NU-CCNE Project 1

Design Rules for SNAs that Target Cancer

Primary Objectives

  • Identify design rules for optimal efficacy of SNAs for glioblastoma and immunotherapy against prostate cancer
  • SNAs for glioblastoma and immunotherapy against prostate cancer

Transformative Potential

  • Bring the best practices from traditional therapeutic development programs to nanomaterials
  • Identify design rules that govern structure-activity relationships of nanomaterials
  • Understand the extent of heterogeneity and its role in SNA uptake and knockdown
NU-CCNE Project 2

SNAs for Metabolic Reprogramming of Glioblastoma

Primary Objectives

  • Use siRNA-conjugates Spherical Nucleic Acids (SNAs) that targets Isocitrate Dehydrogenase1 (IDH1) to reprogram glioblastoma metabolism
  • Exploit BBB/BTB penetration of systemically delivered SNAs to downregulate IDH1 expression in glioma

Transformative Potential

  • Glioblastoma is the most prevalent and aggressive manifestation of primary brain cancers
  • Rational design of SNAs as gene regulatory agents: modular, chemically well-defined nanostructures
  • Targeting of glioma-associated IDH1 upregulation as a key genetic element of metabolic adaption, and putative driver of unabated tumor growth and therapy resistance
  • Combination Therapies: using siIDH1-SNAs plus RTKi to promote apoptosis of RTKi, which primarily have cytostatic activity only
NU-CCNE Project 3

SNAs as Immunotherapeutic Agents for Prostate Cancer

Primary Objectives

  • Spherical Nucleic Acids (SNAs) as a Cancer Vaccine: A treatment for prostate cancer that stimulates and targets the immune system to attack prostate tumors
  • Exploit the interaction of SNAs with cells of the immune system to induce tumor-specific T-cell activity

Transformative Potential

  • Prevalence of Prostate Cancer (most common, non-skin cancer in the U.S., 2nd leading cause of cancer-related death in U.S. men)
  • Design of SNAs as Immunotherapeutic Agents: chemically well-defined nanostructures (core, oligonucleotide, peptide antigens)
  • Potential for Combination Therapy: Strategy of SNA + checkpoint inhibitor provides addresses both challenges of immune stimulation and suppression
NU-CCNE Project 4

Oligonucleotide Synthesis and Nanoconstructs Core

Primary Objectives

  • To optimize and scale the spherical nucleic acid (SNA) platform for all projects in the CCNE

Transformative Potential

  • Optimize constructions for intended applications (e.g., nanoparticle core composition, oligonucleotide sequence and loading, incorporation of ancillary ligands)
  • Provide a standardized, scalable platform to screen in vitro efficacy of SNAs
Researchers
Leader

Teri Odom

Co-Investigator

SonBinh Nguyen

Collaborators

C. David James

Chad A. Mirkin

Samuel Stupp