TY - JOUR
T1 - Targeted lipid nanoparticles for RNA therapeutics and immunomodulation in leukocytes
AU - Veiga, Nuphar
AU - Diesendruck, Yael
AU - Peer, Dan
N1 - Funding Information:
This work was supported in part by grants from The Dotan Center for Hemato-Oncology at Tel Aviv University; The Lewis Trust for Blood Cancer; and by the ERC grant LeukoTheranostics (# 647410) awarded to DP.
Funding Information:
N.V. thanks the Marian Gertner Institute of Medical Nanosystems, the Dan David Fellowship Award, the Bruce and Ruth Rappaport Foundation and Iafa Keidar Prize for all their support.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/1
Y1 - 2020/1
N2 - Abnormalities in leukocytes' function are associated with many immune related disorders, such as cancer, autoimmunity and susceptibility to infectious diseases. Recent developments in Genome-wide-association-studies give rise to new opportunities for novel therapeutics. RNA-based modalities, that allow a selective genetic manipulation in vivo, are powerful tools for personalized medicine, enabling downregulation or expression of relevant proteins. Yet, RNA-based therapeutics requires a delivery modality to facilitate the stability, uptake and intracellular release of the RNA molecules. The use of lipid nanoparticles as a drug delivery approach improves the payloads' stability, pharmacokinetics, bio-distribution and therapeutic benefit while reducing side effects. Moreover, a wide variety of targeting moieties allow a precise and modular manipulation of gene expression, together with the ability to identify and selectively affect disease-relevant leukocytes-subsets. Altogether, RNA-based therapeutics, targeting leukocytes subsets, is believed to be one of the most promising therapeutic concepts of the near future, addressing pressing issues in cancer and inflammation heterogeneity.
AB - Abnormalities in leukocytes' function are associated with many immune related disorders, such as cancer, autoimmunity and susceptibility to infectious diseases. Recent developments in Genome-wide-association-studies give rise to new opportunities for novel therapeutics. RNA-based modalities, that allow a selective genetic manipulation in vivo, are powerful tools for personalized medicine, enabling downregulation or expression of relevant proteins. Yet, RNA-based therapeutics requires a delivery modality to facilitate the stability, uptake and intracellular release of the RNA molecules. The use of lipid nanoparticles as a drug delivery approach improves the payloads' stability, pharmacokinetics, bio-distribution and therapeutic benefit while reducing side effects. Moreover, a wide variety of targeting moieties allow a precise and modular manipulation of gene expression, together with the ability to identify and selectively affect disease-relevant leukocytes-subsets. Altogether, RNA-based therapeutics, targeting leukocytes subsets, is believed to be one of the most promising therapeutic concepts of the near future, addressing pressing issues in cancer and inflammation heterogeneity.
KW - Drug delivery
KW - Immunomodulation
KW - LNPs
KW - Leukocytes
KW - Nanoparticles
KW - Reprogramming
KW - mRNA therapeutics
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U2 - 10.1016/j.addr.2020.04.002
DO - 10.1016/j.addr.2020.04.002
M3 - Review article
C2 - 32298783
AN - SCOPUS:85083339864
SN - 0169-409X
VL - 159
SP - 364
EP - 376
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
ER -