ENGINEERED COMMENSAL BACTERIA AND METHODS OF USE

• Main Authors: JULIET SNYDER, AMIR ZARRINPAR, STEVEN BROWN
• Format: Patent
• Language: English; Japanese
• Published: 29.06.2023
• Subjects: AGRICULTURE; ANIMAL HUSBANDRY; BEER; BIOCHEMISTRY; CARE OF BIRDS, FISHES, INSECTS; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; FISHING; FOODS OR FOODSTUFFS; FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BYSUBCLASSES A23B - A23J; FORESTRY; HUMAN NECESSITIES; HUNTING; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; NEW BREEDS OF ANIMALS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OFNUTRITIVE QUALITIES, PHYSICAL TREATMENT; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES; TRAPPING; VINEGAR; WINE

To provide compositions comprising populations of commensal bacteria isolated from a microbiome sample of a mammalian subject and engineered to express a heterologous polynucleotide, compositions comprising such engineered commensal bacteria and methods of use for delivering a therapeutic polypeptide to a mammal, e.g, by administering the engineered commensal/native bacteria.SOLUTION: Disclosed is a method of delivering a therapeutic polypeptide to a mammalian subject in need thereof, the method comprising: a) obtaining a microbiome sample comprising bacterial cells from a donating subject; b) isolating a bacterial cell from the microbiome sample, where the bacteria cell is from a bacterial strain that is commensal/native to the donating subject; c) culturing the isolated bacterial cell in vitro to yield a substantially homogeneous population of the isolated and cultured bacteria cell; d) transforming the bacterial cell population with one or more polynucleotides that are heterologous to the bacteria and/or the donating subject, where the one or more polynucleotides encode one or more therapeutic polypeptides; and e) administering or causing to be administered to a receiving subject at least a portion of the substantially homogeneous and transformed population of the isolated and cultured bacterial cells, where the administered bacterial cells are capable of colonizing permanently or long-term in or on the mammalian subject and expressing the one or more therapeutic polypeptides.SELECTED DRAWING: None 【課題】哺乳類対象のマイクロバイオームサンプルから単離した、異種ポリヌクレオチドを発現するように操作された共生細菌の集団を含む組成物、このような操作された共生細菌を含む組成物、及び例えば操作された共生/天然細菌を投与することによって哺乳動物に治療用ポリペプチドを送達するための使用方法が提供される。【解決手段】治療用ポリペプチドをそれを必要とする哺乳類対象に送達する方法であって、a)供与対象から、細菌細胞を含むマイクロバイオームサンプルを得る工程;b)マイクロバイオームサンプルから細菌細胞を単離する工程であり、細菌細胞は、供与対象にとって共生的な/天然の菌株に由来する、工程;c)単離された細菌細胞をインビトロで培養して、単離及び培養された細菌細胞の実質的に均一な集団を得る工程;d)細菌細胞の集団を、細菌及び/又は供与対象にとって異種である1つ又は複数のポリヌクレオチドで形質転換する工程であり、1つ又は複数のポリヌクレオチドは、1つ又は複数の治療用ポリペプチドをコードする、工程;及びe)受容対象に単離及び培養された細菌細胞の実質的に均一な形質転換された集団の少なくとも一部を投与する、又はその投与を引き起こす工程であり、投与される細菌細胞は、哺乳類対象中又はその上に永久的に又は長期にわたり定着することが可能であり、1つ又は複数の治療用ポリペプチドを発現する、工程を含む、方法。【選択図】なし