RNA INTERFERENCE TARGET FOR TREATING AIDS

• US 20110243904A1
• Filed: 06/02/2008
• Published: 10/06/2011
• Est. Priority Date: 05/31/2007
• Status: Abandoned Application

• Current Assignee: Beijing Wantai Biological Pharmacy Enterprise Co.,Ltd., Xiamen University
• Original Assignee: Beijing Wantai Biological Pharmacy Enterprise Co.,Ltd., Xiamen University
• Inventors: Zhang, Tao, Zhang, Jun, Zhang, Yali, Cheng, Tong, Xia, Ningshao, Miao, Ji
• Application Number:
  US12/602,005
• Publication Number:
  US 20110243904A1
• Time in Patent Office: Days
• US Class Current: 424/93.21
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C12N 15/1132 against retroviridae, e.g. HIV
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/12 catalytic nucleic acids, e.g. ribozymes
• CPC Class Codes: C12N 2310/14 interfering N.A.

Abstract

The present invention relates to RNA interference target sequence targeting HIV for the treatment of AIDS. Based on the target sequence, recombinant expression vectors, packaging vectors and cells were constructed, which express a siRNA and/or a miRNA and/or a ribozyme and/or an antisense oligonucleotide targeting HIV. Also provided is the use of the recombinant expression vectors, packaging vectors and recombinant cells in the manufacture of a medicament for the treatment of AIDS.

Claims

1. A RNA interference target sequence targeting HIV, which is selected from:

(1) a sequence set forth in any one of SEQ ID NOs;

1-32, or

(2) a sequence that has at least 70%, preferably at least 80%, 85%, 90%, 95%, 98% or higher identity to the sequence defined in (1), or

(3) a nucleotide sequence that can hybridize with the sequence defined in (1) under stringent conditions or highly stringent conditions, or

(4) a nucleotide sequence that is different from the sequence defined in (1) by only 1-3, preferably 1-2, more preferably 1 nucleotide(s), or

(5) a fragment or a complementary sequence of any of the sequences referred to above.

2. A nucleic acid construct or a vector, such as an expression vector, comprising the sequence according to claim 1.

3. A siRNA or a miRNA or a ribozyme or an antisense oligonucleotide obtained based on the RNA interference target sequence according to claim 1, which can inhibit the expression of the corresponding gene of HIV and/or the replication of HIV and/or the infection of HIV.

4. A recombinant expression vector which can express the siRNA or the miRNA or the ribozyme or the antisense oligonucleotide according to claim 3.

5. The recombinant expression vector according to claim 4, comprising a nucleic acid sequence encoding the siRNA or the miRNA or the ribozyme or the antisense oligonucleotide targeting HIV, wherein the encoding nucleic acid sequence is operably linked to an expression controlling sequence so that the siRNA or the miRNA or the ribozyme or the antisense oligonucleotide can be expressed in an animal cell, especially a mammalian cell, such as a human cell, preferably a HIV receptor cell and a stem cell.

6. The recombinant expression vector according to claim 4, which is a plasmid vector or a virus vector, such as a retrovirus vector, including a lentivirus vector.

8. An isolated cell transformed or transfected or transduced with the recombinant expression vector according to claim 4.

10. A modified cell, including an animal cell, such as a mammalian cell, preferably a human cell, preferably a HIV receptor cell and a stem cell, such as a CD4+cell and a CD34+cell, which can express or comprises the siRNA or the miRNA or the ribozyme or the antisense oligonucleotide according to claim 3.

11. The modified cell according to claim 10, which carries in its genome or outside of its genome an encoding nucleic acid sequence comprising the RNA interference target sequence according to claim 1, wherein the encoding nucleic acid sequence is operably linked to an expression-controlling sequence so that the siRNA or the miRNA or the ribozyme or the antisense oligonucleotide can be expressed in the cell, including an animal cell, such as a mammalian cell, preferably a human cell, preferably a HIV receptor cell and a stem cell, such as a CD4+cell and a CD34+cell.

12. A method for producing the cell according to any one of claims 8 and 10, comprising transforming or transfecting or transducing a cell, including an animal cell, such as a mammalian cell, preferably a human cell, preferably a HIV receptor cell and a stem cell, such as a CD4+cell and a CD34+cell, with the recombinant expression vector according to claim 4.

13. A combination of DNA sequences comprising or consisting of a first DNA sequence encoding a sense RNA segment and a second DNA sequence encoding an antisense RNA segment, wherein the sense RNA segment comprises a RNA sequence encoded by the target sequence according to claim 1, and the antisense RNA segment can form a double-stranded RNA with the sense RNA segment, and wherein the double-stranded RNA can suppress the expression of HIV gene and/or the replication of HIV and/or infection of HIV.

14. A small interference RNA (siRNA) comprising a sense RNA segment and an antisense RNA segment, wherein the sense RNA segment comprises a RNA sequence encoded by the target sequence according to claim 1, and the antisense RNA segment can form a double-stranded RNA with the sense RNA segment, and wherein the double-stranded RNA can suppress the expression of the corresponding gene of HIV and/or the replication of HIV and/or the infection of HIV.

16. A method for treating HIV infection or a HIV patient or inhibiting the replication or gene expression of HIV, comprising administering to a patient a therapeutically effective amount of:

the RNA interference target sequence according to claim 1, or

the nucleic acid construct or the vector according to claim 2, or

the siRNA or the miRNA or the ribozyme or the antisense oligonucleotide according to claim 3, or

the recombinant expression vector according to claim 4, or

the cell according to any one of claims 8 and 10, or

the siRNA according to claim 14.

7. (canceled)

9. (canceled)

15. (canceled)

17. (canceled)

18. (canceled)