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Targeted delivery of therapeutic proteins bioencapsulated in plant cells to cell types of interest for the treatment of disease

A plant cell, therapeutic technology for animal/human proteins, receptors/cell surface antigens/cell surface determinants, mammalian proteins, etc.

Inactive Publication Date: 2018-10-23
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, T cells are only able to recognize peptides displayed by MHC class I and II molecules on the surface of APCs

Method used

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  • Targeted delivery of therapeutic proteins bioencapsulated in plant cells to cell types of interest for the treatment of disease
  • Targeted delivery of therapeutic proteins bioencapsulated in plant cells to cell types of interest for the treatment of disease
  • Targeted delivery of therapeutic proteins bioencapsulated in plant cells to cell types of interest for the treatment of disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0090] GFP fused with different tags is taken up by human cells

[0091] In this study, we investigated the oral administration of plant cells expressing GFP fused with different tags in chloroplasts and assessed cell targeting and its biodistribution. The PTD, DCpep, and CTB fusions were delivered across the intestinal epithelium using different routes, resulting in systemic delivery, biodistribution, and, perhaps most importantly, different uptake patterns by non-immune or immunoregulatory cells. These peptides can be used to deliver therapeutic proteins to serum, immunoregulatory cells, or specific tissues.

[0092] Three different transmucosal carriers were tested. The interaction of the CTB pentamer with the GM1 receptor has been well studied, as Figure 1A shown. The pentosan structure of the GM1 receptor interacts with the amino acids of CTB through hydrogen bonds [38]. In contrast, PTD ( Figure 1A ) or DCpep ( Figure 1A) mechanism of the structure shown has not...

Embodiment II

[0195] The uptake of GFP fused with different tags as follows was assessed in additional human cell lines: CTB-GFP, PTD-GFP, PG1-GFP and RC101-GFP

[0196] To expand the cell types that can be successfully targeted using the protein therapeutics described here, we evaluated the use of human somatic and stem cell lines. To generate targeted delivery of therapeutic proteins to benign and malignant tissues, six cell lines were selected. These cell lines include normal and cancer cell lines from human teeth, head and neck, and soft tissues. Three human stem cell lines were selected for the development of functional protein-based therapeutics for developmental defects and immature / stem cell tumors.

[0197] Figure 6A with 6B Results obtained from studies with different cell types and labels are shown. These human somatic cells include pancreatic cancer cells (PANC-1); human pancreatic ductal epithelial cells (HPDE); human head and neck squamous cell carcinoma cells (SCC-1); re...

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Abstract

Compositions and methods for producing therapeutic fusion proteins comprising targeting sequences directing the protein to cells or tissues of interest are disclosed.

Description

[0001] related application [0002] This application claims priority to US Provisional Application No. 62 / 256,053, filed November 16, 2015, the entire disclosure of which is incorporated herein by reference as if set forth in its entirety. [0003] The United States Government has rights to this invention, which was made with funding from the National Institutes of Health, grant numbers: R01 GM 63879, R01 HL 109442, and R01 HL 107904. technical field [0004] The present invention relates to the fields of transplastomic plants and low cost protein drug production and delivery. More specifically, the present invention provides plants comprising chloroplast-expressed transgenes encoding therapeutic proteins and peptides operably linked to targeting sequences that target The sequence directs the plant cell-encapsulated fusion protein to the target tissue. Background technique [0005] Several publications and patent documents are cited throughout the specification in order to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/05C12N15/11A61K38/28A61P3/10C07K14/555C07K14/56C07K14/565
CPCA61K38/00A61P3/10C07K14/70596C07K14/71C07K2319/00C07K2319/80C12N15/8257C12N15/8258A61K9/0053A61K9/48A61K36/00C07K14/28C07K14/435C07K14/4723C07K14/705C07K2319/60
Inventor 亨利·丹尼尔
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA