JPWO2019195714A5 - - Google Patents
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- JPWO2019195714A5 JPWO2019195714A5 JP2020554510A JP2020554510A JPWO2019195714A5 JP WO2019195714 A5 JPWO2019195714 A5 JP WO2019195714A5 JP 2020554510 A JP2020554510 A JP 2020554510A JP 2020554510 A JP2020554510 A JP 2020554510A JP WO2019195714 A5 JPWO2019195714 A5 JP WO2019195714A5
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- coding sequence
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Description
参考文献
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66. Kamata Y, Taniguchi A, Yamamoto M, et al. Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids. The Journal of biological chemistry. 2009;284(19):12829-12836.
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本開示は以下の実施形態を包含する。
[１] ポリペプチドを分泌することができる組換え微生物であって、該ポリペプチドを発現することができる遺伝子を含む第1のコード配列と、細胞透過性ペプチドを発現することができる遺伝子を含む第2のコード配列とを含む発現ベクターを含む、組換え微生物。
[２] 移行シグナルを発現することができる遺伝子を含む第3のコード配列をさらに含む、実施形態１に記載の組換え微生物。
[３] 第1のコード配列、第2のコード配列および第3のコード配列の発現が、プロモーターの制御下にある、実施形態１または２に記載の組換え微生物。
[４] 第1のコード配列、第2のコード配列および第3のコード配列の配置が、インフレームである、実施形態３に記載の組換え微生物。
[５] 第1のコード配列、第2のコード配列および第3のコード配列が、プロモーターに機能し得る形で連結されている、実施形態２に記載の組換え微生物。
[６] 組換え微生物が、細菌、または細菌の組合せである、実施形態２に記載の組換え微生物。
[７] ポリペプチドが、フィラグリン、またはそのバリアントである、実施形態１に記載の組換え微生物。
[８] 微生物が、ビフィドバクテリウム(Bifidobacterium)、ブレヴィバクテリウム(Brevibacterium)、プロピオニバクテリウム(Propionibacterium)、ラクトコッカス(Lactococcus)、ストレプトコッカス(Streptococcus)、スタフィロコッカス(Staphylococcus)、ラクトバチルス(Lactobacillus)、エンテロコッカス(Enterococcus)、ペディオコッカス(Pediococcus)、ロイコノストック(Leuconostoc)、もしくはオエノコッカス(Oenococcus)、またはその組合せからなる群から選択される、実施形態１に記載の組換え微生物。
[９] 組換え微生物が、表皮ブドウ球菌(Staphylococcus epidermidis)である、実施形態１に記載の組換え微生物。
[１０] 微生物が、フィラグリン融合タンパク質を分泌する、実施形態１に記載の組換え微生物。
[１１] フィラグリン融合タンパク質が配列番号１と９５％配列同一であるアミノ酸配列を有する、実施形態１０に記載の組換え微生物。
[１２] 生きた生物治療組成物を製造するための方法であって、
(a)細胞に、(i)治療ポリペプチドを発現することができる核酸配列を含む第1のコード配列、および(ii)細胞透過性ペプチドを発現することができる核酸配列を含む第2のコード配列をトランスフェクトすることと、
(b)トランスフェクトされた細胞に、治療ポリペプチド融合タンパク質を産生させることと、
(c)生きた生物治療組成物を取得することと、
を含む、方法。
[１３] (iii)細胞に、移行シグナルを発現することができる核酸配列を含む第3のコード配列をトランスフェクトすることをさらに含む、実施形態１２に記載の方法。
[１４] 第1のコード配列、第2のコード配列および第3のコード配列が、単一のプラスミド中に配置される、実施形態１２に記載の方法。
[１５] 第1のコード配列、第2のコード配列および第3のコード配列の配置が、プロモーターに機能し得る形で連結される、実施形態１３に記載の方法。
[１６] 細胞が、ビフィドバクテリウム(Bifidobacterium)、ブレヴィバクテリウム(Brevibacterium)、プロピオニバクテリウム(Propionibacterium)、ラクトコッカス(Lactococcus)、ストレプトコッカス(Streptococcus)、スタフィロコッカス(Staphylococcus)、ラクトバチルス(Lactobacillus)、エンテロコッカス(Enterococcus)、ペディオコッカス(Pediococcus)、ロイコノストック(Leuconostoc)、もしくはオエノコッカス(Oenococcus)、またはその組合せからなる群から選択される微生物からなる群から選択される、実施形態１２に記載の方法。
