Table 3.

Block copolymer‐based systems to deliver mRNA

Polymer component a)	Molecular weight	Preparation method	Average size [nm]	Zeta potential [mV]	Cation to RNA ratio	Design elements	Experimental application	Outcome b)	Refs.
PEG‐P(Asp(DET))	22 kDa	Self‐assembly in 10 × 10‐3 m HEPES buffer	50	Not reported	N/P = 8	Endosomal escape	Intrathecal	Expression in central nervous system	[94a]
PEG‐P(Asp(DET)) P(DMAEMA‐co‐OEGMA)	22 kDa 54 kDa	Self‐assembly in 10 × 10‐3 m HEPES buffer Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.3)	Not reported	Not reported 0.071 ± 0.159	N/P = 3	N/P = 3	Intranasal	Local expression	[100]
			50		N/P = 3	N/P = 3	Hydrodynamic injection	Liver	[101]
		Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.3) Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.4)	50 65 ± 5		N/P = 8	N/P = 8	Intra‐articular	Local expression	[102]
				Not reported	N/P = 3	N/P = 3	Intracerebral	Genome editing in brain	[103]
		Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.4) Self‐assembly in HEPES buffered saline (HBS, 150 × 10‐3 m NaCl, 10 × 10‐3 m HEPES, pH 7.4)	Not reported	Not reported 37 ± 15	N/P = 3	N/P = 3	Intraspinal injections	Spinal cord injury treatment	[104]
	20–22 kDa		37		N/P  10–40	PEGylation	Intracellular	BEAS‐2B cells	[105]
PEGMA‐p(DMAEMA‐co‐BMA))	61.7 kDa	Self‐assembly in nuclease‐free water	86 ± 16	12.4 ± 0.7	N/P = 3	Endosomal escape	Intracellular	T cells	[106]
P(MEO3MA)‐b‐P(H2N‐Cys‐MA)	69.3 kDa	Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.4)	87	Not reported	N/P = 5	Redox‐responsive by disulfide bonds	Intracellular	RAW macrophages and 3T3 fibroblasts	[107]
P(EtOx)‐P(EI)	45 kDa for mRNA, and 72 kDa	Self‐assembly in DMEM	80–450	−5–2	7000 (molar ratio)	Molar mass and charge density optimized	Intracellular	HEK 293T cells	[81]
PEG‐P(Asp(TEP))‐Chol	34 kDa	Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.3)	55	Not reported	N/P = 8	Hydrophobicity and endosomal escape	i.v.	BxPC‐3 pancreatic tumor	[110]
PEG‐P(Asp(DET))‐Chol	25 kDa	Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.4)	60–65	1.1	N/P = 3	Chol (+)‐OligoRNA	Intratracheal	Local expression	[112a]
PEG‐PLys	19 kDa	Self‐assembly in 10 × 10‐3 m HEPES buffer (pH 7.4) Mixing polymer solution (10 × 10‐3 m HEPES buffer, pH 3.5) with mRNA solution (10 × 10‐3 m HEPES buffer, pH 7.4)	100	Not reported	N/P = 2	mRNA bundling	Intracerebral	Improved blood circulation Local expression	[112b]
PEG‐PGBA	22 kDa		56	1.1	N/P = 3	Flexible polycation	Intranasal	Improved blood circulation; Local expression	[115]
PEG‐PGMG	18 kDa		62	0.90	N/P = 3	Multivalent interactions from guanidine	Intracellular	HuH‐7 cells	[116]
PEG‐PGTyr	26 kDa		75	Not reported	N/P = 3	π–π stacking	i.v. and i.m.	Improved blood circulation Local expression	[117]
cRGD‐PEG/PNIPAM‐PLys(SH)	12 kDa/5 kDa		59 ± 2	1.89 ± 0.28	N/P  = 1.5	Redox‐responsive crosslinking; thermo‐responsive	i.v.	U‐87 glioma tumor	[119]
PEG‐PLys(AMP)	23 kDa		53 ± 2	−1.23 ± 0.4	N/P = 2	Redox‐responsive crosslinking	Intracellular	HuH‐7 cells	[120]
PEG‐PAsp(DET/FPBA)‐Chol, PEG‐PAsp(DET/GlcAm)‐Chol	22 kDa		70–90	−2.5 ± 0.9	N/P  = 1.5	ATP‐responsive crosslinking; Chol (+)‐OligoRNA	Intracellular	Improved blood circulation	[112c]
PEG‐pLL(CAA)	20 kDa		94 ± 1	Not reported	Not reported	pH‐responsive crosslinking	Intratumoral	Improved expression in CT 26 tumors	[123]
PEG‐PAsp(DET/FPBA)	24 kDa		59–72	Not reported	N/P  = 1.5	ATP‐responsive crosslinking	Intratracheal	Local expression	[112d]

^a) The full name of polymers can be found in the main text;

^b) BEAS‐2B: human non‐tumorigenic lung epithelial cell line; 3T3: mouse embryonic fibroblast cell line, HEK 293T: a stable clone derivative of the human embryonic kidney (HEK) 293 cell line; HuH‐7: hepatocyte‐derived carcinoma cell line.