Unlocking anti-tumor potential: CRISPR-enhanced LW-11 peptide investigation in glioblastoma cells (U-138 MG)

• Grant number: 24/22043-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Catarina Raposo Dias Carneiro
• Grantee: Natália Barreto dos Santos
• Supervisor: Debora Rodrigues Sobreira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of California, Los Angeles (UCLA), United States
• Associated to the scholarship: 23/14743-7 - Analysis of the mechanisms of action of a peptide synthesized from a spider venom prototype in human glioma cell lines, BP.PD

Abstract

Malignant gliomas are the most common primary brain tumors in adults. Characterized by their high diffusion through the brain parenchyma, these tumors are associated with a poor prognosis. Glioblastoma (GB), the most aggressive type, has a survival rate of less than two years post-diagnosis. Current treatments, including surgery, radiotherapy, and chemotherapy, are often insufficient due to the tumor's infiltrative nature and treatment resistance. Venom peptides have emerged as potential anticancer agents due to their effects on tumor cell migration, proliferation, and angiogenesis. Recently, our research group has demonstrated that Phoneutria nigriventer spider venom (PnV) exhibits significant antitumor effects on GB cell lines, reducing cell viability, proliferation, and migration. We also identified LW-11, from PnV, as the most effective molecule in inhibiting the migration of GB and other glioma cell types. Chromatography analysis identified that LW-11 is a peptide (1174.65 Da). To develop a new drug, it is essential to evaluate the molecular mechanism of this peptide. This project aims to explore the molecular mechanisms underlying LW-11's effects on glioma cells using RNA-seq and CRISPR/Cas9 technologies. These techniques will be learned at University of California, Los Angeles (UCLA) and subsequently implemented at LATERA (Laboratory of Advanced Therapies; Unicamp, Brazil) to support further glioma research and the development of potential new therapies.