IP Library › Granted Patent US 12,410,445
Granted Patent B2
US 12,410,445 · App. 17/701,488 · Granted Sep 9, 2025

Vector system for expressing regulatory RNA

Inventors: Tyler Lahusen (Rockville, MD); Lingzhi Xiao (Rockville, MD); Charles David Pauza (Rockville, MD)
Assignee: American Gene Technologies International Inc.
C12N15/86C12N15/113C12N2310/14C12N2740/15023C12N2740/15043
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Quick Facts
Patent No.
US 12,410,445
App. No.
17/701,488
Granted
Sep 9, 2025
Kind
B2
Abstract

Viral vectors, lentiviral particles, and modified cells are disclosed. They encode or express a small RNA capable of targeting the KIF11 gene. In embodiments, the viral vectors and lentiviral particles further comprise and a KIF11 gene whose non-coding region has been modified such that it is resistant to activity by the small RNA.

Claims (27)

1. A modified mesenchymal stem cell comprising a mesenchymal stem cell infected with a lentiviral particle, wherein the lentiviral particle comprises:

an envelope protein capable of infecting the mesenchymal stem cell; and

a first nucleotide sequence encoding a small RNA capable of binding a non-coding region of a host copy of KIF11, wherein the first nucleotide sequence encoding a small RNA is present in the modified mesenchymal stem cell at between about 1 and about 10 copies per cell.

2. The modified mesenchymal stem cell of claim 1 , wherein the non-coding region of the host copy of KIF11 is a 3′ untranslated region or a 5′ untranslated region.

3. A method of producing a modified mesenchymal stem cell, the method comprising: infecting a mesenchymal stem cell with an effective amount of a lentiviral particle, wherein the lentiviral particle comprises:

an envelope protein capable of infecting the mesenchymal stem cell; and

a first nucleotide sequence encoding a small RNA capable of binding a non-coding region of a host copy of KIF11, wherein the first nucleotide sequence is present in the modified mesenchymal stem cell at between about 1 and about 10 copies per cell.

4. The method of claim 3 , wherein the non-coding region of the host copy of KIF11 is a 3′ untranslated region or a 5′ untranslated region.

5. A method of treating cancer in a subject, the method comprising administering a therapeutically-effective amount of the modified mesenchymal stem cell of claim 1 to the subject.

6. The method of claim 5 , wherein the modified mesenchymal stem cell is allogeneic to the subject.

7. The method of claim 5 , wherein the modified mesenchymal stem cell is autologous to the subject.

8. The method of claim 5 , wherein the cancer is selected from any one or more of a carcinoma, a sarcoma, a myeloma, a lymphoma, a mixed type, or a mixture of the foregoing.

9. A lentiviral particle produced by a packaging cell and capable of infecting a target cell, the lentiviral particle comprising:

an envelope protein capable of infecting the target cell; and

a first nucleotide sequence encoding a small RNA capable of binding a non-coding region of a host copy of KIF11,

wherein the non-coding region of the host copy of KIF11 is a 3′ untranslated region or a 5′ untranslated region,

wherein the lentiviral particle further comprises a second nucleotide sequence encoding a KIF11 gene or a variant thereof, wherein the KIF11 gene or the variant thereof lacks at least one sequence portion,

wherein the sequence portion is in a non-coding region of the KIF11 gene, and wherein the non-coding region of the KIF11 gene is in at least one of a 5′ untranslated region or a 3′ untranslated region, and

wherein the target cell is a mesenchymal stem cell.

10. A method of treating cancer in a subject, the method comprising administering a therapeutically effective amount of the lentiviral particle of claim 9 to the subject.

11. The method of claim 10 , wherein the cancer is selected from any one or more of a carcinoma, a sarcoma, a myeloma, a lymphoma, a mixed type, or a mixture of the foregoing.

12. The method of claim 10 , wherein the lentiviral particle is administered to the subject via an infected target cell.

13. The method of claim 12 , wherein the target cell comprises a somatic cell.

14. The method of claim 13 , wherein the somatic cell comprises a hepatocyte or a lymphocyte.

15. The method of claim 14 , wherein the somatic cell comprises a lymphocyte, wherein the lymphocyte comprises a tumor specific T cell.

16. The method of claim 12 , wherein the target cell comprises a stem cell.

17. The method of claim 16 , wherein the stem cell comprises an induced pluripotent stem cell or a mesenchymal stem cell.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 22, 2023
From: LAHUSEN, TYLER; XIAO, LINGZHI; PAUZA, CHARLES DAVID
To: AMERICAN GENE TECHNOLOGIES INTERNATIONAL INC.
Reel/Frame 063066/0107 →
Continuity (3)
Continuation 17289653
Provisional Application 62755985 · Nov 5, 2018
Related Publication 20220372513A1 · Nov 24, 2022
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