recently uncovered by a Stanford-led study. The study reveals how mutation supercharges the gene combat tumors.
