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US 12,558,437 B2Granted
Compositions and methods for epigenetic regulation of HBV gene expression
AssigneenChroma Bio, Inc.
InventorsAron Brandon Jaffe, Noorussahar Abubucker, Yesseinia Anglero-Rodriguez, Vic Myer, Angelo Leone Lombardo, Martino Alfredo Cappelluti
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Abstract
This invention relates to compositions, methods, strategies, and treatment modalities related to the epigenetic modification of hepatitis B virus (HBV) genes.
Claims20
A method, comprising administering an epigenetic editing system to a subject, wherein the subject has detectable levels of HBV DNA, HBsAg, and/or HBeAg in the serum of the subject,
- wherein the epigenetic editing system comprises
- a) a fusion protein, or a nucleic acid encoding the fusion protein, comprising
- i) a first dCas9 protein domain,
- ii) a first DNMT domain,
- and
- iii) an epigenetic repression domain, wherein the epigenetic repression domain is a KRAB domain
- wherein the dCas9 protein domain binds a first target region of an HBV genome located within a region of the HBV genome comprising nucleotides 1000-2448, and
- wherein the first target region overlaps with CpG Island II (CGI II) of the HBV genome, and
- b) a first guide RNA (gRNA) comprising a region complementary to a strand of the first target region, or one or more other nucleic acid molecules encoding the same;
- wherein administering the epigenetic editing system results in a reduction of the level of HBV DNA, the level of HBsAg, and/or the level of HBeAg in the serum of the subject, wherein the reduction is maintained for at least 35 days after the administering.
7 more elements
A method, comprising administering an epigenetic editing system to a subject, wherein the subject has detectable levels of HBV DNA, HBsAg, and/or HBeAg in the serum of the subject,
- wherein the epigenetic editing system comprises
- a) a fusion protein, or a nucleic acid encoding the fusion protein, comprising
- i) a first dCas9 protein domain
- ii) a first DNMT domain
- and
- iii) an epigenetic repression domain, wherein the epigenetic repression domain is a KRAB domain,
- wherein the first dCas9 protein domain binds a first target region of an HBV genome located within a region of the HBV genome comprising nucleotides 1000-2448, and
- wherein the first target region comprises nucleotides within 500 bps of a transcription start site of an HBx RNA, and
- b) a first guide RNA (gRNA) comprising a region complementary to a strand of the first target region, or one or more other nucleic acid molecules encoding the same;
- wherein administering the epigenetic editing system results in a reduction of the level of HBV DNA, the level of HBsAg, and/or the level of HBeAg in the serum of the subject, wherein the reduction is maintained for at least 35 days after the administering.
7 more elements
Dependencies are inferred from the claim text.