JPWO2021195218A5 - - Google Patents
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- JPWO2021195218A5 JPWO2021195218A5 JP2022557747A JP2022557747A JPWO2021195218A5 JP WO2021195218 A5 JPWO2021195218 A5 JP WO2021195218A5 JP 2022557747 A JP2022557747 A JP 2022557747A JP 2022557747 A JP2022557747 A JP 2022557747A JP WO2021195218 A5 JPWO2021195218 A5 JP WO2021195218A5
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Description
参考文献
特許及び特許出願を含むがこれらに限定されない、本明細書及び本明細書の実施例で引用される全ての刊行物及び参考文献は、あたかも個々の刊行物又は参考文献が、完全に記載されるように参照により本明細書に組み込まれることが具体的かつ個別に示されるかのように、それらの全体が参照により組み込まれる。この出願が優先権を主張する任意の特許出願もまた、刊行物及び参考文献について上述した方法で、参照により本明細書に組み込まれる。
本発明は、例えば、以下の項目を提供する。
（項目１）
カプシド不含閉端ＤＮＡ（ｃｅＤＮＡ）ベクターであって、
隣接する逆方向末端反復配列（ＩＴＲ）間に少なくとも１つの核酸配列を含み、少なくとも１つの核酸配列が、少なくとも１つのベータグルコセレブロシダーゼ（ＧＢＡ）タンパク質をコードする、ｃｅＤＮＡベクター。
（項目２）
前記少なくとも１つのＧＢＡタンパク質をコードする少なくとも１つの核酸配列が、表１に示される配列のうちのいずれか、又は表１３のオープンリーディングフレーム配列（ＯＲＦ）のうちのいずれかから選択される、項目１に記載のｃｅＤＮＡベクター。
（項目３）
前記ｃｅＤＮＡベクターが、前記少なくとも１つのＧＢＡタンパク質をコードする少なくとも１つの核酸配列に作動可能に連結された、表７のプロモーターのうちのいずれかから選択されるプロモーターを含む、項目１又は２に記載のｃｅＤＮＡベクター。
（項目４）
前記ｃｅＤＮＡベクターが、表８のエンハンサーのうちのいずれかから選択されるエンハンサーを含む、項目１～３のいずれか一項に記載のｃｅＤＮＡベクター。
（項目５）
前記ｃｅＤＮＡベクターが、表９Ａの５’ＵＴＲ及び／又はイントロン配列のうちのいずれかから選択される５’ＵＴＲ及び／又はイントロン配列を含む、項目１～４のいずれか一項に記載のｃｅＤＮＡベクター。
（項目６）
前記ｃｅＤＮＡベクターが、表９Ｂの３’ＵＴＲ配列のうちのいずれかから選択される３’ＵＴＲ配列を含む、項目１～５のいずれか一項に記載のｃｅＤＮＡベクター。
（項目７）
前記ｃｅＤＮＡベクターが、表１０のポリＡ配列のうちのいずれかから選択される少なくとも１つのポリＡ配列を含む、項目１～６のいずれか一項に記載のｃｅＤＮＡベクター。
（項目８）
前記ｃｅＤＮＡベクターが、少なくとも１つの核酸配列に作動可能に連結された少なくとも１つのプロモーター配列を含む、項目１～７のいずれか一項に記載のｃｅＤＮＡベクター。
（項目９）
少なくとも１つの核酸配列が、ｃＤＮＡである、項目１～８のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１０）
少なくとも１つのＩＴＲが、機能的末端分解部位及びＲｅｐ結合部位を含む、項目１～９のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１１）
前記ＩＴＲの一方又は両方が、パルボウイルス、ディペンドウイルス、及びアデノ随伴ウイルス（ＡＡＶ）から選択されるウイルスに由来する、項目１～１０のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１２）
前記隣接するＩＴＲが、互いに対して対称又は非対称である、項目１～１１のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１３）
前記隣接するＩＴＲが、対称又は実質的に対称である、項目１２に記載のｃｅＤＮＡベクター。
（項目１４）
前記隣接するＩＴＲが、非対称である、項目１２に記載のｃｅＤＮＡベクター。
（項目１５）
前記ＩＴＲの一方若しくは両方が野生型であるか、又は前記ＩＴＲの両方が野生型ＩＴＲである、項目１～１４のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１６）
前記隣接するＩＴＲが、異なるウイルス血清型に由来する、項目１～１５のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１７）
前記隣接するＩＴＲが、表２に示されるウイルス血清型のいずれかの対から選択される、項目１～１６のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１８）
前記ＩＴＲの一方又は両方が、表３に示される配列から選択される配列を含む、項目１～１７のいずれか一項に記載のｃｅＤＮＡベクター。
（項目１９）
前記ＩＴＲの少なくとも一方が、野生型ＡＡＶ ＩＴＲ配列から、前記ＩＴＲの全体的な三次元立体構造に影響を与える欠失、付加、又は置換によって変更されている、項目１～１８のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２０）
前記ＩＴＲの一方又は両方が、ＡＡＶ１、ＡＡＶ２、ＡＡＶ３、ＡＡＶ４、ＡＡＶ５、ＡＡＶ６、ＡＡＶ７、ＡＡＶ８、ＡＡＶ９、ＡＡＶ１０、ＡＡＶ１１、及びＡＡＶ１２から選択されるＡＡＶ血清型に由来する、項目１～１９のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２１）
前記ＩＴＲの一方又は両方が、合成のものである、項目１～２０のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２２）
前記ＩＴＲの一方若しくは両方が野生型ＩＴＲでないか、又は前記ＩＴＲの両方が野生型ＩＴＲでない、項目１～２１のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２３）
前記ＩＴＲの一方又は両方が、Ａ、Ａ’、Ｂ、Ｂ’、Ｃ、Ｃ’、Ｄ、及びＤ’から選択されるＩＴＲ領域のうちの少なくとも１つにおける欠失、挿入、及び／又は置換によって修飾されている、項目１～２２のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２４）
前記欠失、前記挿入、及び／又は前記置換が、通常は前記Ａ、Ａ’、Ｂ、Ｂ’、Ｃ、又はＣ’領域によって形成されるステムループ構造の全部又は一部の欠失をもたらす、項目２３に記載のｃｅＤＮＡベクター。
（項目２５）