[１７] 細胞が、表皮ブドウ球菌(Staphylococcus epidermidis)である、実施形態１２に記載の方法。
[１８] 治療ポリペプチド融合タンパク質が、フィラグリン融合タンパク質、またはそのバリアントである、実施形態１２に記載の方法。
[１９] フィラグリン融合タンパク質が配列番号１と９５％配列同一であるアミノ酸配列を有する、実施形態１１に記載の方法。
[２０] 実施形態１２～１９のいずれかに記載の方法によって得られた組成物。
[２１] 水性溶液、エマルジョン、クリーム、ローション、ゲル、または軟膏からなる群から選択される製薬上許容し得る担体を含む、実施形態２０に記載の組成物。
[２２] 組換え微生物を含む生きた生物治療組成物であって、組換え微生物が、
(i)治療ポリペプチドを発現することができる核酸配列を含む第1のコード配列；
(ii)細胞透過性ペプチドを発現することができる核酸配列を含む第2のコード配列；
(iii)移行シグナルを発現することができる核酸配列を含む第3のコード配列；ならびに (iv)第1のコード配列、第2のコード配列および第3のコード配列に機能し得る形で連結されているプロモーター
を含み、
第1のコード配列、第2のコード配列および第1のコード配列が、フィラグリン融合産物、またはそのバリアントを発現することができる、生きた生物治療組成物。
[２３] 組換え微生物が、表皮ブドウ球菌(Staphylococcus epidermidis)である、実施形態２２に記載の組成物。
[２４] 移行シグナルが、フィラグリン融合産物、またはそのバリアントを、組換え微生物から外部へ輸送する、実施形態２２または２３に記載の組成物。
[２５] フィラグリン融合タンパク質が配列番号１と９５％配列同一であるアミノ酸配列を有する、実施形態２４に記載の組成物。
[２６] 細胞透過性ペプチドが、フィラグリン融合産物、またはそのバリアントの、ヒトケラチノサイトへの進入を容易にする、実施形態２０に記載の組成物。
[２７] 水性溶液、エマルジョン、クリーム、ローション、ゲル、または軟膏からなる群から選択される製薬上許容し得る担体を含む、実施形態２２に記載の組成物。
[２８] 実施形態２２～２７のいずれかに記載の組成物、および、使用のための指示書を含む、キット。
[２９] 皮膚疾患の処置を必要とする対象に、実施形態１～１０または１８～２３のいずれかに記載の組成物を投与することを含む、皮膚疾患を処置する方法。
[３０] 皮膚疾患が尋常性魚鱗癬(IV)である、実施形態２９に記載の方法。
[３１] 皮膚疾患がアトピー性皮膚炎である、実施形態２９に記載の方法。
[３２] フィラグリンポリペプチド、またはそのバリアントを含む、組成物。
[３３] フィラグリンポリペプチドが融合タンパク質である、実施形態３２に記載の組成物。
[３４] フィラグリン融合タンパク質が配列番号１と９５％配列同一であるアミノ酸配列を有する、実施形態３３に記載の組成物。
[３５] フィラグリン融合タンパク質が配列番号１のアミノ酸配列からなる、実施形態３３に記載の組成物。
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The present disclosure includes the following embodiments.
[1] A recombinant microorganism capable of secreting a polypeptide, which comprises a first coding sequence containing a gene capable of expressing the polypeptide and a gene capable of expressing a cell-permeable peptide. A recombinant microorganism comprising an expression vector comprising a second coding sequence.
[2] The recombinant microorganism according to embodiment 1, further comprising a third coding sequence comprising a gene capable of expressing a translocation signal.
[3] The recombinant microorganism according to embodiment 1 or 2, wherein the expression of the first coding sequence, the second coding sequence and the third coding sequence is under the control of a promoter.
[4] The recombinant microorganism according to embodiment 3, wherein the arrangement of the first coding sequence, the second coding sequence and the third coding sequence is in-frame.
[5] The recombinant microorganism according to embodiment 2, wherein the first coding sequence, the second coding sequence, and the third coding sequence are linked in a manner capable of functioning as a promoter.
