Supported from 2005 to 2021 by the National Cancer Institute, this partnership between the IIN and the Robert H. Lurie Comprehensive Cancer Center officially united scientists, engineers, and clinicians at Northwestern for the first time. Research advanced the understanding of metastasis and led to the development of novel nanoscale materials for cancer therapeutics.
Under the leadership of Professor Chad A. Mirkin and Dr. Leonidas Platanias, the CCNE featured three projects (one discovery-based and two translational), and one core facility to learn about the genetic basis of this highly heterogeneous disease class and how it can be analyzed and treated using genetic approaches.
Due to their novel size-, shape-, and composition-dependent chemical, biological, and physical properties nucleic-acid based nanomaterials can be used to gain access to privileged intracellular environments, discover new aspects of cancer biology and genetics, and exploit nanostructure-biomolecular interactions to create effective treatment options.
NU-CCNE explored these vast possibilities by applying a novel class of nanostructure genetic constructs – the spherical nucleic acid (SNA) and variants of it – for the study and treatment of brain (glioblastoma multiforme (GBM) and prostate cancer (pCa).
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