前記ＩＴＲの一方又は両方が、通常は前記Ｂ及びＢ’領域によって形成されるステムループ構造の全部又は一部の欠失をもたらす、欠失、挿入、及び／又は置換によって修飾されている、項目１～２４のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２６）
前記ＩＴＲの一方又は両方が、通常は前記Ｃ及びＣ’領域によって形成されるステムループ構造の全部又は一部の欠失をもたらす、欠失、挿入、及び／又は置換によって修飾されている、項目１～２４のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２７）
前記ＩＴＲの一方又は両方が、通常は前記Ｂ及びＢ’領域によって形成されるステムループ構造の一部、並びに／又は通常は前記Ｃ及びＣ’領域によって形成されるステムループ構造の一部の欠失をもたらす、欠失、挿入、及び／又は置換によって修飾されている、項目１～２４のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２８）
前記ＩＴＲの一方又は両方が、通常は前記Ｂ及びＢ’領域によって形成される第１のス
テムループ構造と、前記Ｃ及びＣ’領域によって形成される第２のステムループ構造とを含む領域に、単一のステムループ構造を含む、項目１～２７のいずれか一項に記載のｃｅＤＮＡベクター。
（項目２９）
前記ＩＴＲの一方又は両方が、通常は前記Ｂ及びＢ’領域によって形成される第１のステムループ構造と、前記Ｃ及びＣ’領域によって形成される第２のステムループ構造とを含む領域に、単一のステム及び２つのループを含む、項目１～２８のいずれか一項に記載のｃｅＤＮＡベクター。
（項目３０）
前記ＩＴＲの一方又は両方が、通常は前記Ｂ及びＢ’領域によって形成される第１のステムループ構造と、前記Ｃ及びＣ’領域によって形成される第２のステムループ構造とを含む領域に、単一のステム及び単一のループを含む、項目１～２９のいずれか一項に記載のｃｅＤＮＡベクター。
（項目３１）
前記ＩＴＲの両方が、前記ＩＴＲが互いに対して反転されたときに全体的な三次元対称性をもたらすような様式で変更されている、項目１～３０のいずれか一項に記載のｃｅＤＮＡベクター。
（項目３２）
前記ＩＴＲの一方又は両方が、表３，５Ａ、５Ｂ及び６に示される配列の１つ以上から選択される配列を含む、項目１～３１のいずれか一項に記載のｃｅＤＮＡベクター。
（項目３３）
少なくとも１つの核酸配列が、少なくとも１つの調節スイッチの制御下にある、項目１～３２のいずれか一項に記載のｃｅＤＮＡベクター。
（項目３４）
少なくとも１つの調節スイッチが、バイナリ調節スイッチ、小分子調節スイッチ、パスコード調節スイッチ、核酸ベース調節スイッチ、転写後調節スイッチ、放射線制御又は超音波制御の調節スイッチ、低酸素媒介調節スイッチ、炎症反応調節スイッチ、剪断活性化調節スイッチ、及びキルスイッチから選択される、項目３３に記載のｃｅＤＮＡベクター。
（項目３５）
表１３から選択される核酸配列を含む、カプシド不含閉端ＤＮＡ（ｃｅＤＮＡ）ベクター。
（項目３６）
配列番号３８５、配列番号３８６、配列番号３８７、配列番号３８８、配列番号３８９又は配列番号３９０から選択される核酸と少なくとも８５％同一である核酸配列を含む、カプシド不含閉端ＤＮＡ（ｃｅＤＮＡ）ベクター。
（項目３７）
配列番号３８５、配列番号３８６、配列番号３８７、配列番号３８８、配列番号３８９又は配列番号３９０からなる群から選択される核酸配列からなる、カプシド不含閉端ＤＮＡ（ｃｅＤＮＡ）ベクター。
（項目３８）
細胞におけるベータグルコセレブロシダーゼ（ＧＢＡ）タンパク質を発現する方法であって、前記細胞を項目１～３４のいずれか一項に記載のｃｅＤＮＡベクターと接触させることを含む、方法。
（項目３９）
配列番号３８５、配列番号３８６、配列番号３８７、配列番号３８８、配列番号３８９又は配列番号３９０のうちのいずれか１つに示されるＯＲＦ核酸配列の翻訳によって産生されるＧＢＡタンパク質。
（項目４０）
前記細胞が、肝細胞又は筋細胞である、項目３８に記載の方法。
（項目４１）
前記細胞が、インビトロ又はインビボにある、項目３８又は４０に記載の方法。
（項目４２）
前記少なくとも１つの核酸配列が、真核細胞における発現のためにコドン最適化される、項目３８～４１のいずれか一項に記載の方法。
（項目４３）
前記少なくとも１つの核酸配列が、最適化されたコドンであり、表５のいずれかから選択される、項目３８～４１のいずれか一項に記載の方法。
（項目４４）
ゴーシェ病を有する対象を治療する方法であって、項目１～３４のいずれか一項に記載のｃｅＤＮＡベクター、又は項目３９に記載のＧＢＡタンパク質を前記対象に投与することを含み、少なくとも１つの核酸配列が、少なくとも１つのベータグルコセレブロシダーゼ（ＧＢＡ）タンパク質をコードする、方法。
（項目４５）
前記少なくとも１つのＧＢＡタンパク質をコードする少なくとも１つの核酸配列が、表１に示される配列又は表１３に含まれるＯＲＦのうちのいずれかから選択される、項目４１に記載の方法。
（項目４６）
前記ｃｅＤＮＡベクターが、静脈内注射により投与される、項目４４又は４５に記載の方法。
（項目４７）
前記ｃｅＤＮＡベクターが、肝細胞、若しくは筋細胞、又はそれらの両方において前記ＧＢＡタンパク質を発現する、項目４４～４６のいずれか一項に記載の方法。
（項目４８）
前記ｃｅＤＮＡベクターが、筋肉内注射、髄腔内注射、又は静脈内注射のうちのいずれか１つ以上によって投与される、項目４４～４７のいずれか一項に記載の方法。
（項目４９）
項目１～３７のいずれか一項に記載のｃｅＤＮＡベクターを含む、薬学的組成物。
（項目５０）
項目１～３７のいずれか一項に記載のｃｅＤＮＡベクターを含有する、細胞。
（項目５１）
前記細胞が、肝細胞、若しくは筋細胞、又はそれらの両方である、項目５０に記載の細胞。
（項目５２）
項目１～３７のいずれか一項に記載のｃｅＤＮＡベクター及び脂質を含む、組成物。
（項目５３）
前記脂質が、脂質ナノ粒子（ＬＮＰ）である、項目５２に記載の組成物。
（項目５４）
項目１～３７のいずれか一項に記載のｃｅＤＮＡベクター、又は項目５２若しくは５３に記載の組成物、又は項目５０に記載の細胞を含む、キット。
All publications and references cited in this specification and the examples herein, including but not limited to patents and patent applications, are incorporated by reference in their entirety as if each individual publication or reference was specifically and individually indicated to be incorporated by reference herein as if fully set forth. Any patent application to which this application claims priority is also incorporated by reference herein in the manner described above for publications and references.
