Nucleic acid delivery for therapeutic applications

Akash Gupta; Jason L Andresen; Rajith S Manan; Robert Langer

doi:10.1016/j.addr.2021.113834

Nucleic acid delivery for therapeutic applications

Adv Drug Deliv Rev. 2021 Nov:178:113834. doi: 10.1016/j.addr.2021.113834. Epub 2021 Sep 4.

Authors

Akash Gupta¹, Jason L Andresen², Rajith S Manan³, Robert Langer⁴

Affiliations

¹ David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.
² David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴ David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: rlanger@mit.edu.

PMID: 34492233
DOI: 10.1016/j.addr.2021.113834

Abstract

Recent medical advances have exploited the ability to address a given disease at the underlying level of transcription and translation. These treatment paradigms utilize nucleic acids - including short interfering RNA (siRNA), microRNA (miRNA), antisense oligonucleotides (ASO), and messenger RNA (mRNA) - to achieve a desired outcome ranging from gene knockdown to induced expression of a selected target protein. Towards this end, numerous strategies for encapsulation or stabilization of various nucleic acid structures have been developed in order to achieve intracellular delivery. In this review, we discuss several therapeutic applications of nucleic acids directed towards specific diseases and tissues of interest, in particular highlighting recent technologies which have reached late-stage clinical trials and received FDA approval.

Keywords: Biomaterials; COVID-19; Cancer; Genetic disease; Nucleic acid (oligonucleotide) delivery; Therapeutics; Vaccines.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
COVID-19 / genetics
COVID-19 / metabolism
COVID-19 / therapy
Clinical Trials as Topic / methods
Drug Approval
Drug Delivery Systems / methods
Drug Delivery Systems / trends*
Gene Transfer Techniques / trends*
Hepatitis / genetics
Hepatitis / metabolism
Hepatitis / therapy
Humans
MicroRNAs / administration & dosage
MicroRNAs / genetics
MicroRNAs / metabolism
Neoplasms / genetics
Neoplasms / metabolism
Neoplasms / therapy
Nucleic Acids / administration & dosage*
Nucleic Acids / genetics*
Nucleic Acids / metabolism
Oligonucleotides, Antisense / administration & dosage*
Oligonucleotides, Antisense / genetics*
Oligonucleotides, Antisense / metabolism
RNA, Messenger / administration & dosage
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / administration & dosage
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism

Substances

MicroRNAs
Nucleic Acids
Oligonucleotides, Antisense
RNA, Messenger
RNA, Small Interfering

Grants and funding

R01 EB000244/EB/NIBIB NIH HHS/United States