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Fusosome compositions and uses thereof

A fusogenic agent and liposome technology, applied in the field of fusogenic liposome composition and its application, can solve difficult problems such as delivery of biological agents

Pending Publication Date: 2021-02-12
FLAGSHIP PIONEERING INNOVATIONS V INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, delivery of large biologics into cells is difficult as the plasma membrane acts as a barrier between the cell and the extracellular space

Method used

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  • Fusosome compositions and uses thereof
  • Fusosome compositions and uses thereof
  • Fusosome compositions and uses thereof

Examples

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example

[0980] The following examples are presented to aid in the understanding of the invention but are not intended and should not be construed as limiting its scope in any way.

example 1

[0981] Example 1. Analysis of non-target cells to test the specificity of retroviral nucleic acid delivery

[0982] This example describes the quantification of nucleic acids in non-target recipient cells by measuring vector copy number in single cells.

[0983] In one embodiment, the vector copy number in non-target cells of the treated mouse is similar to the vector copy number in those cells of the untreated mouse, eg, no vector or vector number similar to negative control levels. In one embodiment, the treated mice have a percentage of non-target cells containing the vector that is similar to those of untreated mice, eg, no cells or cell numbers similar to negative control levels.

[0984] In this example, the non-target recipient cells are CD11c+ cells. However, this protocol can be adapted to any cell type for which suitable surface markers are present and which can be isolated from a subject. It is worth noting that the method described in this paper can also be app...

example 2

[0988] Example 2. Analysis of Non-Target Cells to Test the Specificity of Exogenous Protein Agent Delivery

[0989] This example describes the quantification of exogenous agent expression in non-target recipient cells based on exogenous agent expression in single cells.

[0990] In one embodiment, the expression of the exogenous agent in the non-target cells of the treated mouse is similar to that of the untreated mouse. In one embodiment, treated mice have a similar percentage of non-target cells expressing the exogenous agent as untreated mice.

[0991] In this example, the non-target recipient cells are CD11c+ cells. However, this protocol can be adapted to any cell type for which suitable surface markers are present and which can be isolated from a subject. It is worth noting that the method described in this paper can also be applied to humans, rats, and monkeys by optimizing the protocol. In this example, the exogenous agent is a fluorescent protein and expression i...

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Abstract

The present disclosure provides, at least in part, methods and compositions for in vivo fusosome delivery. In some embodiments, the fusosome comprises a combination of elements that promote specificity for target cells, e.g., one or more of a re-targeted fusogen, a positive target cell-specific regulatory element, and a non-target cell-specific regulatory element. In some embodiments, the fusosomecomprises one or more modifications that decrease an immune response against the fusosome.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Serial No. 62 / 671,838, filed May 15, 2018, and U.S. Serial No. 62 / 695,529, filed July 9, 2018, each of which is incorporated herein by reference in its entirety. [0003] Merge Sequence Listings by Reference [0004] This application is being filed with a sequence listing in electronic format. The Sequence Listing is provided as a file named V2050-7023WO Sequence Listing.TXT, which was created on May 14, 2019, and is 651 kilobytes in size. The information of the sequence listing in electronic format is incorporated herein by reference in its entirety. Background technique [0005] Combination biologics are promising therapeutic candidates for a variety of diseases. However, delivery of large biologics into cells is difficult because the plasma membrane acts as a barrier between the cell and the extracellular space. There is a need in the art for new methods of delivering co...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/54A61P35/00C12N5/10C12N15/867
CPCA61K35/28C12N2740/10043C12N15/87A61K35/15C07K14/005A61K9/1271C12N2509/00A61K48/005C12N2760/18034A61K48/0008A61K9/127C12N15/88C12N2830/007
Inventor G.A.冯马尔特扎恩J.R.鲁宾斯M.T.米J.M.米尔维德N.F.戈登J.V.沙K.M.特鲁杜B.J.哈特利P.A.约翰斯
Owner FLAGSHIP PIONEERING INNOVATIONS V INC
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