The present invention provides, for example, the following items.
(Item 1)
A capsid-free closed-ended DNA (ceDNA) vector, comprising:
A ceDNA vector comprising at least one nucleic acid sequence between flanking inverted terminal repeats (ITRs), the at least one nucleic acid sequence encoding at least one beta-glucocerebrosidase (GBA) protein.
(Item 2)
2. The ceDNA vector of claim 1, wherein the at least one nucleic acid sequence encoding the at least one GBA protein is selected from any of the sequences shown in Table 1 or any of the open reading frame sequences (ORFs) of Table 13.
(Item 3)
3. The ceDNA vector of claim 1 or 2, wherein the ceDNA vector comprises a promoter selected from any of the promoters in Table 7, operably linked to at least one nucleic acid sequence encoding the at least one GBA protein.
(Item 4)
4. The ceDNA vector of any one of items 1 to 3, wherein the ceDNA vector comprises an enhancer selected from any of the enhancers in Table 8.
(Item 5)
5. The ceDNA vector of any one of items 1 to 4, wherein the ceDNA vector comprises a 5'UTR and/or intron sequence selected from any of the 5'UTR and/or intron sequences of Table 9A.
(Item 6)
6. The ceDNA vector of any one of items 1 to 5, wherein the ceDNA vector comprises a 3'UTR sequence selected from any of the 3'UTR sequences in Table 9B.
(Item 7)
7. The ceDNA vector of any one of items 1 to 6, wherein the ceDNA vector comprises at least one polyA sequence selected from any of the polyA sequences in Table 10.
(Item 8)
8. The ceDNA vector according to any one of items 1 to 7, wherein the ceDNA vector comprises at least one promoter sequence operably linked to at least one nucleic acid sequence.
(Item 9)
9. The ceDNA vector of any one of items 1 to 8, wherein at least one nucleic acid sequence is a cDNA.
(Item 10)
10. The ceDNA vector according to any one of items 1 to 9, wherein at least one ITR comprises a functional terminal resolution site and a Rep binding site.
(Item 11)
11. The ceDNA vector of any one of items 1 to 10, wherein one or both of the ITRs are derived from a virus selected from parvovirus, dependovirus, and adeno-associated virus (AAV).
(Item 12)
12. The ceDNA vector of any one of items 1 to 11, wherein the flanking ITRs are symmetric or asymmetric with respect to each other.
(Item 13)
13. The ceDNA vector of item 12, wherein the flanking ITRs are symmetric or substantially symmetric.
(Item 14)
13. The ceDNA vector of claim 12, wherein the flanking ITRs are asymmetric.
(Item 15)
15. The ceDNA vector according to any one of items 1 to 14, wherein one or both of the ITRs are wild-type or both of the ITRs are wild-type ITRs.
(Item 16)
16. The ceDNA vector of any one of items 1 to 15, wherein the flanking ITRs are derived from different viral serotypes.
(Item 17)
17. The ceDNA vector of any one of items 1 to 16, wherein the flanking ITRs are selected from any pair of viral serotypes shown in Table 2.
(Item 18)
18. The ceDNA vector of any one of items 1 to 17, wherein one or both of the ITRs comprises a sequence selected from the sequences shown in Table 3.
(Item 19)
19. The ceDNA vector of any one of items 1 to 18, wherein at least one of the ITRs is altered from a wild-type AAV ITR sequence by a deletion, addition, or substitution that affects the overall three-dimensional conformation of the ITR.
(Item 20)
20. The ceDNA vector of any one of items 1 to 19, wherein one or both of the ITRs are derived from an AAV serotype selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12.
(Item 21)
21. The ceDNA vector of any one of items 1 to 20, wherein one or both of the ITRs are synthetic.
(Item 22)
22. The ceDNA vector of any one of items 1 to 21, wherein one or both of the ITRs are not wild-type ITRs, or both of the ITRs are not wild-type ITRs.
(Item 23)
23. The ceDNA vector according to any one of the preceding claims, wherein one or both of the ITRs are modified by a deletion, insertion and/or substitution in at least one of the ITR regions selected from A, A', B, B', C, C', D and D'.
(Item 24)
24. The ceDNA vector of item 23, wherein the deletion, insertion and/or substitution results in the deletion of all or part of the stem-loop structure normally formed by the A, A', B, B', C or C' region.
(Item 25)
25. The ceDNA vector according to any one of items 1 to 24, wherein one or both of the ITRs are modified by deletion, insertion and/or substitution, resulting in the deletion of all or part of the stem-loop structure normally formed by the B and B' regions.
(Item 26)
25. The ceDNA vector according to any one of items 1 to 24, wherein one or both of the ITRs are modified by deletion, insertion and/or substitution, resulting in the deletion of all or part of the stem-loop structure normally formed by the C and C' regions.
(Item 27)
25. The ceDNA vector according to any one of items 1 to 24, wherein one or both of the ITRs are modified by a deletion, insertion and/or substitution resulting in the deletion of part of the stem-loop structure normally formed by the B and B' regions and/or of part of the stem-loop structure normally formed by the C and C' regions.
(Item 28)
One or both of the ITRs are typically the first sequence formed by the B and B' regions.
28. The ceDNA vector according to any one of items 1 to 27, comprising a single stem-loop structure in the region comprising the stem-loop structure and the second stem-loop structure formed by the C and C' regions.
(Item 29)
29. The ceDNA vector according to any one of items 1 to 28, wherein one or both of the ITRs comprise a single stem and two loops, usually in a region comprising a first stem-loop structure formed by the B and B' regions and a second stem-loop structure formed by the C and C' regions.
(Item 30)
30. The ceDNA vector according to any one of items 1 to 29, wherein one or both of the ITRs comprise a single stem and a single loop in a region that typically comprises a first stem-loop structure formed by the B and B' regions and a second stem-loop structure formed by the C and C' regions.
(Item 31)
31. The ceDNA vector of any one of items 1 to 30, wherein both of the ITRs are modified in such a manner as to result in overall three-dimensional symmetry when the ITRs are inverted relative to each other.
