# US 2026/0076907 A1 · Compositions and methods for compartment-specific cargo delivery

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- Number: US 2026/0076907 A1
- Document ID: US20260076907A1
- Status: Published application
- Kind: A1
- Application number: 19/388,343
- Filed: 2025-11-13
- Published: 2026-03-19
- Earliest claimed: 2018-11-14
- Assignees: Flagship Pioneering Innovations V, Inc.
- Applicants: Flagship Pioneering Innovations V, Inc.
- Inventors: Geoffrey A. von Maltzahn; John Miles Milwid; Jacob Rosenblum Rubens; Michael Travis Mee; Neal Francis Gordon; Jagesh Vijaykumar Shah; Kyle Marvin Trudeau; Brigham Jay Hartley
- Web page: https://patentgrep.com/patent/US20260076907A1

## CPC

- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543})
- A61K 9/5176: {Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/5123)}
- A61K 38/164: {from bacteria}
- A61K 38/45: Transferases (2)
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C07K 2319/09: containing a nuclear localisation signal
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Fusosome compositions and methods are described herein.

## Claims

### Claim 1

A fusosome comprising:
(a) a lipid bilayer comprising a plurality of lipids obtained from a source cell;
(b) a lumen surrounded by the lipid bilayer;
(c) a fusogen that is exogenous or overexpressed relative to the source cell, wherein the fusogen is disposed in the lipid bilayer, and wherein the fusogen comprises a paramyxoviral fusogen; and
(d) a nuclear payload agent for delivery to the nucleus of a target cell, wherein the nuclear payload agent comprises a nucleic acid sequence encoding an antibody molecule.

### Claim 2 (depends on 1)

The fusosome of claim 1, wherein the antibody molecule comprises a Fab, an scFv, an scFab, a sdAb, a duobody, a minibody, a nanobody, a diabody, a zybody, a camelid antibody, a BiTE, a quadroma, or a bsDb.

### Claim 3 (depends on 1)

The fusosome of claim 1, wherein the source cell is a primary cell, a cultured cell, an immortalized cell, or a cell line.

### Claim 4 (depends on 1)

The fusosome of claim 1, wherein the source cell is allogeneic.

### Claim 5 (depends on 1)

The fusosome of claim 1, wherein the source cell is autologous.

### Claim 6 (depends on 1)

The fusosome of claim 1, wherein the fusosome is from a source cell having a modified genome that exhibits reduced immunogenicity.

### Claim 7 (depends on 1)

The fusosome of claim 1, wherein the fusosome:
(i) has a diameter that is less than about 0.01% or 1% of that of the source cell; or
(ii) is active at a pH of 6-8.

### Claim 8 (depends on 1)

The fusosome of claim 1, wherein the fusosome comprises a targeting domain which localizes the fusosome to a target cell.

### Claim 9 (depends on 8)

The fusosome of claim 8, wherein the targeting domain interacts with a target cell moiety on the target cell.

### Claim 10 (depends on 8)

The fusosome of claim 8, wherein the fusogen comprises the targeting domain.

### Claim 11 (depends on 1)

The fusosome of claim 1, wherein the target cell is in an organism or is a primary cell isolated from an organism.

### Claim 12 (depends on 1)

The fusosome of claim 1, wherein the target cell is selected from an endothelial cell, a fibroblast, a blood cell, a stem cell, an embryonic stem cell, a myoblast, a parenchymal cell, an alveolar cell, a neuron, a precursor cell, a progenitor cell, or an immortalized cell.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising the fusosome of claim 1.

### Claim 14 (depends on 1)

The fusosome of claim 1, wherein when contacted with a target cell population, the fusosome delivers the payload agent via a non-endocytic pathway.

### Claim 15 (depends on 14)

The fusosome of claim 14, wherein the level of payload delivered via a non-endocytic pathway for a given fusosome composition is 0.1-0.95 of the level of payload delivered to a chloroquine treated reference cell.

### Claim 16 (depends on 1)

The fusosome of claim 1, wherein the paramyxovirus fusogen comprises a Nipah virus protein F, a measles virus F protein, a tupaia paramyxovirus F protein, a paramyxovirus F protein, a Hendra virus F protein, a Henipavirus F protein, a Morbillivirus F protein, a respirovirus F protein, a Sendai virus F protein, a rubulavirus F protein, or an avulavirus F protein.

### Claim 17 (depends on 1)

A method of manufacturing a fusosome composition, comprising:
i) providing a plurality of fusosomes according to claim 1; and
ii) formulating the plurality of fusosomes as a pharmaceutical composition suitable for administration to a subject.

### Claim 18 (depends on 1)

A method of administering a fusosome composition to a subject, comprising administering to the subject a fusosome composition comprising a plurality of fusosomes according to claim 1, thereby administering the fusosome composition to the subject.

### Claim 19 (depends on 1)

A method of delivering a payload agent to a subject, comprising administering to the subject a fusosome composition comprising a plurality of fusosomes according to claim 1, wherein the fusosome composition is administered in an amount and/or time such that the payload agent is delivered.

### Claim 20 (depends on 1)

A method of treating a disease or disorder in a subject comprising administering to the subject a plurality of fusosomes according to claim 1, wherein the plurality of fusosomes is administered in an amount and/or time such that the disease or disorder is treated.