Table 2 Active targeting strategies for LNP-RNA therapeutics

Glu-urea-Lys PSMA

Androgen receptor

Prostate tumor

AR21 and AR25 siRNAs

[270]

MAdCAM-1-Fc protein

α4β7 integrin

Inflammatory gut-homing leukocytes

siRNA

[271]

aCD3 mAb (in vitro) aCD3 F(ab′)2 (in vivo)

Plasmalemma

Cd3

T cells in the tumor environment

mRNA

[272]

PV1

Caveolae

Lung

mRNA

[273]

Anti PECAM-1 (CD31) mAb

Lung endothelial cells

Lung

mRNA

[263]

DEC205 scFv

DEC205 + murine DCs

Spleen

siRNA

[274]

aCD4 mAb

CD4

T cell

mRNA

[275]

aCD5

Splenic T cells

Cardiac fibrosis

mRNA

[261]

pMHC1

Antigen-specific CD8⁺T cells

Pr8 influenza virus

mRNA

[265]

CH6 Aptamer

Osteoblast

Metabolic skeletal disorders associated with impaired bone formation (e.g. osteoporosis)

siRNA

[269]

Anti-VCAM-Ab (CD106)

VCAM1

Brain neutrophils/glioblastoma

mRNA

[276]

aCD177

C5a

Neutrophils

siRNA and ASOs

[277]

Anti-Ly6C antibodies by ASSET

IRF8 mRNA

Ly6C + inflammatory leukocytes/DSS colitis

siRNA

[278]

aEGFR

EGFR

Tumor

Cas9-mRNA/ sgRNA

[279]

BP

Monocytes in bone marrow

Bone

mRNA

[280]

Mannose

Langerhans cells, dermal DCs, and resident DCs in the skin-draining lymph node

Influenza virus

SAM

[281]

Mannose

Hepatocytes and LSEC

Liver

mRNA

[256]

α-Galactosyl ceramide

Invariant natural killer T cells

Tumor

mRNA

[282]

Mannose

DCs in lymph node

Tumor

mRNA and siRNA

[283]

Tri-GalNAc

ASGPR

Hepatocytes in liver

siRNA

[284]

Cyclic peptide pPB

PDGFR β

Hepatic stellate cells in liver

siRNA

[285]

Mannan

Mannose receptor

DCs

SAM

[286]

Anti-β7-mAb

Integrin β7

T-lymphocytes

siRNA

[287]

Angiopep-2

LRP1

Brain

siRNA

[288]

RVG-9r

nAChR

Brain

siRNA

[289]

Azide-modified antibodies (CLIP approach)

LYVE1

LECs

siRNA

[290]

Doxorubicin

Bcl-2

Tumor

siRNA

[291]

LDV

α4β1 integrin

Leukemic cells

siRNA

[292]

Peptide ligands

PRs

Neural retina

mRNA

[222]

Transferrin

Transferrin receptor

Brain

miRNA

[293]

PD-L1

PD-L1

Breast cancer

mRNA

[294]

Anisamide

Sigma receptor of HSCs

Liver fibrosis

siRNA

[295]