(Item 32)
32. The ceDNA vector of any one of items 1 to 31, wherein one or both of the ITRs comprises a sequence selected from one or more of the sequences shown in Tables 3, 5A, 5B and 6.
(Item 33)
33. The ceDNA vector of any one of items 1 to 32, wherein at least one nucleic acid sequence is under the control of at least one regulatory switch.
(Item 34)
34. The ceDNA vector of item 33, wherein the at least one regulatory switch is selected from a binary regulatory switch, a small molecule regulatory switch, a passcode regulatory switch, a nucleic acid-based regulatory switch, a post-transcriptional regulatory switch, a radiation-controlled or ultrasound-controlled regulatory switch, a hypoxia-mediated regulatory switch, an inflammatory response regulatory switch, a shear-activated regulatory switch, and a kill switch.
(Item 35)
A capsid-free closed-ended DNA (ceDNA) vector comprising a nucleic acid sequence selected from Table 13.
(Item 36)
A capsid-free closed-ended DNA (ceDNA) vector comprising a nucleic acid sequence that is at least 85% identical to a nucleic acid selected from SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ ID NO:388, SEQ ID NO:389, or SEQ ID NO:390.
(Item 37)
A capsid-free closed-ended DNA (ceDNA) vector consisting of a nucleic acid sequence selected from the group consisting of SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ ID NO:388, SEQ ID NO:389 or SEQ ID NO:390.
(Item 38)
35. A method for expressing beta-glucocerebrosidase (GBA) protein in a cell, comprising contacting said cell with a ceDNA vector according to any one of items 1 to 34.
(Item 39)
A GBA protein produced by translation of the ORF nucleic acid sequence shown in any one of SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ ID NO:388, SEQ ID NO:389 or SEQ ID NO:390.
(Item 40)
39. The method of claim 38, wherein the cell is a liver cell or a muscle cell.
(Item 41)
41. The method of claim 38 or 40, wherein the cell is in vitro or in vivo.
(Item 42)
42. The method of any one of items 38 to 41, wherein the at least one nucleic acid sequence is codon-optimized for expression in a eukaryotic cell.
(Item 43)
42. The method of any one of items 38 to 41, wherein the at least one nucleic acid sequence is codon optimized and selected from any of Table 5.
(Item 44)
40. A method of treating a subject having Gaucher disease, comprising administering to the subject a ceDNA vector according to any one of claims 1 to 34, or a GBA protein according to claim 39, wherein at least one nucleic acid sequence encodes at least one beta-glucocerebrosidase (GBA) protein.
(Item 45)
42. The method of claim 41, wherein the at least one nucleic acid sequence encoding the at least one GBA protein is selected from any of the sequences shown in Table 1 or the ORFs contained in Table 13.
(Item 46)
46. The method of claim 44 or 45, wherein the ceDNA vector is administered by intravenous injection.
(Item 47)
47. The method of any one of claims 44 to 46, wherein the ceDNA vector expresses the GBA protein in liver cells, or muscle cells, or both.
(Item 48)
48. The method of any one of items 44 to 47, wherein the ceDNA vector is administered by any one or more of intramuscular, intrathecal, or intravenous injection.
(Item 49)
A pharmaceutical composition comprising the ceDNA vector according to any one of items 1 to 37.
(Item 50)
A cell containing the ceDNA vector according to any one of items 1 to 37.
(Item 51)
51. The cell of item 50, wherein the cell is a liver cell, or a muscle cell, or both.
(Item 52)
38. A composition comprising the ceDNA vector according to any one of items 1 to 37 and a lipid.
(Item 53)
53. The composition of claim 52, wherein the lipid is a lipid nanoparticle (LNP).
(Item 54)
A kit comprising the ceDNA vector according to any one of items 1 to 37, or the composition according to item 52 or 53, or the cell according to item 50.
Claims (28)
隣接する逆方向末端反復配列（ＩＴＲ）間に位置する少なくとも１つの核酸配列を含み、前記少なくとも１つの核酸配列が、少なくとも１つのベータグルコセレブロシダーゼ（ＧＢＡ）タンパク質をコードする、ｃｅＤＮＡベクター。 A capsid-free closed-ended DNA (ceDNA) vector, comprising:
A ceDNA vector comprising at least one nucleic acid sequence located between adjacent inverted terminal repeats (ITRs), said at least one nucleic acid sequence encoding at least one beta-glucocerebrosidase (GBA) protein.
前記ｃｅＤＮＡベクターが、表８に示される配列のうちのいずれかからなる群から選択されるエンハンサーを含む；
前記ｃｅＤＮＡベクターが、表９Ａに示される配列のうちのいずれかからなる群から選択される５’ＵＴＲ及び／又はイントロン配列を含む；
前記ｃｅＤＮＡベクターが、表９Ｂに示される配列のうちのいずれかからなる群から選択される３’ＵＴＲ配列を含む；
前記ｃｅＤＮＡベクターが、表１０に示される配列のうちのいずれかからなる群から選択される少なくとも１つのポリＡ配列を含む；及び／又は
前記ｃｅＤＮＡベクターが、前記少なくとも１つの核酸配列に作動可能に連結された少なくとも１つのプロモーター配列を含む、
請求項１又は２に記載のｃｅＤＮＡベクター。 the ceDNA vector comprises a promoter selected from any of the sequences shown in Table 7 linked to the at least one nucleic acid sequence encoding the at least one GBA protein ;
The ceDNA vector comprises an enhancer selected from the group consisting of any of the sequences shown in Table 8;
the ceDNA vector comprises a 5'UTR and/or intron sequence selected from the group consisting of any of the sequences shown in Table 9A;
the ceDNA vector comprises a 3'UTR sequence selected from the group consisting of any of the sequences shown in Table 9B;
The ceDNA vector comprises at least one polyA sequence selected from the group consisting of any of the sequences shown in Table 10; and/or
the ceDNA vector comprises at least one promoter sequence operably linked to the at least one nucleic acid sequence ;
A ceDNA vector according to claim 1 or 2.
前記隣接するＩＴＲが、対称又は実質的に対称である；又は
前記隣接するＩＴＲが、非対称である、
請求項１～６のいずれか一項に記載のｃｅＤＮＡベクター。 the adjacent ITRs are symmetric or asymmetric with respect to each other ;
the adjacent ITRs are symmetric or substantially symmetric; or
the adjacent ITRs are asymmetric ;
A ceDNA vector according to any one of claims 1 to 6 .
