Constructs and methods for regulation of a target molecule

Abstract

Aspects of the present disclosure generally relate to constructs and methods for regulation of a biological target molecule. In some embodiments, the construct comprises a thermosensitive element and a signal transducing element. In some embodiments, transduction of a signal, for example a wireless or tissue penetrating signal, to the thermosensitive element results in a conformational change, wherein the conformational change allows expression or regulation of a target molecule.

Description

CONSTRUCTS AND METHODS FOR REGULATION OF A TARGET MOLECULEINCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 623,126, filed on January 19, 2024, and U.S. Provisional Application No. 63 / 699,002, filed on September 25, 2024, the content of each of which is herein expressly incorporated by reference in its entirety.FIELD

[0002] Aspects of the present disclosure relate generally to constructs and methods for regulation of a target molecule. More specifically, some aspects of the present disclosure are related to constructs and methods for magneto-genetic regulation of a biological target molecule.BACKGROUND

[0003] Much work has been done to collect and process biological information, but interfaces between biological and non-biological systems, for example, the interface between biological and chemical, light, electrical, or magnetic systems, remains underdeveloped. In particular, the interface between biological and chemical, light, electrical, or magnetic systems for use in diagnosing and treating detrimental biological conditions, such a disease, remains underdeveloped.SUMMARY

[0004] For purposes of summarizing the disclosure and the advantages achieved over the prior art, certain objects and advantages of the disclosure are described herein. Not all such objects or advantages may be achieved in any particular embodiment. Thus, for example, those skilled in the art will recognize that the invention may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objects or advantages as may be taught or suggested herein.

[0005] All of these embodiments are intended to be within the scope of the invention herein disclosed. These and other embodiments will become readily apparent to those skilled in the art from the following detailed description of the preferred embodimentshaving reference to the attached figures, the invention not being limited to any particular preferred embodiment(s) disclosed.

[0006] In one aspect, a construct for expression or regulation of a target molecule is described. In some embodiments, the construct includes: a thermosensitive element, and a signal transducing element; wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element; and wherein the conformational change in the thermosensitive element allows expression or regulation of a target molecule. In some embodiments, the thermosensitive element comprises a nucleic acid. In some embodiments, the nucleic acid is RNA or DNA. In some embodiments, the thermosensitive element comprises a protein. In some embodiments, the thermosensitive element comprises one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, the thermosensitive element comprises one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5’ cap, ribosomal translation start codon, 3’ termini, 3’ poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0007] In some embodiments, the signal transducing element comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element comprises a ferritin nanoparticle. In some embodiments, the signal transducing element comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an ironoxide nanoparticle. In some embodiments, the signal comprises a tissue penetrating signal. In some embodiments, the signal comprises a wireless signal. In some embodiments, the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In some embodiments, the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In some embodiments, the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz. In some embodiments, the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m. In some embodiments, the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In some embodiments, transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element. In some embodiments, the temperature increases by between about 0.1 °C and 35 °C. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element. In some embodiments, the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In some embodiments, the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.

[0008] In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more genetic elements selected from: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, the temperature or free energy (AG) of the thermosensitive element decreases following cessation of the signal. In some embodiments, the construct further comprises a linker. In some embodiments, regulation of a target molecule comprises obstruction and / or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In some embodiments, regulation of a target molecule comprises obstruction and / or de-obstruction ofone or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, regulation of a target molecule comprises obstruction and / or de-obstruction of one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0009] In another aspect, a construct for programmed conformational change is described. In some embodiments, the construct includes: a thermosensitive element, and a signal transducing element; wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; and wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element. In some embodiments, the conformational change in the thermosensitive element obstructs one or more genetic elements. In some embodiments, conformational change in the thermosensitive element de-obstructs one or more genetic elements. In some embodiments, the thermosensitive element comprises a nucleic acid. In some embodiments, the nucleic acid is RNA or DNA. In some embodiments, the thermosensitive element comprises a protein. In some embodiments, the thermosensitive element comprises one or more genetic elements selected from: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translationinitiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, the thermosensitive element comprises one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0010] In some embodiments, the signal transducing element comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element comprises a ferritin nanoparticle. In some embodiments, the signal transducing element comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an iron oxide nanoparticle. In some embodiments, the signal comprises a tissue penetrating signal. In some embodiments, the signal comprises a wireless signal. In some embodiments, the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In some embodiments, the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In some embodiments, the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz. In some embodiments, the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m. In some embodiments, the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In some embodiments, transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element. In some embodiments, the temperature increases by between about 0.1 °C and 35 °C. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element. In someembodiments, the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In some embodiments, the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.

[0011] In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more genetic elements from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpinloop structure, and any combination thereof. In some embodiments, obstruction and / or deobstruction of one or more genetic elements alters expression and / or regulation of one or more target molecules. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In some embodiments, obstruction and / or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element alters expression and / or regulation of one or more target molecules. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), capindependent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof, alters expression and / or regulation of one or more target molecules. In some embodiments, the temperature or free energy (AG) of the thermosensitive element decreases following cessation of the signal. In some embodiments, the construct further comprises a linker.

[0012] In another aspect, a gene expression construct is described. In some embodiments, the gene expression construct includes: a thermosensitive nucleic acid, and amagnetically-susceptible nanoparticle; wherein the thermosensitive nucleic acid is configured to change confirmations upon transduction of a signal from the magnetically-susceptible nanoparticle to the thermosensitive nucleic acid. In some embodiments, the thermosensitive element comprises a nucleic acid. In some embodiments, the nucleic acid is RNA or DNA. In some embodiments, the thermosensitive element comprises a protein. In some embodiments, the thermosensitive element comprises one or more genetic elements selected from: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, the thermosensitive element comprises one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0013] In some embodiments, the signal transducing element comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element comprises a ferritin nanoparticle. In some embodiments, the signal transducing element comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an iron oxide nanoparticle. In some embodiments, the signal comprises a tissue penetrating signal. In some embodiments, the signal comprises a wireless signal. In some embodiments, the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In some embodiments, the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In someembodiments, the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz. In some embodiments, the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m. In some embodiments, the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In some embodiments, transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element. In some embodiments, the temperature increases by between about 0.1 °C and 35 °C. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element. In some embodiments, the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In some embodiments, the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.

[0014] In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more genetic elements selected from: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, obstruction and / or de-obstruction of one or more genetic elements alters expression and / or regulation of one or more genes. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In some embodiments, obstruction and / or deobstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element, alters expression and / or regulation of one or more genes. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In some embodiments, obstruction and / or deobstruction of one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof, alters expression and / or regulation of one or more genes. In some embodiments, the temperature or free energy (AG) of the thermosensitive element decreases following cessation of the signal. In some embodiments, the construct further comprises a linker.

[0015] In another aspect, a method of expressing or regulating a target molecule is described. In some embodiments, the method includes administering a construct for expression or regulation of a target molecule to a subject, the construct including: a thermosensitive element, and a signal transducing element; and applying a signal to the signal transducing element. In some embodiments, transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element. In some embodiments, the conformational change in the thermosensitive element alters expression and / or regulation of a target molecule. In some embodiments, altered expression and / or regulation of a target molecules activates and / or deactivates one or more molecular processes. In some embodiments, the molecular process comprises a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof. In some embodiments, the thermosensitive element comprises a nucleic acid. In some embodiments, the nucleic acid is RNA or DNA. In some embodiments, the thermosensitive element comprises a protein. In some embodiments, thethermosensitive element comprises one or more genetic elements selected from: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, the thermosensitive element comprises one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0016] In some embodiments, the signal transducing element comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element comprises a ferritin nanoparticle. In some embodiments, the signal transducing element comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an iron oxide nanoparticle. In some embodiments, the signal comprises a tissue penetrating signal. In some embodiments, the signal comprises a wireless signal. In some embodiments, the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In some embodiments, the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In some embodiments, the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz. In some embodiments, the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m. In some embodiments, the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In some embodiments, transduction of a signal to the thermosensitive element results in ballistic heat transfer fromthe signal transducing element to the thermosensitive element. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element. In some embodiments, the temperature increases by between about 0.1 °C and 35 °C. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element. In some embodiments, the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In some embodiments, the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.

