Table 1.

Drug delivery systems (DDS) for nucleic acid drugs, including those in clinical trials.

Carrier	Molecule	Target	Disease	Approved	Clinical Trial		References
					Phase (Approved)	ClinicalTrials.gov Identifier
Protamine Protamine	ASO ASO	c-myc HIV-1	Histiocytic lymphoma cell HIV-AIDS	- -	- -	- -	[49] [50]
PEI PEI	DNA vaccine RGT100	- RIG-1	B-cell non-Hodgkin’s lymphoma Advanced metastatic solid tumor	- -	I/ongoing I/completed	ISRCTN31090206 NCT03739138	[51] [52]
Anionic dendrimer	ASO	EGFR	Epidermoid carcinoma	-	-	-	[21]
LNP Lipoplex Lipoplex Liposome PSL	siRNA siRNA mRNA vaccine siRNA DNA	TTR PKN3 - GSTP -	hATTR amyloidosis advanced pancreatic cancer (cancer vaccine) Non-small cell lung cancer (brain targeting)	Yes, patisiran - - - -	(2018) II/completed II/recruiting I/recruiting -	- NCT01808638 NCT04526899 NCT03819387 -	[10,38,39] [14,15,16] [41,42] [40] [22]
EDV	miR-16 mimic	EGFR	Malignant pleural mesothelioma Non-small cell lung cancer	-	I/completed	NCT02369198	[53,54]
LODER™	siRNA	K-ras G12D	Pancreatic cancer	-	II/recruitig	NCT01676259	[17,18,19]
GalNAc GalNAc Cholesterol Folic acid (FA) CPP	siRNA siRNA siRNA microRNA PMO	ALAS1 HAO1 ApoB - c-myc	Acute hepatic porphyria Primary hyperoxaluria type 1 (liver targeting) Breast cancer (enhance PMO’s PK)	Yes, givosiran Yes, lumasiran - - -	(2019) (2020) - - -	- - - - -	[11] [13] [55,56] [57] [58]
Anti-body Antibody Fab’ + protamine	siRNA dsASO siRNA	STAT3 DRR/FAM107A c-myc, VEGF	Lewis-y positive cancer cell Glioblastoma stem cell HIV/AIDS	- - -	- - -	- - -	[44] [46] [43]
Antibody + exosome	ASO	miR-21	Adenosquamous carcinoma	-	-	-	[27]
Exosome Exosome Exosome MSC-derived exosome Exosome + FA + PEI	siRNA hsiRNA siRNA siRNA siRNA/plasmid	GAPDH Huntintin S100A4 K-ras G12D K-ras/p53	Alzheimer’s disease Huntington’s disease TNBC Pancreatic cancer Lung cancer	- - - - -	- - - I/recruiting -	- - - NCT03608631 -	[30] [32] [33] [35,36] [34]