前記隣接するＩＴＲの一方が野生型ＩＴＲではないか、又は前記隣接するＩＴＲの両方が野生型ＩＴＲではない；
前記隣接するＩＴＲが、異なるウイルス血清型に由来する；
前記隣接するＩＴＲの一方又は両方が、ＡＡＶ１、ＡＡＶ２、ＡＡＶ３、ＡＡＶ４、ＡＡＶ５、ＡＡＶ６、ＡＡＶ７、ＡＡＶ８、ＡＡＶ９、ＡＡＶ１０、ＡＡＶ１１、及びＡＡＶ１２から選択されるＡＡＶ血清型に由来する；
前記隣接するＩＴＲの一方又は両方が、表２に示されるウイルス血清型のいずれかの対からなる群から選択される；及び／又は
前記隣接するＩＴＲの一方又は両方が、表３に示される配列の１つ以上からなる群から選択される配列を含む、
請求項１～７のいずれか一項に記載のｃｅＤＮＡベクター。 one of the flanking ITRs is wild type or both of the ITRs are wild type ITRs ;
one of the flanking ITRs is not a wild-type ITR or both of the flanking ITRs are not wild-type ITRs;
the flanking ITRs are from different viral serotypes;
one or both of the flanking ITRs are derived from an AAV serotype selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12;
one or both of the flanking ITRs are selected from the group consisting of any pair of viral serotypes shown in Table 2; and/or
One or both of the flanking ITRs comprises a sequence selected from the group consisting of one or more of the sequences shown in Table 3 .
A ceDNA vector according to any one of claims 1 to 7 .
前記隣接するＩＴＲの一方又は両方が、前記Ｂ及びＢ’領域によって形成されるステムループ構造の全部又は一部の欠失をもたらす、欠失、挿入、及び／又は置換によって修飾されている；又は
前記隣接するＩＴＲの一方又は両方が、前記Ｃ及びＣ’領域によって形成されるステムループ構造の全部又は一部の欠失をもたらす、欠失、挿入、及び／又は置換によって修飾されている；又は
前記隣接するＩＴＲの一方又は両方が、前記Ｂ及びＢ’領域によって形成されるステムループ構造の一部、並びに／又は前記Ｃ及びＣ’領域によって形成されるステムループ構造の一部の欠失をもたらす、欠失、挿入、及び／又は置換によって修飾されている；又は
前記隣接するＩＴＲの一方又は両方が、野生型ＩＴＲにおいて、前記Ｂ及びＢ’領域によって形成される第１のステムループ構造と、前記Ｃ及びＣ’領域によって形成される第２のステムループ構造とを含む領域に、単一のステムループ構造を含む；又は
前記隣接するＩＴＲの一方又は両方が、野生型ＩＴＲにおいて、前記Ｂ及びＢ’領域によって形成される第１のステムループ構造と、前記Ｃ及びＣ’領域によって形成される第２のステムループ構造とを含む領域に、単一のステム及び２つのループを含む；又は
前記隣接するＩＴＲの一方又は両方が、野生型ＩＴＲにおいて、前記Ｂ及びＢ’領域によって形成される第１のステムループ構造と、前記Ｃ及びＣ’領域によって形成される第２のステムループ構造とを含む領域に、単一のステム及び単一のループを含む、
請求項１～１０のいずれか一項に記載のｃｅＤＮＡベクター。 one or both of the flanking ITRs are modified by a deletion, insertion, and/or substitution in at least one of the ITR regions selected from the group consisting of A, A', B, B', C, C', D, and D' ;
one or both of the flanking ITRs have been modified by deletion, insertion, and/or substitution, resulting in the loss of all or part of the stem-loop structure formed by the B and B'regions; or
one or both of the flanking ITRs have been modified by deletion, insertion, and/or substitution, resulting in the loss of all or part of the stem-loop structure formed by the C and C'regions; or
one or both of the flanking ITRs have been modified by a deletion, insertion, and/or substitution that results in the loss of a portion of the stem-loop structure formed by the B and B' regions and/or a portion of the stem-loop structure formed by the C and C'regions; or
one or both of the flanking ITRs comprises a single stem-loop structure in a region that, in the wild-type ITR, comprises a first stem-loop structure formed by the B and B' regions and a second stem-loop structure formed by the C and C'regions; or
one or both of the flanking ITRs comprises a single stem and two loops in a region that, in the wild-type ITR, comprises a first stem-loop structure formed by the B and B' regions and a second stem-loop structure formed by the C and C'regions; or
one or both of the flanking ITRs comprises a single stem and a single loop in a region that, in the wild-type ITR, comprises a first stem-loop structure formed by the B and B' regions and a second stem-loop structure formed by the C and C'regions;
A ceDNA vector according to any one of claims 1 to 10 .
A kit comprising a ceDNA vector according to any one of claims 1 to 18 , or a composition according to claim 27 , or a cell according to claim 26 , and instructions for use .