[0017] In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more genetic elements selected from: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, obstruction and / or de-obstruction of one or more genetic elements alters expression and / or regulation of one or more genes. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In some embodiments, obstruction and / or deobstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element, alters expression and / or regulation of one or more genes. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), capindependent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof, alters expression and / or regulation of one or-l imore genes. In some embodiments, the temperature or free energy (AG) of the thermosensitive element decreases following cessation of the signal.

[0018] In another aspect, a method of programed conformational change is described. In some embodiments, the method includes applying a signal to a signal transducing element; wherein transduction of the signal to a thermosensitive element causes a conformational change in the thermosensitive element. In some embodiments, the conformational change in the thermosensitive element allows expression or regulation of a target molecule. In some embodiments, the method further comprises monitoring expression or regulation of the target molecule. In some embodiments, altered expression or regulation of the target molecule indicates ballistic energy transfer from the signal transducing element to the thermosensitive element. In some embodiments, altered expression and / or regulation of a target molecules activates and / or deactivates one or more molecular processes. In some embodiments, the molecular process comprises a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof. In some embodiments, the thermosensitive element comprises a nucleic acid. In some embodiments, the nucleic acid is RNA or DNA. In some embodiments, the thermosensitive element comprises a protein. In some embodiments, the thermosensitive element comprises one or more genetic elements selected from: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, the thermosensitive element comprises one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loopstructure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0019] In some embodiments, the signal transducing element comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element comprises a ferritin nanoparticle. In some embodiments, the signal transducing element comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an iron oxide nanoparticle. In some embodiments, the signal comprises a tissue penetrating signal. In some embodiments, the signal comprises a wireless signal. In some embodiments, the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In some embodiments, the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In some embodiments, the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz. In some embodiments, the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m. In some embodiments, the signal comprises an alternating magnetic field at a field strength of about 10 kA / m and about 20 kA / m. In some embodiments, transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element. In some embodiments, temperature increases by between about 0.1 °C and 35 °C. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element. In some embodiments, the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In some embodiments, the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.

[0020] In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs of one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers(CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In some embodiments, obstruction and / or de-obstruction of one or more genetic elements alters expression and / or regulation of one or more genes. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In some embodiments, obstruction and / or deobstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element, alters expression and / or regulation of one or more genes. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), capindependent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In some embodiments, obstruction and / or deobstruction of one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof, alters expression and / or regulation of one or more genes. In some embodiments, the temperature or free energy (AG) of the thermosensitive element decreases following cessation of the signal.

[0021] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodimentsdescribed in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In addition to the features described above, additional features and variations will be readily apparent from the following descriptions of the drawings and exemplary embodiments. It is to be understood that these drawings depict typical embodiments and are not intended to be limiting in scope.

[0023] FIG. 1 is an illustration depicting a construct for expression or regulation of a target molecule, according to some embodiments.

[0024] FIG. 2 is an illustration depicting a construct for programmed conformational change, according to some embodiments.

[0025] FIG. 3 is an illustration depicting a gene expression construct, according to some embodiments.

[0026] FIG. 4 is a flow chart of a method of expressing or regulating a target molecule, according to some embodiments.

[0027] FIG. 5 is a flow chart of a method of programmed conformational change, according to some embodiments.

[0028] FIG. 6 is an illustration depicting a construct including a ferritin-RNA- Binding protein (RBP), according to some embodiments.

[0029] FIG. 7 is an illustration depicting a construct including a ferritin-stem-loop- binding-protein (SLBP) fusion peptide, according to some embodiments.

[0030] FIG. 8 is an illustration depicting a construct including a ferritin-MS2 Coat Protein (MCP) fusion peptide, according to some embodiments.

[0031] FIG. 9A is a schematic showing a system for regulation of a target molecule, according to some embodiments.

[0032] FIG. 9B is a schematic showing a system for regulation of a target molecule, according to some embodiments.

[0033] FIG. 10 is a schematic showing a construct comprising an NP-RNAT or Ferritin-RNAT based AND GATE, according to some embodiments.

[0034] FIG. 11A is a schematic showing a construct for expressing a toehold switch trigger RNA, according to some embodiments.

[0035] FIG. 11B is a schematic showing a construct comprising an aptamer having a disjointed RNA thermometer (RNAT) and toehold switch components, according to some embodiments.

[0036] FIG. 11C is a schematic showing activation of a construct comprising an aptamer having a disjointed RNA thermometer (RNAT) and toehold switch components, according to some embodiments.

[0037] FIG. 12A is a schematic showing activation of a construct comprising an aptamer having an unified RNA thermometer (RNAT) and toehold switch components, according to some embodiments.

[0038] FIG. 12B is a schematic showing activation of a construct comprising an aptamer having an unified RNA thermometer (RNAT) and toehold switch components, according to some embodiments.

[0039] FIG. 12C is a schematic showing a construct for expressing a toehold switch trigger RNA, according to some embodiments.

[0040] FIG. 12D is a schematic showing a construct comprising an aptamer having an unified RNA thermometer (RNAT) and toehold switch components, according to some embodiments.

[0041] FIG. 13A is a schematic depicting Ferritin-RNA-Binding Protein (RBP) and aptamer synthesis.

[0042] FIG. 13B is a schematic showing Ferritin-RNA-Binding Protein (RBP) and aptamer coupling.

[0043] FIG. 13C is a pair of schematics showing toehold switch activation (top) and RNA thermometer (RNAT) activation (bottom).

[0044] FIG. 13D is a schematic showing RNA thermometer (RNAT) - toehold switch activation.

[0045] FIG. 14 is an illustration showing a plasmid for expressing a construct according to some embodiments disclosed herein.

[0046] FIG. 15 is a schematic showing a plasmid layout within a system architecture utilizing the constructs and methods according to some embodiments disclosed herein.

[0047] FIG. 16 is a graph depicting expression and luminescence from a prokaryotic construct according to some embodiments disclosed herein under no heat, heat shock, and alternating magnetic field induction.

[0048] FIG. 17 is a graph depicting expression and luminescence from an eukaryotic construct according to some embodiments disclosed herein under alternating magnetic field induction.

[0049] FIG. 18 is a graph depicting expression and luminescence from an eukaryotic construct according to some embodiments disclosed herein under alternating magnetic field induction.

[0050] FIG. 19 is a graph depicting fold change in luminescence from a construct according to some embodiments disclosed herein under alternating magnetic field induction.

[0051] FIG. 20 is a graph depicting the change in luminescence from a construct according to some embodiments disclosed herein under alternating magnetic field induction.

[0052] FIG. 21 is an image of an in silico-designed construct according to some embodiments disclosed herein.

[0053] FIG. 22 is a schematic showing an in-silico designed variant in the “Off’ configuration according to some embodiments disclosed herein.

[0054] FIG. 23 is a schematic showing an in-silico designed variant in the “On” configuration according to some embodiments disclosed herein.DETAILED DESCRIPTION

[0055] Current chemo-genetic (chemical-based gene regulation) or optogenetic (light-based gene regulation) mechanisms are slow and have limited spatiotemporal resolution or tissue penetrance. Current magneto-genetic (magnetic-based gene regulation) mechanisms have temporal resolutions that are several orders of magnitudes too large for many synthetic biology applications. Additionally, they have nominal sensitivity and spatial resolution that limits the amplitude and frequency of the response. Moreover, these techniques utilize the signaling pathways of various other processes and are thus very susceptible to noise and unintended activation / deactivation. Accordingly, some embodiments of the present disclosureare directed to constructs having an improved biological-non-biological interface and methods of use thereof. Some embodiments of the present disclosure are directed to constructs providing bio-orthogonal signaling, i.e., a signaling method that is independent and undisturbed by normal biological processes. In some embodiments, the construct comprises a molecular thermometer. In some embodiments, the constructs is a magneto-genetic system that provides spatiotemporal control or regulation of a target molecule. In some embodiments, the target molecule is a biological molecule.Definitions

[0056] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs. It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed.

[0057] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0058] The articles “a” and “an” are used herein to refer to one or to more than one (for example, at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0059] Language of degree used herein, such as the terms “approximately,” “about,” “generally,” and “substantially” is meant to indicate a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by as much as 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.

