Non-immunogenic and nuclease resistant nucleic acid origami devices and compositions thereof

A nucleic acid origami device comprising a scaffold strand and a plurality of staple strands, having the structure A, B C or D, wherein:

• in the structure A:
• (i) one of the staple strands comprises either (a) an aptamer domain capable of binding to a binding partner;
• (b) an oligonucleotide capable of binding a DNA binding protein;
• or (c) an oligonucleotide attached to a nano-antenna capable of receiving an electromagnetic field, or one of the staple strands comprises an aptamer domain of (a) and another of the staple strands comprises an oligonucleotide of (b) or (c);
• (ii) another of the staple strands comprises a latch domain hybridized or bound to said aptamer domain of (a) or oligonucleotide of (b) or (c), the latch domain sequence being selected such that the aptamer domain of (a) is capable of binding to the binding partner such that the binding partner displaces the latch domain, or the latch domain is capable of hybridizing with an external oligonucleotide selected such that the external oligonucleotide displaces the aptamer domain;
• said latch domain is linked to a binding partner that is selected such that it has a first configuration under a first condition and a different second configuration under a different second condition, and the aptamer of (a) or the oligonucleotide of (b) is capable of binding to the binding partner having the first configuration but incapable of binding to the binding partner having the second configuration such that the latch domain is displaced from the aptamer of (a) or the oligonucleotide of (b) when the binding partner transitions from the first to the second configuration;
• or the nano-antenna of (c), upon receipt of said electromagnetic field, undergoes inductive coupling and subsequent heating thereby displacing the latch domain from the oligonucleotide of (c);
• and
• (iii) the aptamer domain of (a) or the oligonucleotide of (b) or (c), and the latch domain, when hybridized or bound to one another, hold the device in a closed configuration;
• and the device transitions to an open configuration when said aptamer domain or oligonucleotide, and the latch domain, are not hybridized or bound to one another,
• in the structure B:
• (i) one of the staple strands comprises a first aptamer domain capable of binding to a first binding partner;
• (ii) another of the staple strands comprises a second aptamer domain capable of binding to a second binding partner;
• (iii) still another of the staple strands comprises a first latch domain hybridized to the first aptamer domain, the sequence of the first latch domain being selected such that the first aptamer domain is capable of binding to the first binding partner such that the first binding partner displaces the first latch domain, or the first latch domain is capable of hybridizing with an external oligonucleotide selected such that the external oligonucleotide displaces the first aptamer domain;
• (iv) yet another of the staple strands comprises a second latch domain hybridized to the second aptamer domain, the second latch domain sequence being selected such that the second aptamer domain is capable of binding to the second binding partner such that the second binding partner displaces the second latch domain, or the second latch domain is capable of hybridizing with an external oligonucleotide selected such that the external oligonucleotide displaces the second aptamer domain;
• and
• (v) said nucleic acid origami device is in a closed configuration when the first aptamer domain is hybridized to the first latch domain and/or the second aptamer domain is hybridized to the second latch domain;
• and the device transitions to an open configuration when the first aptamer domain is not hybridized to the first latch domain and the second aptamer domain is not hybridized to the second latch domain,
• in the structure C:
• (i) two of the staple strands each comprises a latch domain linked to an oligonucleotide capable of hybridizing with an external oligonucleotide;
• and
• said nucleic acid origami device is in an open configuration when each oligonucleotide capable of hybridizing with an external oligonucleotide is not hybridized to said external oligonucleotide;
• and the device transitions to a closed configuration when each oligonucleotide capable of hybridizing with an external oligonucleotide is hybridized to each one of said external oligonucleotide,
• in the structure D;
• (i) one of the staple strands comprises an intrinsic oligonucleotide capable of hybridizing with an external soluble oligonucleotide and an oligonucleotide linked to a latch domain;
• (ii) two of the staple strands each comprises a latch domain linked to a first or a second oligonucleotide, wherein the first oligonucleotide is capable of hybridizing to the second oligonucleotide and to the intrinsic oligonucleotide;
• (iii) each one of the first and second oligonucleotide is hybridized to one intrinsic oligonucleotide and is selected such that the intrinsic oligonucleotide is capable of hybridizing to the external soluble oligonucleotide such that the external soluble oligonucleotide displaces the intrinsic oligonucleotide and the first and second oligonucleotide hybridize to each other;
• and
• (iv) said nucleic acid origami device is in an open configuration when each one of the first and second oligonucleotide is hybridized to said intrinsic oligonucleotide;
• and the device transitions to a closed configuration when the first and second oligonucleotide is not hybridized to said intrinsic oligonucleotide and is instead hybridized to each other,
• wherein
• said nucleic acid origami device is either alkylated, acylated or hydroxylated, or interacts with a compound capable of non-covalently binding to the major- or minor-groove of a double stranded nucleic acid, and therefore is resistant to nucleases, and/or
• said nucleic acid origami device lacks TLR9 recognition elements or the TLR9 recognition elements of said nucleic acid origami device are masked or modified and therefore said nucleic acid origami device is non-immunogenic.