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Family Cites Families (130)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4501729A (en) | 1982-12-13 | 1985-02-26 | Research Corporation | Aerosolized amiloride treatment of retained pulmonary secretions |
| US4946787A (en) | 1985-01-07 | 1990-08-07 | Syntex (U.S.A.) Inc. | N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US5049386A (en) | 1985-01-07 | 1991-09-17 | Syntex (U.S.A.) Inc. | N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| DE3872574D1 (en) | 1987-04-24 | 1992-08-13 | Arturo Broggini | ARTIFICIAL STONES AND METHOD FOR THE PRODUCTION THEREOF. |
| US5549910A (en) | 1989-03-31 | 1996-08-27 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
| US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
| JP3218637B2 (en) | 1990-07-26 | 2001-10-15 | 大正製薬株式会社 | Stable aqueous liposome suspension |
| JP2958076B2 (en) | 1990-08-27 | 1999-10-06 | 株式会社ビタミン研究所 | Multilamellar liposome for gene transfer and gene-captured multilamellar liposome preparation and method for producing the same |
| AU657111B2 (en) | 1990-12-20 | 1995-03-02 | Dana-Farber Cancer Institute | Control of gene expression by ionizing radiation |
| US6605712B1 (en) | 1990-12-20 | 2003-08-12 | Arch Development Corporation | Gene transcription and ionizing radiation: methods and compositions |
| US5364791A (en) | 1992-05-14 | 1994-11-15 | Elisabetta Vegeto | Progesterone receptor having C. terminal hormone binding domain truncations |
| US5571797A (en) | 1994-05-11 | 1996-11-05 | Arch Development Corporation | Method of inducing gene expression by ionizing radiation |
| US5741516A (en) | 1994-06-20 | 1998-04-21 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| US5834306A (en) | 1994-12-23 | 1998-11-10 | Sri International | Tissue specific hypoxia regulated therapeutic constructs |
| US5795587A (en) | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US5738868A (en) | 1995-07-18 | 1998-04-14 | Lipogenics Ltd. | Liposome compositions and kits therefor |
| US5928906A (en) | 1996-05-09 | 1999-07-27 | Sequenom, Inc. | Process for direct sequencing during template amplification |
| US5928638A (en) | 1996-06-17 | 1999-07-27 | Systemix, Inc. | Methods for gene transfer |
| US7098320B1 (en) | 1996-07-29 | 2006-08-29 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
| GB9709421D0 (en) | 1997-05-10 | 1997-07-02 | Zeneca Ltd | Chemical compounds |
| JP4656675B2 (en) | 1997-05-14 | 2011-03-23 | ユニバーシティー オブ ブリティッシュ コロンビア | High rate encapsulation of charged therapeutic agents in lipid vesicles |
| US6709858B1 (en) | 1997-11-03 | 2004-03-23 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Hyperthermic inducible expression vectors for gene therapy and methods of use thereof |
| AU1390699A (en) | 1997-11-17 | 1999-06-07 | Imarx Pharmaceutical Corp. | A method of increasing nucleic acid synthesis with ultrasound |
| US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
| GB9810423D0 (en) | 1998-05-15 | 1998-07-15 | Cancer Res Campaign Tech | Ionizing radiation or diathermy-switched gene therapy vectors and their use in antitumour therapy |
| AU1750400A (en) | 1998-12-04 | 2000-06-26 | Mosaic Technologies, Inc. | Method for the immobilization of oligonucleotides |
| JP2004504806A (en) | 2000-03-01 | 2004-02-19 | アムジエン・インコーポレーテツド | Identification and use of effectors and allosteric molecules to alter gene expression |
| ES2327609T3 (en) | 2000-06-01 | 2009-11-02 | University Of North Carolina At Chapel Hill | PROCEDURES AND COMPOUNDS TO CONTROL THE RELEASE OF RECONBINANT PARVOVIRUS VECTORS. |
| US6716622B2 (en) | 2000-07-18 | 2004-04-06 | Uab Research Foundation | Tissue-specific self-inactivating gene therapy vector |
| WO2002087541A1 (en) | 2001-04-30 | 2002-11-07 | Protiva Biotherapeutics Inc. | Lipid-based formulations for gene transfer |
| FR2824431A1 (en) | 2001-05-03 | 2002-11-08 | Mitsubishi Electric Inf Tech | METHOD AND DEVICE FOR RECEIVING SIGNAL |
| JP2006522158A (en) | 2003-04-03 | 2006-09-28 | アルナイラム ファーマシューティカルズ インコーポレイテッド | iRNA complex |
| WO2004091515A2 (en) | 2003-04-09 | 2004-10-28 | Alnylam Pharmaceuticals, Inc. | iRNA CONJUGATES |
| JP4842821B2 (en) | 2003-09-15 | 2011-12-21 | プロチバ バイオセラピューティクス インコーポレイティッド | Polyethylene glycol modified lipid compounds and uses thereof |
| US7840263B2 (en) | 2004-02-27 | 2010-11-23 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression |
| EP1766035B1 (en) | 2004-06-07 | 2011-12-07 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering rna |
| JP4764426B2 (en) | 2004-06-07 | 2011-09-07 | プロチバ バイオセラピューティクス インコーポレイティッド | Cationic lipids and methods of use |
| US20060051405A1 (en) | 2004-07-19 | 2006-03-09 | Protiva Biotherapeutics, Inc. | Compositions for the delivery of therapeutic agents and uses thereof |
| EP1913011B1 (en) | 2004-08-04 | 2016-11-02 | Alnylam Pharmaceuticals Inc. | Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase |
| SG160326A1 (en) | 2004-11-08 | 2010-04-29 | Univ Yale | Structure-based compound design involving riboswitches |
| JP5292572B2 (en) | 2004-12-27 | 2013-09-18 | サイレンス・セラピューティクス・アーゲー | Coated lipid complexes and their use |
| US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
| US20110172826A1 (en) | 2005-12-14 | 2011-07-14 | Amodei Dario G | Device including altered microorganisms, and methods and systems of use |
| US20110182859A1 (en) | 2010-01-22 | 2011-07-28 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Compositions and methods for therapeutic delivery with microorganisms |
| US8313901B2 (en) | 2005-12-21 | 2012-11-20 | Yale University | Methods and compositions related to the modulation of riboswitches |
| US8324436B2 (en) | 2006-01-03 | 2012-12-04 | Honeywell International Inc. | Gas phase synthesis of 2,3,3,3-tetrafluoro-1-propene from 2-chloro-3,3,3-trifluoro-1-propene |
