ADENO-ASSOCIATED VARIANTS, FORMULATIONS AND METHODS FOR PULMONARY DELIVERY

To provide Adeno-associated variants, formulations and methods for pulmonary delivery.SOLUTION: The disclosure provides a variant AAV capsid protein that confers tropism to lung cells, a recombinant adeno-associated virus including the variant AAV and a pharmaceutical composition comprising the same...

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Hauptverfasser:	MELISSA KOTTERMAN, CHRISTOPHER SCHMITT, MELISSA CALTON, PETER FRANCIS, ROXANNE CROZE, JOHNNY GONZALES
Format:	Patent
Sprache:	eng ; jpn
Schlagworte:	BEER BIOCHEMISTRY CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA ENZYMOLOGY HUMAN NECESSITIES HYGIENE MEDICAL OR VETERINARY SCIENCE METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS SPIRITS VINEGAR WINE
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Beschreibung
Zusammenfassung:	To provide Adeno-associated variants, formulations and methods for pulmonary delivery.SOLUTION: The disclosure provides a variant AAV capsid protein that confers tropism to lung cells, a recombinant adeno-associated virus including the variant AAV and a pharmaceutical composition comprising the same, and their use in the delivery of heterologous nucleic acids to lung cells for treating pulmonary disorders. In some embodiments, provided is a recombinant adeno-associated virus (rAAV) vector comprising (i) a capsid comprising a capsid protein of a specific sequence and (ii) a nucleic acid comprising from 5' to 3': (a) an AAV2 terminal repeat; (b) a promoter; (c) a nucleotide sequence encoding a human cystic fibrosis transmembrane conductance regulator (CFTR) protein or a biologically active truncated CFTR protein lacking amino acids 708-759 of the human CFTR protein sequence; (d) a polyadenylation sequence; and (e) an AAV2 terminal repeat.SELECTED DRAWING: None 【課題】肺送達のためのアデノ随伴バリアント、製剤および方法の提供。【解決手段】本開示は、肺細胞に対するトロピズムを付与するバリアントＡＡＶカプシドタンパク質、ならびにバリアントＡＡＶを含む組換えアデノ随伴ウイルスおよびそれを含む医薬組成物、および肺障害の処置のための、異種核酸の肺細胞への送達におけるそれらの使用を提供する。一部の実施形態では、（ｉ）特定配列のカプシドタンパク質を含むカプシドと、（ｉｉ）５'から３'に、（ａ）ＡＡＶ２末端反復、（ｂ）プロモーター、（ｃ）ヒト嚢胞性線維症膜コンダクタンス調節因子（ＣＦＴＲ）タンパク質またはヒトＣＦＴＲタンパク質配列のアミノ酸７０８～７５９を欠く生物活性のある短縮型ＣＦＴＲタンパク質をコードするヌクレオチド配列、（ｄ）ポリアデニル化配列および（ｅ）ＡＡＶ２末端反復を含む核酸とを含む組換えアデノ随伴ウイルス（ｒＡＡＶ）ベクターが本明細書で提供される。【選択図】なし