[6] The recombinant microorganism according to Embodiment 2, wherein the recombinant microorganism is a bacterium or a combination of bacteria.
[7] The recombinant microorganism according to embodiment 1, wherein the polypeptide is filaggrin or a variant thereof.
[8] Microbes are Bifidobacterium, Brevibacterium, Propionibacterium, Lactococcus, Streptococcus, Staphylococcus, Lactobacillus. The recombinant microorganism according to embodiment 1, selected from the group consisting of (Lactobacillus), Enterococcus, Pediococcus, Leuconostoc, or Oenococcus, or a combination thereof.
[9] The recombinant microorganism according to Embodiment 1, wherein the recombinant microorganism is Staphylococcus epidermidis.
[10] The recombinant microorganism according to embodiment 1, wherein the microorganism secretes a filaggrin fusion protein.
[11] The recombinant microorganism according to embodiment 10, wherein the filaggrin fusion protein has an amino acid sequence that is 95% identical in sequence to SEQ ID NO: 1.
[12] A method for producing a living biotherapeutic composition.
A first coding sequence containing (i) a nucleic acid sequence capable of expressing a therapeutic polypeptide in a cell, and (ii) a second coding sequence containing a nucleic acid sequence capable of expressing a cell-permeable peptide. Transfecting the sequence and
(b) To cause the transfected cells to produce a therapeutic polypeptide fusion protein.
(c) Obtaining a living biotherapeutic composition and
Including, how.
[13] (iii) The method of embodiment 12, further comprising transfecting cells with a third coding sequence comprising a nucleic acid sequence capable of expressing a translocation signal.
[14] The method of embodiment 12, wherein the first coding sequence, the second coding sequence and the third coding sequence are located in a single plasmid.
[15] The method of embodiment 13, wherein the first coding sequence, the second coding sequence and the arrangement of the third coding sequence are ligated in a manner capable of functioning as a promoter.
[16] The cells are Bifidobacterium, Brevibacterium, Propionibacterium, Lactococcus, Streptococcus, Staphylococcus, Lactobacillus. Embodiment selected from the group consisting of microorganisms selected from the group consisting of (Lactobacillus), Enterococcus, Pediococcus, Leuconostoc, or Oenococcus, or a combination thereof. 12. The method according to 12.
[17] The method of embodiment 12, wherein the cells are Staphylococcus epidermidis.
[18] The method of embodiment 12, wherein the therapeutic polypeptide fusion protein is a filaggrin fusion protein, or a variant thereof.
[19] The method of embodiment 11, wherein the filaggrin fusion protein has an amino acid sequence that is 95% identical in sequence to SEQ ID NO: 1.
[20] The composition obtained by the method according to any one of embodiments 12 to 19.
[21] The composition according to embodiment 20, comprising a pharmaceutically acceptable carrier selected from the group consisting of aqueous solutions, emulsions, creams, lotions, gels, or ointments.
[22] A living biotherapeutic composition comprising a recombinant microorganism, wherein the recombinant microorganism is:
(i) A first coding sequence containing a nucleic acid sequence capable of expressing a therapeutic polypeptide;
(ii) A second coding sequence containing a nucleic acid sequence capable of expressing a cell-permeable peptide;
(iii) A third coding sequence containing a nucleic acid sequence capable of expressing a translocation signal; and (iv) linked to a first coding sequence, a second coding sequence and a third coding sequence in a functional manner. Promoter
Including
A living biotherapeutic composition in which the first coding sequence, the second coding sequence and the first coding sequence can express a filaggrin fusion product or a variant thereof.
[23] The composition according to embodiment 22, wherein the recombinant microorganism is Staphylococcus epidermidis.
[24] The composition according to embodiment 22 or 23, wherein the migration signal transports the filaggrin fusion product, or a variant thereof, out of the recombinant microorganism.
[25] The composition of embodiment 24, wherein the filaggrin fusion protein has an amino acid sequence that is 95% identical in sequence to SEQ ID NO: 1.
[26] The composition according to embodiment 20, wherein the cell-permeable peptide facilitates entry of the filaggrin fusion product, or variant thereof, into human keratinocytes.
