Cell lines and their use in encapsulated cell biodelivery
Inventors
Kusk, Philip • Wahlberg, Lars Ulrik
Assignees
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Publication Number
US-12396957-B2
Publication Date
2025-08-26
Expiration Date
Abstract
The present invention relates to generation of cell lines expressing recombinant proteins for use in naked and encapsulated cell biodelivery of secreted therapeutic molecules. In one embodiment the cell line is human. In another aspect of the invention the transposon system is used for generating a cell line for secretion of a biologically active polypeptide.
Core Innovation
The invention relates to a capsule for delivery of a secreted biologically active compound to a subject. The capsule includes a biocompatible outer membrane and an inner core comprising monoclonal cells, and the monoclonal cells comprise a heterologous expression construct that includes a structural gene coding for siRNA contributing to the generation of a biologically active secreted compound in the cells.
The structural gene is located between two inverted repeats, IR/DR, which are substrates for a transposase or other integrases. The monoclonal cells maintain a high and stable expression level of the siRNA absent the presence of a selective pressure, compared to the same cells generated without a transposase.
The capsule has a thickness of the outer membrane between 2 and 200 microns, a volume between 1 μL and 5 μL, and contains less than 10^3 monoclonal cells. The system is directed to delivery of a secreted biologically active compound using monoclonal cells with an siRNA-generating heterologous construct and long-term high and stable siRNA expression without selective pressure.
Claims Coverage
The partial content identifies one independent claim. It combines capsule geometry and cell number limits with the genetic arrangement and expression behavior defined by inverted repeats and transposase or integrases to maintain stable siRNA expression without selective pressure.
Capsule architecture with biocompatible outer membrane and inner core
A capsule comprising a biocompatible outer membrane and an inner core.
Monoclonal cells with heterologous siRNA-generating structural gene
The inner core comprising monoclonal cells, the monoclonal cells comprising a heterologous expression construct comprising a structural gene coding for siRNA contributing to the generation in the cells of a biologically active secreted compound.
Structural gene integration between inverted repeats for transposase/integrases
The gene being located between two inverted repeats, IR/DR, which are substrates for a transposase or other integrases.
High and stable siRNA expression absent selective pressure
Monoclonal cells maintaining a high and stable expression level of the siRNA absent the presence of a selective pressure compared to the same cells generated without a transposase.
Outer membrane thickness and capsule volume constraints
The thickness of the outer membrane is between 2 and 200 microns, and the capsule has a volume between 1 μL and 5 μL.
Limited monoclonal cell count in the capsule
The capsule contains less than 10^3 monoclonal cells.
Claim coverage is centered on an encapsulated biodelivery capsule that houses monoclonal cells carrying a heterologous siRNA structural gene integrated between IR/DR sequences for transposase or integrases, thereby maintaining high and stable siRNA expression without selective pressure, while also limiting capsule dimensions and cell number.
Stated Advantages
High and stable expression level of the siRNA absent the presence of a selective pressure, compared to the same cells generated without a transposase.
Documented Applications
Delivery of secreted biologically active polypeptides from SB-engineered ARPE-19 cells, including stable secretion of neuropeptides (galanin) and growth factors (NGF).
Implantation into animal brain regions, including hippocampus implantation in minipigs and striatum implantation in rats.
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