[0060] Throughout this specification, unless the context requires otherwise, the words “comprise,” “comprises,” and “comprising” will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements. By “consisting of’ is meant including, and limited to, whatever follows the phrase “consisting of.” Thus, the phrase “consisting of’ indicates that the listed elements are required or mandatory, and that no other elements may be present. By “consisting essentially of’ is meant including any elements listed after the phrase and limited to other elements that do not interfere with or contribute to the activity or action specified inthe disclosure for the listed elements. Thus, the phrase “consisting essentially of’ indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they materially affect the activity or action of the listed elements.

[0061] As used herein, the term “nucleotide “has its broad, plain, and ordinary meaning including, for example, referring to a phosphate ester of a nucleoside, as a monomer unit or within a nucleic acid. “Nucleotide 5 ’-triphosphate” refers to a nucleotide with a triphosphate ester group at the 5’ position, and are sometimes denoted as “NTP”, or “dNTP” and “ddNTP” to particularly point out the structural features of the ribose sugar. The triphosphate ester group can include sulfur substitutions for the various oxygens, e.g. alpha. - thio-nucleotide 5 ’-triphosphates. For a review of nucleic acid chemistry, see: Shabarova, Z. and Bogdanov, A. Advanced Organic Chemistry of Nucleic Acids, VCH, New York, 1994.

[0062] As used herein, the term “nucleic acid” has its broad, plain, and ordinary meaning including, for example, referring to natural nucleic acids, artificial or man-made nucleic acids, analogs thereof, or combinations thereof.

[0063] As used herein, the terms “polynucleotide” and “oligonucleotide,” which may be used interchangeably, have their plain and ordinary meaning and may also refer to single-stranded and double-stranded polymers of nucleotide monomers (nucleic acids), including, but not limited to, 2’ -deoxyribonucleotides (nucleic acid) and ribonucleotides (RNA) linked by internucleotide phosphodiester bond linkages, e.g. 3’-5’ and 2’-5’, inverted linkages, e.g. 3’-3’ and 5’-5’, branched structures, circularized nucleic acids, or analog nucleic acids. Polynucleotides have associated counter ions, such as H+, NH4+, trialkylammonium, Mg2+, Na+and the like. A polynucleotide can be composed entirely of deoxyribonucleotides, entirely of ribonucleotides, or chimeric mixtures thereof. Polynucleotides can be comprised of nucleobase and sugar analogs. Polynucleotides typically range in size from a few monomeric units, e.g., 5-40 when they are more commonly frequently referred to in the art as oligonucleotides, to several thousands of monomeric nucleotide units. Unless denoted otherwise, whenever a polynucleotide sequence is represented, it will be understood that the nucleotides are in 5’ to 3’ order from left to right and that “A” denotes deoxyadenosine, “C” denotes deoxycytidine, “G” denotes deoxyguanosine, “T” denotes thymidine, and “U” denotes uracil.

[0064] Polynucleotides are said to have “5’ ends” and “3’ ends” because mononucleotides are reacted to make oligonucleotides in a manner such that the 5’ phosphate of one mononucleotide pentose ring is attached to the 3’ oxygen of its neighbor in one direction via a phosphodiester linkage. Therefore, an end of an oligonucleotide or polynucleotide is referred to as the “5’ end” if its 5’ phosphate is not linked to the 3 ’ oxygen of a mononucleotide pentose ring and as the “3’ end” if its 3’ oxygen is not linked to a 5’ phosphate of a subsequent mononucleotide pentose ring. As used herein, a nucleic acid sequence, even if internal to a larger oligonucleotide, or circularized, also can be said to have 5’ and 3’ ends.

[0065] A “first end” and a “second end” of a polynucleotide refer to the 5’ end or the 3 ’end of the polynucleotide. Either the first end or second end of a polynucleotide can be the 5’ end or the 3’ end of the polynucleotide; the terms “first” and “second” are not meant to denote that the end is specifically the 5’ end or the 3’ end. For example, with circularized nucleic acids, a “first end” and a “second end: may also refer to the end of a response element, gene, or other functional element.

[0066] As used herein, the term “end region” has its broad, plain, and ordinary meaning and may also refer to the region of a polynucleotide located at the 5’ end or the 3’ end. In some embodiments, for example with circularized nucleic acids, the term “end region” may also refer to the end of a response element, gene, or other functional element.

[0067] As used herein, the term “Circular nucleic acids: (CNAs) are has its broad, plain, and ordinary meaning, and may also refer to nucleic acid molecules having a closed loop structure. The circular nucleic acid may be single or double stranded. Circular nucleic acids may refer to natural or synthetic circular DNA and / or RNA molecules. Circular nucleic acids may comprise one or more nicks and / or gaps in one or both strands.

[0068] As used herein, the terms “polypeptide”, “peptide”, and “protein” have their broad, plain, and ordinary meaning and may be used interchangeably. As used herein, these terms may refer to polymers of amino acids of any length. The polymer may be linear, cyclic, or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass amino acid polymers that have been modified, for example, via sulfation, glycosylation, lipidation, acetylation, phosphorylation, iodination, methylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation,transfer-RNA mediated addition of amino acids to proteins such as arginylation, ubiquitination, or any other manipulation, such as conjugation with a labeling component.

[0069] As used herein, the term “aptamer” has its broad, plain, and ordinary meaning including, for example, referring to a nucleic acid based affinity reagent. Aptamers may selectively bind to a specific target, including proteins, peptides, carbohydrates, small molecules, toxins, and even live cells. Aptamers may also enable selective conformational change without target binding. Aptamers assume a variety of shapes due to their tendency to form helices and single-stranded loops. Rather than primary sequence, aptamer binding is determined by its tertiary structure. Aptamer target recognition and binding involve three- dimensional, shape-dependent interactions as well as hydrophobic interactions, base-stacking, and intercalation.

[0070] As used herein, the term “ribozyme” has its broad, plain, and ordinary meaning, including, for example, referring to a catalytically active RNA molecule or RNA- protein complex.

[0071] As used herein, the term “amino acid” has its broad, plain, and ordinary meaning including, for example, referring to either natural and / or unnatural or synthetic amino acids, including glycine and both the D or L optical isomers, and amino acid analogs and peptidomimetics.

[0072] As used herein, the term “conformation,” when used in reference to a molecule or particle, has its broad, plain, and ordinary meaning including, for example, referring to the shape or proportionate dimensions of the molecule or particle. At the molecular level conformation can be characterized by the spatial arrangement of a molecule that results from the rotation of its atoms about their bonds. The conformation of a polypeptide can be characterized in terms of secondary structure, tertiary structure, or quaternary structure. Secondary structure of a polypeptide is the three-dimensional form of local segments of the polypeptide which can be defined, for example, by the pattern of hydrogen bonds between the amino hydrogen and carboxyl oxygen atoms in the peptide backbone or by the regular pattern of backbone dihedral angles in a particular region of the Ramachandran plot for the polypeptide. Tertiary structure of a polypeptide is the three-dimensional shape of a single polypeptide chain backbone including, for example, interactions and bonds of side chains that form domains. Quaternary structure of a polypeptide is the three-dimensional shape andinteraction between the amino acids of multiple polypeptide chain backbones. A polypeptide having a given primary structure can have a native conformation in vitro, whereby the secondary and tertiary structures are the same as or substantially similar to the structures for a polypeptide having the same primary structure in vivo. Optionally the polypeptide can have the same quaternary structure in vivo and in vitro. Alternatively, a polypeptide having a given primary structure can have a denatured conformation in vitro, whereby the secondary, tertiary or quaternary structures are the same as or substantially similar to the structures for a polypeptide having the same primary structure in vivo. Moreover, a polypeptide having a given primary structure can have a denatured conformation in vitro, whereby the polypeptide lacks sufficient stability of secondary, tertiary or quaternary structure to perform biological function observed for a polypeptide having the same primary structure in vivo.

[0073] As used herein, the term “extraneous,” when used in reference to a moiety of a molecule, has its plain and ordinary meaning and may also refer to a moiety that is not present in a natural analog of the molecule. For example, an extraneous label of a polypeptide is a label that is not present on a naturally occurring polypeptide. Similarly, an extraneous reactive moiety that is present on a polypeptide is not found on the polypeptide in its native milieu.

[0074] As used herein, the term “immobilized,” when used in reference to a molecule, has its plain and ordinary meaning and may also refer to the molecule being prevented from diffusing or moving. For example, immobilization can occur due to the molecule being confined at, or attached to, a solid phase. Immobilization can be temporary (e.g., for the duration of one or more steps of a method set forth herein) or permanent. Immobilization can be reversible or irreversible under conditions utilized for a method, system or composition set forth herein.

