Compositions and methods for organ specific delivery of nucleic acids

Compositions and methods for organ specific delivery of nucleic acids

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions for use in a method for delivery of a gene or transcript editing composition to an organ or cell therein assembled with a selective organ targeting (SORT) lipid composition, wherein the SORT lipid composition comprises (1) an ionisable cationic lipid; and (2) a permanently cationic SORT lipid; and wherein the method comprises contacting said organ or said cell therein with said composition, thereby providing a modified expression profile of a target gene or transcript in said organ or said cell therein as compared to that achieved absent said SORT lipid. The composition is preferentially a lipid nanoparticle delivering clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) editing compositions to a target organ, preferably the lung(s), the liver, the lymph node(s), or the spleen. The CRISPR associated editing composition may comprise an enzyme, preferably a CRISPR nuclease (preferably Cas9). The permanently cationic ...

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ, in some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions, for use in a method of preferential delivery of a therapeutic agent to a non-liver organ or non-liver cell in a subject, comprising: the therapeutic agent; and a lipid nanoparticle comprising: (1) a selective organ targeting (SORT) compound; (2) an ionisable cationic lipid; (3) and optionally, a phospholipid; wherein the composition delivers a greater amount of, or provides a greater amount of activity of, the therapeutic agent in the non-liver organ or cell in the subject compared to that achieved absent the SORT lipid. The compositions may also comprise a polyethylene glycol-conjugated (PEGylated) lipid (e.g. DMG-PEG) and also optionally a steroid, preferably cholesterol. The non-liver organ is preferably the lung(s), the liver, the lymph node(s), or the spleen. The therapeutic agent may comprise a nucleic acid. The SORT compound is preferably a permanently cationic lipid comprising a quaternary ammonium ion (e.g. DOTAP, 1,2-Dioleoyl-3-trimethylammonium ...

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions for use in a method for delivery of a gene or transcript editing composition to an organ or cell therein assembled with a selective organ targeting (SORT) lipid composition, wherein the SORT lipid composition comprises (1) an ionisable cationic lipid; and (2) a zwitterionic SORT lipid or an anionic SORT lipid; and wherein the method comprises contacting said organ or said cell therein with said composition, thereby providing a modified expression profile of a target gene or transcript in said organ or said cell therein as compared to that achieved absent said SORT lipid. The composition is preferentially a lipid nanoparticle delivering clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) editing compositions to a target organ, preferably the lung(s), the liver, the lymph node(s), or the spleen. The CRISPR associated editing composition may comprise an enzyme, preferably a CRISPR nuclease (preferably Cas9). The SORT ...

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions comprising a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) editing composition; and a lipid nanoparticle composition comprising: (1) a selective organ targeting (SORT) compound; (2) an ionisable cationic lipid; (3) optionally, a phospholipid; (4) optionally, a polyethylene glycol-conjugated (PEGylated) lipid; and (5) optionally, a steroid; wherein the composition preferentially delivers the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) editing composition to a target organ, preferably the lung(s), the liver, the lymph node(s), or the spleen. The CRISPR associated editing composition may comprise a CRISPR nuclease (preferably Cas9, and also optionally with a mRNA and a sgRNA), a single guide RNA (sgRNA), a CRISPR-RNA, or a trans-activating RNA. The SORT compound is preferably a permanently cationic lipid comprising a quaternary ammonium ion (e.g. DOTAP, 1,2-Dioleoyl-3- ...