IP Library › Granted Patent US 12,324,818
Granted Patent B2
US 12,324,818 · App. 18/541,448 · Granted Jun 10, 2025

Generation of alveolar epithelial type 1 (AT1) cells

Inventors: Claire Burgess (Boston, MA); Darrell Kotton (Newton, MA)
A61K35/42C12N5/0688C12N15/86C12N2500/90C12N2501/11C12N2501/117C12N2501/119C12N2501/727C12N2513/00C12N2740/15043
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Quick Facts
Patent No.
US 12,324,818
App. No.
18/541,448
Granted
Jun 10, 2025
Kind
B2
Abstract

The technology described herein is directed to methods of producing or differentiating AT1 cells, and AT1 cells made by the methods described herein.

Claims (26)

1. A method comprising culturing at least one alveolar epithelial cell type II (AT2) cell and/or lung epithelial progenitor cell in a medium comprising a Large Tumor Suppressor Kinase (LATS) inhibitor;

wherein said culturing results in the differentiation of the at least one AT2 cell and/or lung epithelial progenitor cell to an alveolar epithelial cell type I (AT1) cell.

2. The method of claim 1 , wherein the medium is a complete serum free defined medium.

3. The method of claim 1 , wherein the LATS inhibitor is selected from the group consisting of:

LATS-IN-1 (TRULI; N-(3-benzylthiazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide); GA-017; and TDI-011536.

4. The method of claim 1 , wherein the medium does not comprise, or the at least one AT2 cell and/or lung epithelial progenitor cell is not in contact with, CHIR99021 and/or keratinocyte growth factor (KGF) protein.

5. The method of claim 1 , wherein the medium does not comprise, or the at least one AT2 cell and/or lung epithelial progenitor cell is not in contact with, ectopic epidermal growth factor (EGF) protein and/or ectopic fibroblast growth factor 10 (FGF10) protein.

6. The method of claim 1 , wherein the medium further comprises, or the at least one AT2 cell and/or lung epithelial progenitor cell is further contacted with, ectopic epidermal growth factor (EGF) protein and/or ectopic fibroblast growth factor 10 (FGF10) protein.

7. The method of claim 1 , whereby the culturing at least one AT2 cell and/or lung epithelial progenitor cell in a medium comprising a LATS inhibitor induces YAP signaling.

8. The method of claim 1 , wherein the at least one AT2 cell is a human AT2 cell, a primary AT2 cell, or an induced AT2 cell; and/or

the at least one lung epithelial progenitor cell is a human lung epithelial progenitor cell; a primary lung epithelial progenitor cell; or an induced lung epithelial progenitor cell.

9. The method of claim 1 , further comprising contacting the at least one AT2 cell and/or lung epithelial progenitor cell, or a cell produced by the method, with:

a nucleic acid encoding a reporter protein;

a virus;

smoke; and/or

Transforming Growth Factor Beta (TGFB) and/or bleomycin.

10. The method of claim 1 , wherein the at least one AT2 cell and/or lung epithelial progenitor cell comprises a pulmonary fibrosis (PF) inducing mutation.

11. The method of claim 1 , further comprising inducing ectopic Yes Associated Protein (YAP) expression in at least one AT2 cell and/or lung epithelial progenitor cell.

12. The method of claim 11 , wherein the YAP comprises:

mutation of the serine of at least one HXRXXS consensus sequence;

mutation of the serine of at least one HXRXXS consensus sequence to alanine;

mutation of the serine of every HXRXXS consensus sequence;

mutation of the serine of every HXRXXS consensus sequence to alanine;

mutation of each serine corresponding to S61, S109, S127, S164, and S397 of SEQ ID NO: 1; or

mutation of each serine corresponding to S61, S109, S127, S164, and S397 of SEQ ID NO: 1 to alanine.

13. The method of claim 11 , wherein inducing comprises contacting the at least one AT2 cell and/or lung epithelial progenitor cell with an expression vector encoding a YAP protein.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 16, 2024
From: BURGESS, CLAIRE; KOTTON, DARRELL
To: TRUSTEES OF BOSTON UNIVERSITY
Reel/Frame 067118/0748 →
CONFIRMATORY LICENSE Recorded Jan 9, 2024
From: BOSTON UNIVERSITY MEDICAL CAMPUS
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066071/0673 →
Continuity (2)
Provisional Application 63434299 · Dec 21, 2022
Related Publication 20240261337A1 · Aug 8, 2024
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