[0075] As used herein, the term “conjugate” has its plain and ordinary meaning and may also refer to a substance made up of two or more other molecules or compounds that have been chemically joined together. It may also refer to an acid or base that is related to another by the gain or loss of a proton (H+ ion) during a chemical reaction. A “bioconjugate” has its plain and ordinary meaning and may also refer to a conjugate in which one of the molecules or compounds are a biological molecule.

[0076] As used herein, the term “label” has its broad, plain, and ordinary meaning including, for example, referring to a molecule, or a moiety thereof, that provides a detectable characteristic. The detectable characteristic can be, for example, an optical signal such as absorbance of radiation, luminescence (e.g., fluorescence) emission, luminescence lifetime or luminescence polarization; Rayleigh and / or Mie scattering; binding affinity for a ligand or receptor; magnetic properties; electrical properties; charge; mass; radioactivity or the like. Exemplary labels include, without limitation, a fluorophore, luminophore, chromophore, nanoparticle (e.g., gold, silver, carbon nanotubes), heavy atom, radioactive isotope, mass label, charge label, spin label, receptor, ligand, or the like. Nucleic acids can be used as labels and distinguished from each other based on unique nucleotide sequences. The unique nucleotide sequences can function as tags for identifying the molecule or moiety to which the nucleic acid is attached or otherwise associated.

[0077] As used herein, the term “linked,” when used in reference to two objects or moieties, has its plain and ordinary meaning and may also refer to two objects or moieties that are attached to each other via a linker. The linker can be directly attached to an object or moiety, for example, via a covalent or non-covalent bond. The linker may be natural or synthetic.

[0078] As used herein, the term “linker” refers to a moiety that connects two objects to each other. One or both objects can be a molecule, solid support, address, particle or bead. Both objects can be moieties of a molecule, solid support, address, particle or bead. The term can also refer to an atom, moiety or molecule that is configured to react with two objects to form a moiety that connects the two objects. The connection of a linker to one or both objects can be a covalent bond or non-covalent bond. A linker may be configured to provide a chemical or mechanical property to the moiety connecting two objects, such as hydrophobicity, hydrophilicity, electrical charge, polarity, rigidity, or flexibility. A linker may comprise two or more functional groups that facilitate coupling of the linker to the first and second objects. A linker may include a polyfunctional linker such as a homobifunctional linker, heterobifunctional linker, homopolyfunctional linker, or heteropolyfunctional linker. Exemplary compositions for linkers can include, but are not limited to, a polyethylene glycol (PEG), polyethylene oxide (PEO), amino acid, polypeptide, nucleotide, nucleic acid, nucleic acid origami, dendrimer, protein nucleic acid (PNA), polysaccharide, carbon, nitrogen,oxygen, ether, sulfur, or disulfide. A linker can be a bead or particle such as a structured nucleic acid particle.

[0079] As used herein, the terms “moiety” and “element” have their broad, plain, and ordinary meaning including, for example, referring to a component, portion, or part of a molecule. The terms do not necessarily denote the relative size of the component, portion, or part of the molecule compared to the molecule as whole unless indicated otherwise. A moiety or element can contain one or more atom, and will often include distinct a functional or structural group of atoms.

[0080] As used herein, the term “chemogenetic” has its broad, plain, and ordinary meaning including, for example, referring to a property of a process by which macromolecules are engineered to interact with previously unrecognized small molecules. In this aspect, “chemogenetic” may be understood to be similar to optogenetic; however, chemogenetic techniques use chemically engineered molecules and ligands, whereas optogenetic techniques use light and light-sensitive channels known as opsins.

[0081] As used herein, the term “optogenetic” has its broad, plain, and ordinary meaning including, for example, referring to a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In a broader sense, optogenetics also includes methods to record cellular activity with genetically encoded indicators.

[0082] As used herein, the term “magneto-genetic” has its broad, plain, and ordinary, including , for example, referring to a biological technique involving the use of, or application of, one or more magnetic fields to control a molecule. In some cases, magnetic stimulation is transformed into either force (magneto-mechanical genetics) or heat (magnetothermal genetics), which depends on the applied magnetic field. Magneto-genetics is a modulation method that uses a combination of techniques from magnetism and genetics to control activities of individual cells in living tissue - even within freely moving animals and people. This technique is comparable to optogenetics, which is the manipulation of cell behavior using light. In magneto-genetics, magnetic stimulation is used instead of light, a characteristic that allows for a less invasive, less toxic, and wireless modulation of cell activity.Cell activity control is achieved using magnetic compounds such as ferritin or magnetic nanoparticles. These compounds are designed to link to one or more elements such as the ion channels that are genetically expressed on specific cells and thermosensitive elements expressed, delivered, or naturally occurring in specific cells. Control of activity is thus restricted to genetically pre-defined cells and performed in a spatiotemporal-specific manner by magnetic stimulation.

[0083] As used herein, the term “magnetically receptive” has its plain, broad, and ordinary meaning, including, for example, referring to materials that are attracted to magnetic materials. Many materials are magnetically receptive, for example, steel. Magnetically receptive materials may be magnetic or non-magnetic. For example, a non- magnetic magnetically receptive material is attracted to magnetic material but are not magnetic themselves. In contrast, a magnet is both magnetic and magnetically receptive.

[0084] As used herein, the term “target molecule” is a molecule that is intended to be controlled, modified, regulated, or otherwise changed or altered by the methods described herein. As used herein, a target molecule may be any biologically active molecule, depending on the method to be used. In certain embodiments the target molecule is a polypeptide, protein, polynucleotide including a RNA or DNA molecule.

[0085] As used herein, the term “thermosensitive” has its broad, plain, and ordinary meaning including, for example, referring to a property of material being sensitive to, and reactive to, heat or energy.

[0086] As used herein, the term “nerve block” has its broad, plain, and ordinary meaning, including, for example, referring to an interruption of signals traveling along and / or to a nerve. Nerve blocks may be a short-term block, for example, a block lasting minutes, hours or days. Nerve blocks may also persist for weeks, months, or indefinitely.

[0087] As used herein, the term “nerve stimulation” has its broad, plain, and ordinary meaning, including, for example, referring to the provision or enhancement of signals traveling along and / or to a nerve. Nerve stimulation may be a short-term stimulation, for example, stimulation lasting milliseconds, seconds, minutes, hours or days. Nerve stimulation may also persist for weeks, months, or indefinitely.Constructs for expression or regulation of a target molecule

[0088] Some embodiments herein are directed to a construct for expression or regulation of a target molecule. For example, FIG. 1 is an illustration depicting some embodiments of a construct for expression or regulation of a target molecule. In some embodiments, a construct 100 for expression or regulation of a target molecule is disclosed. In some embodiments, the construct 100 comprises a thermosensitive element 101, and a signal transducing element 103. In some embodiments, the thermosensitive element 101 is a thermosensitive nucleic acid. In some embodiments, the thermosensitive element 101 is attached to the signal transducing element 103. In some embodiments, the thermosensitive element 101 is attached to the signal transducing element 103 by a linker.

[0089] In some embodiments, the construct 100 comprises a plurality of thermosensitive elements 101. In some embodiments, each thermosensitive element is identical. In some embodiments, one or more different thermosensitive elements are attached to the signal transducing element. In some embodiments, the thermosensitive element is configured to transduce a signal of a desired type. In some embodiments, the thermosensitive element is configured to receive a signal of a desired type. In some embodiments, the signal transducing element is configured to transduce a signal of a desired type. In some embodiments, the signal transducing element is configured to receive a signal of a desired type. In some embodiments, the signal transducing element and the thermosensitive element are chosen for their ability to transduce and receive a signal of a desired type. In some embodiments, the signal transducing element and the thermosensitive element are chosen for their ability to transduce and receive a signal comprising a desired characteristic, such as a specific signal strength or frequency. In some embodiments, the thermosensitive element is a molecular thermometer. In some embodiments, the thermosensitive element is a nucleic acid. In some embodiments, the thermosensitive element is a nucleic acid thermometer. In some embodiments, the thermosensitive element comprises an RNA binding protein. In some embodiments, the thermosensitive element comprises one or more stem-loop binding proteins. In some embodiments, the thermosensitive element comprises one or more MS2 coat proteins and / or MS2 stem loops. In some embodiments, the thermosensitive element is a protein. In some embodiments the thermosensitive element comprises one or more genetic elements 105. In some embodiments, the one or more genetic elements are genetic regulatory elements. Insome embodiments, the one or more genetic elements are sterically hindered. In some embodiments, the thermosensitive element comprises a first confirmation. In some embodiments, the thermosensitive element comprises a plurality of conformations.