| US20070190028A1 (en) | 2006-02-13 | 2007-08-16 | Jihong Qu | Method and apparatus for heat or electromagnetic control of gene expression |
| WO2008022309A2 (en) | 2006-08-18 | 2008-02-21 | F. Hoffmann-La Roche Ag | Polyconjugates for in vivo delivery of polynucleotides |
| CA3144493A1 (en) | 2006-10-03 | 2008-04-10 | Arbutus Biopharma Corporation | Lipid containing formulations |
| US9388425B2 (en) | 2006-10-20 | 2016-07-12 | Trustees Of Boston University | Tunable genetic switch for regulating gene expression |
| US20110250138A1 (en) | 2007-08-01 | 2011-10-13 | Alnylam Pharmaceuticals, Inc. | Single-stranded and double-stranded oligonucleotides comprising a metal-chelating ligand |
| CA2708171C (en) | 2007-12-04 | 2018-02-27 | Alnylam Pharmaceuticals, Inc. | Folate conjugates |
| CA2930393C (en) | 2007-12-04 | 2022-11-29 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugates as delivery agents for oligonucleotides |
| WO2009086558A1 (en) | 2008-01-02 | 2009-07-09 | Tekmira Pharmaceuticals Corporation | Improved compositions and methods for the delivery of nucleic acids |
| CA2721333C (en) | 2008-04-15 | 2020-12-01 | Protiva Biotherapeutics, Inc. | Novel lipid formulations for nucleic acid delivery |
| WO2009132131A1 (en) | 2008-04-22 | 2009-10-29 | Alnylam Pharmaceuticals, Inc. | Amino lipid based improved lipid formulation |
| WO2010006282A2 (en) | 2008-07-10 | 2010-01-14 | Serina Therapeutics, Inc. | Polyoxazolines with inert terminating groups, polyoxazolines prepared from protected initiating groups and related compounds |
| WO2010019257A2 (en) | 2008-08-13 | 2010-02-18 | The Johns Hopkins University | Prodrug activation in cancer cells using molecular switches |
| AU2009303345B2 (en) | 2008-10-09 | 2015-08-20 | Arbutus Biopharma Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
| WO2010048536A2 (en) | 2008-10-23 | 2010-04-29 | Alnylam Pharmaceuticals, Inc. | Processes for preparing lipids |
| KR102042721B1 (en) | 2008-11-10 | 2019-11-11 | 알닐람 파마슈티칼스 인코포레이티드 | Novel lipids and compositions for the delivery of therapeutics |
| WO2010054384A1 (en) | 2008-11-10 | 2010-05-14 | Alnylam Pharmaceuticals, Inc. | Lipids and compositions for the delivery of therapeutics |
| EP2391343B1 (en) | 2009-01-29 | 2017-03-01 | Arbutus Biopharma Corporation | Improved lipid formulation for the delivery of nucleic acids |
| CA3042927C (en) | 2009-05-05 | 2022-05-17 | Arbutus Biopharma Corporation | Lipid compositions for the delivery of therapeutic agents |
| KR20230098713A (en) | 2009-06-10 | 2023-07-04 | 알닐람 파마슈티칼스 인코포레이티드 | Improved lipid formulation |
| JP5766188B2 (en) | 2009-07-01 | 2015-08-19 | プロチバ バイオセラピューティクス インコーポレイティッド | Lipid formulations for delivering therapeutic agents to solid tumors |
| US8569256B2 (en) | 2009-07-01 | 2013-10-29 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
| EP2467357B1 (en) | 2009-08-20 | 2016-03-30 | Sirna Therapeutics, Inc. | Novel cationic lipids with various head groups for oligonucleotide delivery |
| US9222086B2 (en) | 2009-09-23 | 2015-12-29 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing genes expressed in cancer |
| WO2011053896A2 (en) | 2009-10-30 | 2011-05-05 | University Of Miami | Hypoxia regulated conditionally silenced aav expressing angiogenic inducers |
| US9697460B2 (en) | 2009-11-30 | 2017-07-04 | Trustees Of Boston University | Biological analog-to-digital and digital-to-analog converters |
| US20130022649A1 (en) | 2009-12-01 | 2013-01-24 | Protiva Biotherapeutics, Inc. | Snalp formulations containing antioxidants |
| EP3296398A1 (en) | 2009-12-07 | 2018-03-21 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
| EP2526113B1 (en) | 2010-01-22 | 2016-08-10 | Sirna Therapeutics, Inc. | Post-synthetic chemical modification of rna at the 2'-position of the ribose ring via "click" chemistry |
| WO2011141704A1 (en) | 2010-05-12 | 2011-11-17 | Protiva Biotherapeutics, Inc | Novel cyclic cationic lipids and methods of use |
| CA2799091A1 (en) | 2010-05-12 | 2011-11-17 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods of use thereof |
| DK2575767T3 (en) | 2010-06-04 | 2017-03-13 | Sirna Therapeutics Inc | HOWEVER UNKNOWN LOW MOLECULAR CATIONIC LIPIDS TO PROCESS OIGONUCLEOTIDES |
| US9006417B2 (en) | 2010-06-30 | 2015-04-14 | Protiva Biotherapeutics, Inc. | Non-liposomal systems for nucleic acid delivery |
| US20130323269A1 (en) | 2010-07-30 | 2013-12-05 | Muthiah Manoharan | Methods and compositions for delivery of active agents |
| HRP20220695T1 (en) | 2010-08-31 | 2022-07-08 | Glaxosmithkline Biologicals Sa | Pegylated liposomes for delivery of immunogen-encoding rna |
| US9290760B2 (en) | 2010-09-15 | 2016-03-22 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| EP3144015B1 (en) | 2010-09-20 | 2021-06-02 | Sirna Therapeutics, Inc. | Low molecular weight cationic lipids for oligonucleotide delivery |
| AU2011307277A1 (en) | 2010-09-30 | 2013-03-07 | Merck Sharp & Dohme Corp. | Low molecular weight cationic lipids for oligonucleotide delivery |
| JP2013545727A (en) | 2010-10-21 | 2013-12-26 | メルク・シャープ・アンド・ドーム・コーポレーション | Novel low molecular weight cationic lipids for oligonucleotide delivery |
| WO2012068187A1 (en) | 2010-11-19 | 2012-05-24 | Merck Sharp & Dohme Corp. | Poly(amide) polymers for the delivery of oligonucleotides |
| DK3202760T3 (en) | 2011-01-11 | 2019-11-25 | Alnylam Pharmaceuticals Inc | PEGYLED LIPIDS AND THEIR USE FOR PHARMACEUTICAL SUPPLY |
| GB201107768D0 (en) | 2011-05-10 | 2011-06-22 | Univ Manchester | Riboswitches |
| WO2012162210A1 (en) | 2011-05-26 | 2012-11-29 | Merck Sharp & Dohme Corp. | Ring constrained cationic lipids for oligonucleotide delivery |
| US9222093B2 (en) | 2011-06-30 | 2015-12-29 | The University Of Hong Kong | Two-way, portable riboswitch mediated gene expression control device |
