1162069-33-1Relevant articles and documents
Receptor-Specific Delivery of Peptide Nucleic Acids Conjugated to Three Sequentially Linked N-Acetyl Galactosamine Moieties into Hepatocytes
Bhingardeve, Pramod,Madhanagopal, Bharath Raj,Naick, Hemanth,Jain, Prashant,Manoharan, Muthiah,Ganesh, Krishna
, p. 8812 - 8824 (2020)
Peptide nucleic acids (PNAs) are DNA analogs that bind with high affinity to DNA and RNA in a sequence-specific manner but have poor cell permeability, limiting use as therapeutic agents. The work described here is motivated by recent reports of efficient gene silencing specifically in hepatocytes by small interfering RNAs conjugated to triantennary N-acetyl galactosamine (GalNAc), the ligand recognized by the asialoglycoprotein receptor (ASGPR). PNAs conjugated to either triantennary GalNAc at the N-terminus (the branched architecture) or monomeric GalNAc moieties anchored at Cγ of three consecutive PNA monomers of N-(2-aminoethyl)glycine (aeg) scaffolds (the sequential architecture) were synthesized on the solid phase. These formed duplexes with complementary DNA and RNA as shown by UV and circular dichroism spectroscopy. The fluorescently labeled analogs of GalNAc-conjugated PNAs were internalized by HepG2 cells that express the ASGPR but were not taken up by HEK-293 cells that lack this receptor. The sequential conjugate was internalized about 13-fold more efficiently than the branched conjugate into HepG2 cells, as demonstrated by confocal microscopy. The results presented here highlight the potential significance of the architecture of GalNAc conjugation for efficient uptake by target liver cells and indicate that GalNAc-conjugated PNAs have possible therapeutic applications.
TARGETED THERAPEUTIC NUCLEOSIDES AND THEIR USE
-
Page/Page column 112, (2015/04/15)
Provided herein are compounds comprising one or more therapeutic nucleosides and one or more targeting groups. In certain embodiments, the compounds further comprise one or more oligonucleotides. In certain embodiments, a targeting group comprises one or more N-Acetylgalactosamine.
COMPOSITIONS AND METHODS FOR MODULATING COMPLEMENT FACTOR B EXPRESSION
-
Page/Page column 155, (2015/11/23)
The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with dysregulation of the complement alternative pathway by administering a Complement Factor B (CFB) specific inhibitor to a subject.
COMPOSITIONS AND METHODS FOR MODULATING GROWTH HORMONE RECEPTOR EXPRESSION
-
Page/Page column 146-147, (2015/11/23)
The present embodiments provide methods, compounds, and compositions for treating, preventing, ameliorating a disease associated with excess growth hormone using antisense compounds oligonucleotides targeted to growth hormone receptor (GHR).
COMPOSITIONS AND METHODS FOR MODULATING ANGIOPOIETIN-LIKE 3 EXPRESSION
-
Page/Page column 180, (2015/11/23)
Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.
CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE
-
Page/Page column 512, (2014/11/13)
Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.
COMPOSITIONS AND METHODS FOR MODULATION OF TARGET NUCLEIC ACIDS
-
Page/Page column 142, (2015/01/07)
The present disclosure pertains generally to chemically-modified oligonucleotides for use in research, diagnostics, and/or therapeutics. In certain embodiments, the present disclosure describes compounds and methods for the modulation of a target nucleic