[0090] In some embodiments, the signal transducing element 103 comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element 103 comprises ferritin. In some embodiments, the signal transducing element 103 comprises a ferritin nanoparticle. In some embodiments, the signal transducing element 103 comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an iron oxide nanoparticle.

[0091] A signal 107 applied to the signal transducing element 103 is transduced 109 to the thermosensitive element 101. In some embodiments, the signal is a wireless signal. In some embodiments, the signal is a tissue penetrating signal. In some embodiments, the signal is an electromagnetic signal. In some embodiments, the signal is configured to transduce between the signal transducing element and the thermosensitive element. In some embodiments, the signal is configured to induce a desired conformational change of the thermosensitive particle. In some embodiments, the type of signal is chosen for its suitability for transduction between the signal transducing element and the thermosensitive element. In some embodiments, the strength of the signal is chosen for its ability to induce a desired conformational change upon transduction of the signal from the signal transducing particle to the thermosensitive particle. In some embodiments, the signal is applied intermittently. The signal is transduced 109 to the thermosensitive element 101. Transduction of the signal 109 to the thermosensitive element 101 causes a conformational change 111 in the thermosensitive element. In some embodiments, transduction of the signal causes a plurality of conformational changes. The conformational change in the thermosensitive element allows for expression or regulation of a target molecule 113. In some embodiments, the conformational change obstructs or de-obstructs a regulatory element. In some embodiments, the regulatory element is a genetic regulatory element. In some embodiments, the regulatory element is configured to express and / or regulate a target molecule.

[0092] In some embodiments, altered expression and / or regulation of a target molecules activates and / or deactivates one or more molecular processes. In someembodiments, the molecular process comprises a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof. In some embodiments, the conformational change is irreversible. In some embodiments, the conformational change is reversible. In some embodiments, continued application of the signal results in a second conformational change. In some embodiments, continued application of the signal results in a plurality of conformational changes. In some embodiments, continued application of the signal results in 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes, or a number of conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, continued application of the signal results in between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7, and 7 to 10 conformational changes. In some embodiments, application of a second signal results in a second conformational change. In some embodiments, application of a second signal results in a plurality of conformational changes. In some embodiments, application of a second signal results in 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes, or a number of conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, application of a second signal results in between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7, and 7 to 10 conformational changes. In some embodiments, cessation of the signal reverts the thermosensitive element to the first conformation. In some embodiments, application of the second signal reverts the thermosensitive element to the first conformation. In some embodiments, application of the second signal reverts the thermosensitive element to the first conformation.

[0093] In some embodiments, transduction 109 of the signal 107 to the thermosensitive element 101 increases the temperature of the thermosensitive element 101. In some embodiments, transduction 109 of the signal 107 to the thermosensitive element 101 increases the free energy of the thermosensitive element. In some embodiments, the temperature or free energy (AG) of the thermosensitive element 101 decreases following cessation of the signal. In some embodiments, the conformational change 111 obstructs or deobstructs one or more genetic elements 113. In some embodiments, the conformational change obstructs one or more genetic elements. In some embodiments, the conformational change de-obstructs one or more genetic elements. In some embodiments, the conformational change sterically hinders one or more genetic elements. In some embodiments, the conformational change relieves one or more sterically hindered genetic elements. In some embodiments, the thermosensitive element comprises the target molecule. In some embodiments, the target molecule is extraneous to the construct. In some embodiments, the target molecule is a naturally occurring molecule. In some embodiments, the target molecule is a synthetic or artificial molecule.

[0094] Some embodiments herein are directed to a construct for programmed conformational change. By way of example, FIG. 2 is an illustration depicting some embodiments of a construct 200 for programmed conformational change. In some embodiments, a construct 200 for conformational change is disclosed. In some embodiments, the construct comprises a thermosensitive element 201, and a signal transducing element 203. In some embodiments, the thermosensitive element 201 is a thermosensitive nucleic acid. In some embodiments, the thermosensitive element 201 is attached to the signal transducing element 203 by a linker.

[0095] In some embodiments, the construct comprises a plurality of thermosensitive elements. In some embodiments, each thermosensitive element is identical. In some embodiments, one or more different thermosensitive elements are attached to the signal transducing element 203. In some embodiments, the signal transducing element 203 and the thermosensitive element 201 are chosen for their ability to transduce and receive a signal of a desired type. In some embodiments, the signal transducing element 203 and the thermosensitive element 201 are chosen for their ability to transduce and receive a signal 205 comprising a desired characteristic, such as a specific signal strength or frequency. In some embodiments, the thermosensitive element is a molecular thermometer. In some embodiments, the thermosensitive element is a nucleic acid. In some embodiments, the thermosensitive element is a nucleic acid thermometer. In some embodiments, the thermosensitive element is a protein. In some embodiments the thermosensitive element comprises one or more genetic elements. In some embodiments, the one or more genetic elements are genetic regulatory elements. In some embodiments, the one or more genetic elements are sterically hindered. In some embodiments, the thermosensitive element comprises an RNA binding protein. In some embodiments, the thermosensitive element comprises one or more stem-loop binding proteins.In some embodiments, the thermosensitive element comprises one or more MS2 coat proteins and / or MS2 stem loops. In some embodiments, the thermosensitive element is a protein. In some embodiments the thermosensitive element comprises one or more genetic elements. In some embodiments, the one or more genetic elements are genetic regulatory elements. In some embodiments, the one or more genetic elements are sterically hindered. In some embodiments, the thermosensitive element comprises a first confirmation. In some embodiments, the thermosensitive element comprises a plurality of conformations 213.

[0096] In some embodiments, the signal transducing element 203 comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element 203 comprises ferritin. In some embodiments, the signal transducing element 203 comprises a ferritin nanoparticle. In some embodiments, the signal transducing element 203 comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an iron oxide nanoparticle.

[0097] A signal 205 applied to the signal transducing element is transduced 207 to the thermosensitive element in a nascent, or starting, Conformation A 209. In some embodiments, the signal is a wireless signal. In some embodiments, the signal is a tissue penetrating signal. In some embodiments, the signal is an electromagnetic signal. In some embodiments, the type of signal is chosen for its suitability for transduction between the signal transducing element and the thermosensitive element. In some embodiments, the strength of the signal is chosen for its ability to induce a desired conformational change upon transduction of the signal from the signal transducing particle to the thermosensitive particle. In some embodiments, the signal is applied intermittently. Transduction of the signal 205 to the thermosensitive element 201 causes a conformational change 211 in the thermosensitive element, with the thermosensitive element 201 going from Conformation A 209 to Conformation B 211. Continued application of the same signal or a different signal may result in further conformational changes 213. In some embodiments, continued application of the signal results in 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes, or a number of conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, continued application of the signal results in between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7,and 7 to 10 conformational changes. In some embodiments, application of a second signal results in a second conformational change. In some embodiments, application of a second signal results in a plurality of conformational changes. In some embodiments, application of a second signal results in 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes, or a number of conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, application of a second signal results in between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7, and 7 to 10 conformational changes. In some embodiments, the conformational changes are irreversible. In some embodiments, the conformational changes are reversible. In some embodiments, cessation of the signal or application of a different signal reverts the thermosensitive element to the nascent configuration 215 or to an intermediate configuration 217. In some embodiments, application of the second signal reverts the thermosensitive element to the first conformation. In some embodiments, the conformational change in the thermosensitive element allows for expression or regulation of a target molecule. In some embodiments, the conformational change obstructs or de-obstructs a regulatory element. In some embodiments, the regulatory element is a genetic regulatory element. In some embodiments, the regulatory element is configured to express and / or regulate a target molecule.