| RU2014104090A (en) | 2011-07-06 | 2015-08-20 | Новартис Аг | LIPOSOMES WITH AN EFFECTIVE N: P RATIO FOR DELIVERY OF PHK MOLECULES |
| WO2013016058A1 (en) | 2011-07-22 | 2013-01-31 | Merck Sharp & Dohme Corp. | Novel bis-nitrogen containing cationic lipids for oligonucleotide delivery |
| ES2705498T3 (en) | 2011-08-31 | 2019-03-25 | Glaxosmithkline Biologicals Sa | Pegylated liposomes for administration of RNA encoding immunogen |
| JP6250543B2 (en) | 2011-09-27 | 2017-12-20 | アルニラム・ファーマシューティカルズ・インコーポレーテッド | Dialiphatic substituted PEGylated lipids |
| US9463247B2 (en) | 2011-12-07 | 2016-10-11 | Alnylam Pharmaceuticals, Inc. | Branched alkyl and cycloalkyl terminated biodegradable lipids for the delivery of active agents |
| CA2856742A1 (en) | 2011-12-07 | 2013-06-13 | Alnylam Pharmaceuticals, Inc. | Biodegradable lipids for the delivery of active agents |
| US20140308304A1 (en) | 2011-12-07 | 2014-10-16 | Alnylam Pharmaceuticals, Inc. | Lipids for the delivery of active agents |
| EP2792367A4 (en) | 2011-12-12 | 2015-09-30 | Kyowa Hakko Kirin Co Ltd | Lipid nanoparticles for drug delivery system containing cationic lipids |
| WO2013116126A1 (en) | 2012-02-01 | 2013-08-08 | Merck Sharp & Dohme Corp. | Novel low molecular weight, biodegradable cationic lipids for oligonucleotide delivery |
| EP3988104A1 (en) | 2012-02-24 | 2022-04-27 | Arbutus Biopharma Corporation | Trialkyl cationic lipids and methods of use thereof |
| EP2830594B1 (en) | 2012-03-27 | 2018-05-09 | Sirna Therapeutics, Inc. | DIETHER BASED BIODEGRADABLE CATIONIC LIPIDS FOR siRNA DELIVERY |
| EP2879718B1 (en) | 2012-08-06 | 2023-06-07 | Alnylam Pharmaceuticals, Inc. | Processes for the preparation of carbohydrate conjugated rna agents |
| EP2914731B1 (en) | 2012-11-01 | 2019-09-11 | California Institute of Technology | Reversible gene expression |
| DK3019200T3 (en) | 2013-07-11 | 2022-06-20 | Alnylam Pharmaceuticals Inc | OLIGONUCLEOTIDE-LIGAND CONJUGATES AND METHOD OF PREPARATION |
| US20160151284A1 (en) | 2013-07-23 | 2016-06-02 | Protiva Biotherapeutics, Inc. | Compositions and methods for delivering messenger rna |
| KR102096796B1 (en) | 2013-10-22 | 2020-05-27 | 샤이어 휴먼 지네틱 테라피즈 인크. | Lipid formulations for delivery of messenger rna |
| US9365610B2 (en) | 2013-11-18 | 2016-06-14 | Arcturus Therapeutics, Inc. | Asymmetric ionizable cationic lipid for RNA delivery |
| AU2014348212C1 (en) | 2013-11-18 | 2018-11-29 | Arcturus Therapeutics, Inc. | Ionizable cationic lipid for RNA delivery |
| WO2015095346A1 (en) | 2013-12-19 | 2015-06-25 | Novartis Ag | Lipids and lipid compositions for the delivery of active agents |
| US10059655B2 (en) | 2013-12-19 | 2018-08-28 | Novartis Ag | Lipids and lipid compositions for the delivery of active agents |
| HUE060907T2 (en) | 2014-06-25 | 2023-04-28 | Acuitas Therapeutics Inc | Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids |
| WO2016011089A1 (en) | 2014-07-14 | 2016-01-21 | President And Fellows Of Harvard College | Compositions comprising riboregulators and methods of use thereof |
| CA2968060C (en) | 2014-11-18 | 2023-06-20 | Arcturus Therapeutics, Inc. | Ionizable cationic lipid for rna delivery |
| WO2016121073A1 (en) | 2015-01-30 | 2016-08-04 | 株式会社 日立ハイテクノロジーズ | Pattern matching device and computer program for pattern matching |
| GB201506507D0 (en) | 2015-04-16 | 2015-06-03 | Univ Wageningen | Riboswitch inducible gene expression |
| WO2017004143A1 (en) | 2015-06-29 | 2017-01-05 | Acuitas Therapeutics Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
| EP3736261B1 (en) | 2015-09-17 | 2023-10-11 | ModernaTX, Inc. | Compounds and compositions for intracellular delivery of therapeutic agents |
| CA3003055C (en) | 2015-10-28 | 2023-08-01 | Acuitas Therapeutics, Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
| WO2017099823A1 (en) | 2015-12-10 | 2017-06-15 | Modernatx, Inc. | Compositions and methods for delivery of therapeutic agents |
| WO2017117528A1 (en) | 2015-12-30 | 2017-07-06 | Acuitas Therapeutics, Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
| US10550440B2 (en) | 2016-02-26 | 2020-02-04 | Arizona Board Of Regents On Behalf Of Arizona State University | Synthetic translation-sensing riboswitches and uses thereof |
| MA45478A (en) | 2016-04-11 | 2019-02-20 | Arbutus Biopharma Corp | TARGETED NUCLEIC ACID CONJUGATE COMPOSITIONS |
| US20180020547A1 (en) | 2016-07-13 | 2018-01-18 | Alcatel-Lucent Canada Inc. | Underlying recessed component placement |
| WO2018026762A1 (en) | 2016-08-01 | 2018-02-08 | Arizona Board Of Regents On Behalf Of Arizona State University | Ultraspecific riboregulators having robust single-nucleotide specificity and in vitro and in vivo uses thereof |
| US10604552B2 (en) | 2016-10-17 | 2020-03-31 | Northwestern University | Generation of novel metabolite-responsive transcription regulator biosensors |
| CN111818942A (en) * | 2018-02-14 | 2020-10-23 | 世代生物公司 | Non-viral DNA vectors and their use for the production of antibodies and fusion proteins |
| SG11202007621TA (en) * | 2018-02-22 | 2020-09-29 | Generation Bio Co | Controlled expression of transgenes using close-ended dna (cedna) vectors |
| EP3810782A2 (en) * | 2018-06-22 | 2021-04-28 | Asklepios Biopharmaceutical, Inc. | Vectors for gene delivery that persist within cells |
-
2021
- 2021-03-24 CA CA3172591A patent/CA3172591A1/en active Pending
- 2021-03-24 EP EP21718770.7A patent/EP4127186A1/en active Pending
- 2021-03-24 US US17/913,482 patent/US20230134550A1/en active Pending
- 2021-03-24 AU AU2021244559A patent/AU2021244559A1/en active Pending
- 2021-03-24 JP JP2022557747A patent/JP2023520763A/en active Pending
- 2021-03-24 MX MX2022011806A patent/MX2022011806A/en unknown
- 2021-03-24 WO PCT/US2021/023898 patent/WO2021195218A1/en unknown
- 2021-03-24 CN CN202180037593.7A patent/CN115667531A/en active Pending
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