[27] The composition according to embodiment 22, comprising a pharmaceutically acceptable carrier selected from the group consisting of aqueous solutions, emulsions, creams, lotions, gels, or ointments.
[28] A kit comprising the composition according to any of embodiments 22-27 and instructions for use.
[29] A method for treating a skin disease, which comprises administering the composition according to any one of embodiments 1 to 10 or 18 to 23 to a subject in need of treatment for the skin disease.
[30] The method of embodiment 29, wherein the skin disease is ichthyosis vulgaris (IV).
[31] The method according to embodiment 29, wherein the skin disease is atopic dermatitis.
[32] A composition comprising a filaggrin polypeptide, or a variant thereof.
[33] The composition according to embodiment 32, wherein the filaggrin polypeptide is a fusion protein.
[34] The composition of embodiment 33, wherein the filaggrin fusion protein has an amino acid sequence that is 95% identical in sequence to SEQ ID NO: 1.
[35] The composition according to embodiment 33, wherein the filaggrin fusion protein comprises the amino acid sequence of SEQ ID NO: 1.
Claims (33)
(a)細胞に、(i)治療ポリペプチドを発現することができる核酸配列を含む第1のコード配列、および(ii)細胞透過性ペプチドを発現することができる核酸配列を含む第2のコード配列をトランスフェクトすることと、
(b)トランスフェクトされた細胞に、治療ポリペプチド融合タンパク質を産生させることと、
(c)生きた生物治療組成物を取得することと、
を含む、方法。 A method for producing a living biotherapeutic composition,
A first coding sequence containing (i) a nucleic acid sequence capable of expressing a therapeutic polypeptide in a cell, and (ii) a second coding sequence containing a nucleic acid sequence capable of expressing a cell-permeable peptide. Transfecting the sequence and
(b) To cause the transfected cells to produce a therapeutic polypeptide fusion protein.
(c) Obtaining a living biotherapeutic composition and
Including, how.
(i)治療ポリペプチドを発現することができる核酸配列を含む第1のコード配列；
(ii)細胞透過性ペプチドを発現することができる核酸配列を含む第2のコード配列；
(iii)移行シグナルを発現することができる核酸配列を含む第3のコード配列；ならびに (iv)第1のコード配列、第2のコード配列および第3のコード配列に機能し得る形で連結されているプロモーター
を含み、
第1のコード配列、第2のコード配列および第1のコード配列が、フィラグリン融合産物、またはそのバリアントを発現することができる、生きた生物治療組成物。 A living biotherapeutic composition comprising a recombinant microorganism, wherein the recombinant microorganism is:
(i) A first coding sequence containing a nucleic acid sequence capable of expressing a therapeutic polypeptide;
(ii) A second coding sequence containing a nucleic acid sequence capable of expressing a cell-permeable peptide;
(iii) A third coding sequence containing a nucleic acid sequence capable of expressing a translocation signal; and (iv) linked to a first coding sequence, a second coding sequence and a third coding sequence in a functional manner. Including promoters
A living biotherapeutic composition in which the first coding sequence, the second coding sequence and the first coding sequence can express a filaggrin fusion product or a variant thereof.
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| GB0525492D0 (en) | 2005-12-15 | 2006-01-25 | Univ Dundee | Filaggrin |
| AU2010321784B2 (en) * | 2009-11-23 | 2014-04-24 | Research Development Foundation | Recombinant filaggrin polypeptides for cell importation |
| AU2014203006B2 (en) | 2009-11-23 | 2016-05-19 | Research Development Foundation | Recombinant filaggrin polypeptides for cell importation |
| US9283287B2 (en) * | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| EP2909321A4 (en) * | 2012-10-16 | 2016-06-22 | Massachusetts Inst Technology | Production of stable non-polyadenylated rnas |
| EP4249036A3 (en) * | 2014-01-31 | 2023-10-25 | Factor Bioscience Inc. | Methods and products for nucleic acid production and delivery |
| US10702558B2 (en) * | 2014-05-30 | 2020-07-07 | Azitra Inc | Therapeutic treatment of skin disease with recombinant commensal skin microorganisms |
| KR20200051001A (en) * | 2017-09-05 | 2020-05-12 | 아지트라 인코포레이티드 | Methods and compositions for treating inflammatory skin diseases using recombinant microorganisms |
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