[0098] In some embodiments, altered expression and / or regulation of a target molecules activates and / or deactivates one or more molecular processes. In some embodiments, the molecular process comprises a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof. In some embodiments, transduction of the signal to the thermosensitive element increases the temperature of the thermosensitive element. In some embodiments, transduction of the signal to the thermosensitive element increases the free energy of the thermosensitive element. In some embodiments, the temperature or free energy (AG) of the thermosensitive element decreases following cessation of the signal. In some embodiments, the conformational change obstructs or de-obstructs one or more genetic elements. In some embodiments, the conformational change sterically hinders one or more genetic elements. In some embodiments, the conformational change relieves one or moresterically hindered genetic elements. In some embodiments, the thermosensitive element comprises the target molecule. In some embodiments, the target molecule is extraneous to the construct. In some embodiments, the target molecule is a naturally occurring molecule. In some embodiments, the target molecule is a synthetic or artificial molecule.

[0099] Some embodiments herein are directed to a gene expression construct. For example, FIG. 3 is an illustration depicting some embodiments of a gene expression construct 300. In some embodiments, a gene expression construct 300 is disclosed. In some embodiments, the gene expression construct 300 comprises a thermosensitive nucleic acid 301 , for example, but not limited to an RNA thermometer, and a magnetically-susceptible nanoparticle 303, for example, but not limited to, a PolyG-functionalized MNP. In some embodiments, the thermosensitive nucleic acid is attached to the magnetically-susceptible nanoparticle by a linker 304, for example but not limited to, a GA linker.

[0100] In some embodiments, the gene expression construct 300 comprises multiple thermosensitive nucleic acids. In some embodiments, each thermosensitive nucleic acid is identical. In some embodiments, one or more different thermosensitive nucleic acids are attached to the magnetically-susceptible nanoparticle. In some embodiments, the magnetically-susceptible nanoparticle and the thermosensitive nucleic acid are chosen for their ability to transduce and receive a signal of a desired type. In some embodiments, the magnetically-susceptible nanoparticle and the thermosensitive nucleic acid are chosen for their ability to transduce and receive a signal comprising a desired characteristic, such as a specific signal strength or frequency. In some embodiments, the thermosensitive nucleic acid 301 is a molecular thermometer. In some embodiments, the thermosensitive nucleic acid 301 is a nucleic acid thermometer. In some embodiments the thermosensitive nucleic acid 301 comprises one or more genetic elements 305, for example, but not limited to, Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / orany combination thereof. In some embodiments, the thermosensitive element comprises an RNA binding protein. In some embodiments, the thermosensitive element comprises one or more stem-loop binding proteins. In some embodiments, the thermosensitive element comprises one or more MS2 coat proteins and / or MS2 stem loops. In some embodiments, the one or more genetic elements 305 are genetic regulatory elements. In some embodiments, the one or more genetic elements 305 are sterically hindered.

[0101] In some embodiments, the signal transducing element 303 comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element 303 comprises ferritin. In some embodiments, the signal transducing element 303 comprises a ferritin nanoparticle. In some embodiments, the signal transducing element 303 comprises an oxidized nanoparticle. In some embodiments, the oxidized nanoparticle is an iron oxide nanoparticle.

[0102] A signal 307 applied to the magnetically-susceptible nanoparticle 303 is transduced 309 to the thermosensitive nucleic acid 301. In some embodiments, the signal 307 is a wireless signal. In some embodiments, the signal 307 is a tissue penetrating signal. In some embodiments, the signal 307 is an electromagnetic signal. In some embodiments, the type of signal is chosen for its suitability for transduction between the magnetically-susceptible nanoparticle and the thermosensitive nucleic acid. In some embodiments, the strength of the signal is chosen for its ability to induce a desired conformational change upon transduction of the signal from the magnetically-susceptible nanoparticle to the thermosensitive nucleic acid. In some embodiments, the signal 307 is applied intermittently. Transduction 309 of the signal 307 to the thermosensitive nucleic acid 301 causes a conformational change 311 in the thermosensitive element 301, with the conformational change 311 in the thermosensitive nucleic acid 301 allowing for expression or regulation of a target molecule 313, for example, but not limited to, mRNA. In some embodiments, the conformational change obstructs or deobstructs a regulatory element. In some embodiments, the regulatory element is a genetic regulatory element. In some embodiments, the regulatory element is configured to express and / or regulate a target molecule.

[0103] In some embodiments, altered expression and / or regulation of a target molecules activates and / or deactivates one or more molecular processes. In someembodiments, the molecular process comprises a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof. In some embodiments, the conformational change is irreversible. In some embodiments, the conformational change is reversible. In some embodiments, continued application of the signal or of a different signal results in one or more further conformational changes. In some embodiments, continued application of the signal results in 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes, or a number of conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, continued application of the signal results in between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7, and 7 to 10 conformational changes. In some embodiments, application of a second signal results in a second conformational change. In some embodiments, application of a second signal results in a plurality of conformational changes. In some embodiments, application of a second signal results in 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes, or a number of conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, application of a second signal results in between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7, and 7 to 10 conformational changes. In some embodiments, cessation of the signal or application of a different signal reverts the thermosensitive element to a nascent or intermediate conformation. In some embodiments, application of the second signal reverts the thermosensitive element to the first conformation.

[0104] In some embodiments, transduction 309 of the signal 307 to the thermosensitive nucleic acid increases 301 the temperature of the thermosensitive element. In some embodiments, transduction 309 of the signal 307 to the thermosensitive nucleic acid 301 increases the free energy of the thermosensitive nucleic acid. In some embodiments, the temperature or free energy (AG) of the thermosensitive nucleic acid 301 decreases following cessation of the signal 307. In some embodiments, the conformational change obstructs or deobstructs one or more genetic elements. In some embodiments, the conformational change sterically hinders one or more genetic elements. In some embodiments, the conformational change relieves one or more sterically hindered genetic elements. In some embodiments, thethermosensitive nucleic acid comprises the target molecule. In some embodiments, the target molecule is extraneous to the construct. In some embodiments, the target molecule is a naturally occurring molecule. In some embodiments, the target molecule is a synthetic or artificial molecule.

[0105] FIG. 6 is an illustration depicting a construct including a ferritin-RNA- Binding protein (RBP), according to some embodiments. In some embodiments, the construct 600 comprises a thermosensitive element 603, for example, but not limited to RNA or DNA , and a signal transducing element 601, for example, but not limited to, ferritin. In some embodiments, the thermosensitive element is attached to the ferritin by a linker 605. In some embodiments, the linker comprises a RBP 607. In some embodiments, the thermosensitive element comprises a RBP. In some embodiments, the RBP binds RNA at one or more RBP binding sites 609.

[0106] FIG. 7 is an illustration depicting a construct including a ferritin-stem-loop- binding-protein (SLBP) fusion peptide, according to some embodiments. In some embodiments, the construct 700 comprises a thermosensitive element 701, for example, but not limited to RNA or DNA, and a signal transducing element 703, for example, but not limited to, ferritin. In some embodiments, the thermosensitive element is attached to the ferritin by a linker 705. In some embodiments, the linker comprises a stem-loop binding protein 707. In some embodiments, the thermosensitive element comprises a stem-loop binding protein.

[0107] FIG. 8 is an illustration depicting a construct including a ferritin-MS2 Coat Protein (MCP) fusion peptide, according to some embodiments. In some embodiments, the construct 800 comprises a thermosensitive element 801, for example, but not limited to RNA or DNA, and a signal transducing element 803, for example, but not limited to, ferritin. In some embodiments, the thermosensitive element is attached to the ferritin by a linker 805, for example, but not limited to, a GS linker. In some embodiments, the linker is a RBP, for example MS2 Coat Protein (MCP) 807. In some embodiments, the thermosensitive element comprises a RBP, for example MS2 Coat Protein (MCP).

