Cancer-Targeted Nanoparticles as a Novel Mode of Delivering RNA-based Therapeutics

Changes in alternative splicing have been shown to markedly contribute to the initiation and progression of cancer. This highlights the potential of modulating splicing as a plausible approach for cancer therapy. Modulation of splicing may be achieved using splice switching or decoy oligonucleotides. Still, these splicing modulating oligonucleotides in addition to other RNA-based therapeutics face the challenge of efficient delivery to cancer cells in vivo. To overcome this issue, we will generate a nanoparticle-based delivery platform targeting Acute Myeloid Leukemia (AML) and Metastatic Pancreatic Adenocarcinoma (PDAC), two types of cancer in which in vivo delivery of RNA-based therapeutics is notoriously inefficient. Using a phage display technique, we identify AML and PDAC targeting peptides in an unbiased fashion. The cancer-specific peptides will then be utilized to decorate lipid nanoparticles (LNPs) and allow the efficient delivery of our RNA-based oligonucleotides. Successful generation of such cancer-targeting nanoparticles may serve as a basis for future, oligonucleotide-based therapies. Furthermore, since receptor expression levels may differ dramatically among patients, we could tailor the specific targeting peptides to individual patients thereby increasing the precision and specificity of this therapy.