The Twist of Silence: Our DNA isn’t just a linear code, it folds and loops to control gene silencing activity. A new USC study unravels how these loops act as silencers, keeping key developmental genes in check.
Unmasking the Guardians:
PRC1 & PRC2: These molecular guardians lock developmental genes away, preventing their inappropriate activation.
The Looping Act: Repressed genes form loops, bringing them closer for PRC1 and PRC2 to bind.
Breaking the Silence: Without loops, these genes escape their silence, potentially leading to developmental issues or even cancer.
Key Findings:
- A protein called PDS5A maintains these loops, crucial for gene silencing.
- Disrupting PDS5A unlocks silenced genes, revealing their dependence on loop formation.
- This discovery sheds light on how cohesin mutations linked to diseases might affect gene silencing.
Impact:
- Understanding gene silencing opens doors for potential therapies targeting diseases linked to disrupted gene control.
- This research lays the groundwork for future studies on cohesinopathies and their impact on gene regulation.
Infographic:
The Looping Dance of Gene Silencing:
- Developmental genes, guarded by PRC1 & PRC2, form loops in the DNA.
- PDS5A protein strengthens these loops, keeping genes silenced.
- Disrupting PDS5A breaks the loops, unleashing gene activity.
Breaking Discovery: Silencing Genes Overcomes Chemoresistance in Head and Neck Cancer
In a groundbreaking study led by Queen Mary University of London, researchers have identified two genes responsible for chemoresistance in head and neck cancer. The findings, published in Molecular Cancer, reveal that silencing these genes can make cancer cells responsive to chemotherapy.
Key Findings:
Identified Genes: NEK2 and INHBA were identified as two genes causing chemoresistance in head and neck squamous cell carcinoma (HNSCC).
Broad Applicability: These genes are found to be active in most human cancer types, suggesting potential applicability to other cancers exhibiting elevated levels of these genes.
Chemical Library Exploration: Researchers explored a chemical library for drug discovery and found two substances – Sirodesmin A (a fungal toxin) and Carfilzomib (from a bacterium) – that target the identified genes, making resistant cancer cells significantly more sensitive to cisplatin, a common chemotherapy drug.
Drug Repurposing: The study indicates the potential for repurposing existing drugs, like Sirodesmin A and Carfilzomib, to target chemoresistance genes, offering a cost-effective approach compared to developing new drugs.
Clinical Implications:
Personalized Treatment: The research suggests a promising step towards personalized cancer treatment based on individual genes and tumor types, leading to better survival rates and treatment outcomes.
Addressing Chemoresistance: Overcoming chemoresistance in head and neck cancer could potentially improve treatment efficacy and patient outcomes.
Cost-Efficiency: Repurposing existing drugs may offer a cost-effective solution for developing targeted therapies against chemoresistance.
Significance:
Prevalence of HNSCC: Head and neck squamous cell carcinoma accounts for 90% of all head and neck cancers, with tobacco and alcohol use being major risk factors.
Survival Rates: The overall 5-year survival rate for patients with advanced HNSCC is less than 25%, highlighting the need for breakthroughs in treatment strategies.
Current Challenges: Standardized treatments for HNSCC patients, irrespective of genetic makeup, contribute to treatment failures and poor survival rates.
The study’s senior author, Dr. Muy-Teck Teh, emphasizes the potential of targeting specific genes to combat chemoresistance, offering hope for improved cancer treatment outcomes.
Drug Delivery Breakthrough: Berkeley Lab & Genentech Team Up on LNPs
Problem: Drugs often struggle to reach their target cells in the body, limiting their effectiveness.
Solution: Lipid nanoparticles (LNPs) – tiny fatty pouches that carry drugs to cells.
The Research:
- Berkeley Lab & Genentech collaborate to design better LNPs.
- High-throughput workflow rapidly creates & analyzes hundreds of LNP formulations.
- Small-angle X-ray scattering (SAXS) reveals LNP structure & stability.
- LNP structure linked to drug activity in cells (ASO silencing faulty gene).
Benefits:
- Improved drug delivery for vaccines, gene therapy, and more.
- Faster development of new & effective treatments.
- Broader application of LNP technology beyond mRNA vaccines.
Key Takeaways:
- LNPs are promising drug delivery vehicles with vast potential.
- High-throughput research accelerates LNP development and optimization.
- Understanding LNP structure & activity paves the way for better drugs.