[0108] In some embodiments, the construct comprises more than one thermosensitive element. In some embodiments, the construct comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, or 50, thermosensitive elements, or a number of thermosensitive elements that is in a range defined by any two of the preceding values. For example, in someembodiments, the construct comprises between 1 to 50 thermosensitive elements, 1 to 40 thermosensitive elements, 1 to 30 thermosensitive elements, 1 to 25 thermosensitive elements, 1 to 20 thermosensitive elements, 1 to 10 thermosensitive elements, 1 to 7 thermosensitive elements, 1 to 5 thermosensitive elements, 1 to 3 thermosensitive elements, 3 to 50 thermosensitive elements, 3 to 40 thermosensitive elements, 3 to 30 thermosensitive elements, 3 to 25 thermosensitive elements, 3 to 20 thermosensitive elements, 3 to 10 thermosensitive elements, 3 to 7 thermosensitive elements, 3 to 5 thermosensitive elements, 5 to 50 thermosensitive elements, 5 to 40 thermosensitive elements, 5 to 30 thermosensitive elements, 5 to 25 thermosensitive elements, 5 to 20 thermosensitive elements, 5 to 10 thermosensitive elements, 5 to 7 thermosensitive elements, 7 to 50 thermosensitive elements, 7 to 40 thermosensitive elements, 7 to 30 thermosensitive elements, 7 to 25 thermosensitive elements, 7 to 20 thermosensitive elements, 7 to 10 thermosensitive elements, 10 to 50 thermosensitive elements, 10 to 40 thermosensitive elements, 10 to 30 thermosensitive elements, 10 to 25 thermosensitive elements, 10 to 20 thermosensitive elements, 20 to 50 thermosensitive elements, 20 to 40 thermosensitive elements, 20 to 30 thermosensitive elements, 20 to 25 thermosensitive elements, 25 to 50 thermosensitive elements, 25 to 40 thermosensitive elements, 30 to 50 thermosensitive elements, 30 to 40 thermosensitive elements, or 40 to 50 thermosensitive elements. In some embodiments, the construct comprises more than 50 thermosensitive elements. In some embodiments the thermosensitive element comprises a nucleic acid. In some embodiments, the nucleic acid is RNA or DNA. In some embodiments, the thermosensitive element comprises a molecular thermometer. In some embodiments, the molecular thermometer is a nucleic acid thermometer. RNA or DNA thermometer. In some embodiments, the thermosensitive element comprises a protein. In some embodiments, the thermosensitive element is a polynucleotide. In some embodiments, the thermosensitive element comprises an oligonucleotide. In some embodiments, the thermosensitive element is naturally derived. In some embodiments, the thermosensitive element is synthetic or artificial. In some embodiments, the thermosensitive element comprises an aptamer.

[0109] In some embodiments, the thermosensitive element comprises one or more genetic elements. In some embodiments, the thermosensitive element comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, genetic elements, or a number of genetic elements that is in a range defined by any two of the preceding values. For example, in some embodiments, the thermosensitiveelement comprises between 1-10, 1-7, 1-5, 1-3, 1-2, 2-10, 2-7, 2-5, 2-3, 3-10, 3-7, 3-5, 5-10, 5-7, or 7-10, genetic elements. In some embodiments, the thermosensitive element comprises more than 10 genetic elements. In some embodiments, the one or more genetic elements comprise prokaryotic genetic elements. In some embodiments, the one or more genetic elements comprise eukaryotic elements. In some embodiments, the one or more genetic elements comprise one or more promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, catalytic RNAs (e.g., ribozymes, Self-splicing RNA), intron splice sites, restriction cleavage sites, single guide RNA (sgRNA), and / or any combination thereof. Other genetic elements are known in the art. In some embodiments, the genetic element comprises any suitable genetic element. For example, repositories of parts, i.e., genetic elements, can be found at Synthetic Biology Open Language (SBOL) resource and application database, iGEM Parts Registry, iGEM-based database of available biobricks, and SynBioHub Larger BioBrick database, each of which are hereby incorporated by reference in their entirety for all purposes. In some embodiments, the genetic element comprises one or more suitable genetic elements in the SBOL resource and application database, iGEM Parts Registry, iGEM- based database of available biobricks, and SynBioHub Larger BioBrick database, or any combination thereof. In some embodiments, the thermosensitive element comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof, that is in a range defined by any two of the preceding values. For example, in some embodiments, the thermosensitive element comprises between 1-10, 1-7, 1-5, 1-3, 1-2, 2-10, 2-7, 2-5, 2-3, 3-10,3-7, 3-5, 5-10, 5-7, or 7-10, Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0110] In some embodiments, one or more of the genetic elements are sterically hindered. In some embodiments, the one or more genetic elements comprise a sterically- hindered promoter, enhancer, repressor, silencer, and / or insulator. In some embodiments, the one or more genetic elements comprise a sterically-hindered ribosome binding site, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly-A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancer (CITEs), sterically hindered transcription factor binding site, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding site, sterically hindered Shine-Dalgarno sequence, sterically hindered Kozak sequence, and / or any combination thereof. In some embodiments, the thermosensitive element comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, sterically hindered promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, sterically hindered 5' caps, ribosomal translation start codons, sterically hindered 3' termini, sterically hindered 3' poly-A tails, sterically hindered internal ribosomal entry sites (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, sterically hindered Shine-Dalgarno sequences, sterically hindered Kozak sequences, and / or any combination thereof, or a number of sterically hindered promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, sterically hindered 5' caps, ribosomal translation start codons, sterically hindered 3' termini, sterically hindered 3' poly-A tails, sterically hindered internal ribosomal entry sites (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hinderedtranslation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, sterically hindered Shine-Dalgarno sequences, and / or sterically hindered Kozak sequences, that is in a range defined by any two of the preceding values. For example, in some embodiments, the thermosensitive element comprises between 1-10, 1-7, 1-5, 1-3, 1- 2, 2-10, 2-7, 2-5, 2-3, 3-10, 3-7, 3-5, 5-10, 5-7, or 7-10, sterically hindered promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, sterically hindered 5' caps, ribosomal translation start codons, sterically hindered 3' termini, sterically hindered 3' poly- A tails, sterically hindered internal ribosomal entry sites (IRES), sterically hindered capindependent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, sterically hindered Shine-Dalgarno sequences, and / or sterically hindered Kozak sequences.

[0111] In some embodiments, the signal transducing element is attached to the thermosensitive element by a linker. The linker may be any linker suitable for attaching the signal transducing element and the thermosensitive element. In some embodiments the linker connects to one or both of the signal transducing element and thermosensitive element by a covalent or non-covalent bond. In some embodiments, the linker is chosen for its suitability in providing a chemical or mechanical property to the construct, such as hydrophobicity, hydrophilicity, electrical charge, polarity, rigidity, or flexibility. In some embodiments, the linker comprises two or more functional groups that facilitate coupling of the linker to the signal transducing element and the thermosensitive element. In some embodiments, the linker may include a polyfunctional linker such as a homobifunctional linker, heterobifunctional linker, homopolyfunctional linker, or heteropolyfunctional linker. Exemplary compositions for linkers can include, but are not limited to, a polyethylene glycol (PEG), polyethylene oxide (PEO), amino acid, polypeptide, nucleotide, nucleic acid, nucleic acid origami, dendrimer, protein nucleic acid (PNA), polysaccharide, carbon, nitrogen, oxygen, ether, sulfur, or disulfide. In some embodiments, the linker is a bead or particle such as a structured nucleic acid particle.

[0112] The signal transducing element may comprise any particle suitable for transduction of a signal applied to the signal transducing element to the thermosensitive element. In some embodiments, the signal transducing element is chosen for its ability totransduce a signal of a desired type, for example an electromagnetic signal. In some embodiments, the signal transducing element comprises a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In some embodiments, the signal transducing element comprises an organic nanoparticle. In some embodiments, the organic nanoparticle comprises a dendrimer, liposome, micelle, and / or a protein complex, for example ferritin. In some embodiments, the signal transducing element comprises a carbon-based nanoparticle. In some embodiments, the carbon-based nanoparticle comprises a fullerene, carbon black nanoparticle, quantum dot, nanodiamond, and / or carbon nano onion. In some embodiments, the signal transducing element comprises an inorganic nanoparticle. In some embodiments, the inorganic nanoparticle comprises a metallic, monometallic, bimetallic, polymetallic, alloy based, ceramic, semiconductor, carbonate, carbide, phosphate, and / or a metal oxide-based nanoparticle. In some embodiments, the signal transducing element comprises a nanoparticle, magnetic nanoparticle, nucleic acid nanostructure, protein, protein complex, ferritin nanoparticle, oxidized nanoparticle, and / or an iron oxide nanoparticle, or any combination thereof.

