Nanomedicine approaches for treatment of hematologic and oncologic malignancies

Table 3 Summary of nanomedicines based on nucleic acids

Name	Category	Structure	Mode of action	Status
ASO	Inhibition of translation of cancer or angiogenesis associated proteins	Synthetic ssDNA or ssRNA oligos complementary to mRNA of interest	Rnase H mediated mRNA degradation	In clinical trials; LNP-based anti-Grb2 ASOs for leukemia[70] and solid tumors[71]; LNP-based anti-Bcl-2 ASOs for advanced lymphoid malignancies[72]
siRNA	Inhibition of translation of cancer or angiogenesis associated proteins	Synthetic dsRNA oligos complementary to mRNA of interest	Dicer induces cleavage of dsRNA and RNA-induced silencing complex mRNA degradation	In clinical trials; Polymeric anti-KRAS siRNAs for pancreatic ductal adenocarcinoma[78]; LNP based anti-PKN3 siRNAs in patients with advanced solid tumors[79]; LNP based anti-KSP and anti-VEGF-A siRNAs in patients with solid tumors[80,81]; LNP based anti-PLK1 siRNAs in patients with solid tumors[82]
saRNA	Forced exogenous gene expression	Synthetic dsRNA oligos complementary to mRNA of interest	Target gene promoters to induce transcriptional gene activation	In clinical trials; LNP based formulations for treatment of hepatocellular carcinoma[84] and advanced solid tumors[85]
miRNA mimics	Regulation of post- transcriptional mRNA expression	Chemically modified dsRNA molecules designed to mimic endogenous microRNAs	Translational repression and gene silencing	Currently only in basic research[87]
mRNA vaccines	Forced exogenous antigen expression	Synthetic mRNA	Induction of immune response against cancer cells	In clinical trials; LNP-based mRNA vaccines encoding known tumor-specific antigens are being investigated in early phase clinical trials in patients with HPV-driven squamous cell carcinoma[90], melanoma[90], ovarian[92], pancreatic, lung, and colorectal cancer[93]; Personalized vaccines based on patient specific neo-antigens are being assessed clinically for the treatment of melanoma[95] and breast cancer[96]

ASO: Antisense oligonucleotides; saRNA: Small activating RNA; siRNA: Small interfering RNAs; LNP: Lipid nanoparticle.