[0113] In some embodiments, a signal is applied to the signal transducing construct. In some embodiments, the signal comprises a tissue penetrating signal. In some embodiments, the signal comprises a wireless signal. In some embodiments, the signal comprises an optical signal. In some embodiments, the signal comprises a chemical signal. In some embodiments, the signal comprises an electrical signal. In some embodiments, the signal comprises a magnetic signal. In some embodiments, the signal comprises an electromagnetic signal. In some embodiments, the signal comprises an alternating magnetic field. In some embodiments, the signal comprises magnetic field gradients. In some embodiments, the signal comprises a combination of signals. In some embodiments, the signal is chosen for its suitability to be transduced between a desired signal transducing element and a thermosensitive element.

[0114] In some embodiments, the signal comprises a magnetic field. In some embodiments, the magnetic field has a frequency of about 0.1 MHz, about 0.2 MHz, about 0.3 MHz, about 0.4 MHz, about 0.5 MHz, about 0.6 MHz, about 0.7 MHz, about 0.8 MHz, about 0.9 MHz, about 1 MHz, about 2 MHz, about 3 MHz, about 4 MHz, about 5 MHz, about 6 MHz, about 7 MHz, about 8 MHz, about 9 MHz, about 10 MHz, about 11 MHz, about 12MHz, about 13 MHz, about 14 MHz, about 15 MHz, about 16 MHz, about 17 MHz, about 18MHz, about 19 MHz, about 20 MHz, about 25 MHz, about 30 MHz, about 35 MHz, about 40MHz, about 45 MHz, about 50 MHz, about 70 MHz, about 70 MHz, about 75 MHz, about 80MHz, about 90 MHz, about 100 MHz, about 110 MHz, about 120 MHz, about 130 MHz, about 140 MHz, about 150 MHz, about 160 MHz, about 170 MHz, about 175 MHz, about 180 MHz, about 185 MHz, about 190 MHz, about 200 MHz, about 210 MHz, about 220 MHz, about 230 MHz, about 240 MHz, about 250 MHz, about 300 MHz, about 400 MHz, about 500 MHz, about 600 MHz, about 700 MHz, about 750 MHz, about 800 MHz, about 900 MHz, or about 1,000 MHz, or at a frequency that is in a range defined by any two of the preceding values. For example, in some embodiments, the magnetic field has a frequency of between about 0.1 MHz to about 1000 MHz, about 0.1 MHz to about 750 MHz, about 0.1 MHz to about 500 MHz, about 0.1 MHz to about 250 MHz, about 0.1 MHz to about 100 MHz, about 0.1 MHz to about 75 MHz, about 0.1 MHz to about 50 MHz, about 0.1 MHz to about 25 MHz, about 0.1 MHz to about 10 MHz, about 0.1 MHz to about 1 MHz, about 0.1 MHz to about 0.5 MHz, about 0.5 MHz to about 1000 MHz, about 0.5 MHz to about 750 MHz, about 0.5 MHz to about 500 MHz, about 0.5 MHz to about 250 MHz, about 0.5 MHz to about 100 MHz, about 0.5 MHz to about 75 MHz, about 0.5 MHz to about 50 MHz, about 0.5 MHz to about 25 MHz, about 0.5 MHz to about 10 MHz, about 0.5 MHz to about 5 MHz, about 0.5 MHz to about 1 MHz, about 1 MHz to about 1000 MHz, about 1 MHz to about 750 MHz, about 1 MHz to about 500 MHz, about 1 MHz to about 250 MHz, about 1 MHz to about 100 MHz, about 1 MHz to about 75 MHz, about 1 MHz to about 50 MHz, about 1 MHz to about 25 MHz, about 1 MHz to about 10 MHz, about 10 MHz to about 1000 MHz, about 10 MHz to about 750 MHz, about 10 MHz to about 500 MHz, about 10 MHz to about 250 MHz, about 10 MHz to about 100 MHz, about 10 MHz to about 75 MHz, about 10 MHz to about 50 MHz, about 10 MHz to about 25 MHz, about 25 MHz to about 1000 MHz, about 25 MHz to about 750 MHz, about 25 MHz to about 500 MHz, about 25 MHz to about 250 MHz, about 25 MHz to about 100 MHz, about 25 MHz to about 75 MHz, about 25 MHz to about 50 MHz, about 50 MHz to about 1000 MHz, about 50 MHz to about 750 MHz, about 50 MHz to about 500 MHz, about 50 MHz to about 250 MHz, about 50 MHz to about 100 MHz, about 50 MHz to about 75 MHz, about 75 MHz to about 1000 MHz, about 75 MHz to about 750 MHz, about 75 MHz to about 500 MHz, about 75 MHz to about 250 MHz, about 75 MHz to about 100 MHz, about 100 MHz to about 1000MHz, about 100 MHz to about 750 MHz, about 100 MHz to about 500 MHz, 100 MHz to about 250 MHz, about 250 MHz to about 1000 MHz, about 250 MHz to about 750 MHz, about 250 MHz to about 500 MHz, 500 MHz to about 1000 MHz, about 500 MHz to about 750 MHz, or about 750 MHz to about 1000 MHz.

[0115] In some embodiments, the magnetic field comprises a field strength of about 0.1 kA / m, about 1 kA / m, about 2 kA / m, about 3 kA / m, about 4 kA / m, about 5 kA / m, about 6 kA / m, about 7 kA / m, about 8 kA / m, about 9 kA / m, about 10 kA / m, about 11 kA / m, about 12 kA / m, about 13 kA / m, about 14 kA / m, about 15 kA / m, about 16 kA / m, about 17 kA / m, about 18 kA / m, about 19 kA / m, about 20 kA / m, about 25 kA / m, about 30 kA / m, about 35 kA / m, about 40 kA / m, about 45 kA / m, about 50 kA / m, about 55 kA / m, about 60 kA / m, about 65 kA / m, about 70 kA / m, about 75 kA / m, about 80 kA / m, about 85 kA / m, about 90 kA / m, about 95 kA / m, or about 100 kA / m, or at a field strength that is in a range defined by any two of the preceding values. For example, in some embodiments, the magnetic field comprises a field strength of between about 0.1 kA / m to about 100 kA / m, about 0.1 kA / m to about 75 kA / m, about 0.1 kA / m to about 50 kA / m, about 0.1 kA / m to about 25 kA / m, about 0.1 kA / m to about 20 kA / m, about 0.1 kA / m to about 10 kA / m, about 0.1 kA / m to about 5 kA / m, about 0.1 kA / m to about 1 kA / m, about 1 kA / m to about 100 kA / m, about 1 kA / m to about 75 kA / m, about 1 kA / m to about 50 kA / m, about 1 kA / m to about 25 kA / m, about 1 kA / m to about 20 kA / m, about 1 kA / m to about 10 kA / m, about 1 kA / m to about 5 kA / m, about 5 kA / m to about 100 kA / m, about 5 kA / m to about 75 kA / m, about 5 kA / m to about 50 kA / m, about 5 kA / m to about 25 kA / m, about 5 kA / m to about 20 kA / m, about 5 kA / m to about 10 kA / m, about 10 kA / m to about 100 kA / m, about 10 kA / m to about 75 kA / m, about 10 kA / m to about 50 kA / m, about 10 kA / m to about 25 kA / m, about 10 kA / m to about 20 kA / m, about 20 kA / m to about 100 kA / m, about 20 kA / m to about 75 kA / m, about 20 kA / m to about 50 kA / m, about 20 kA / m to about 25 kA / m, about 25 kA / m to about 100 kA / m, about 25 kA / m to about 75 kA / m, about 25 kA / m to about 50 kA / m, about 50 kA / m to about 100 kA / m, about 50 kA / m to about 75 kA / m, or about 75 kA / m to about 100 kA / m.

[0116] In some embodiments, the magnetic field is an alternating magnetic field. In some embodiments, the alternating magnetic field has a frequency of about 0.1 MHz, about 0.2 MHz, about 0.3 MHz, about 0.4 MHz, about 0.5 MHz, about 0.6 MHz, about 0.7 MHz, about 0.8 MHz, about 0.9 MHz, about 1 MHz, about 2 MHz, about 3 MHz, about 4 MHz,about 5 MHz, about 6 MHz, about 7 MHz, about 8 MHz, about 9 MHz, about 10 MHz, about 15 MHz, about 20 MHz, about 25 MHz, about 30 MHz, about 35 MHz, about 40 MHz, about 45 MHz, about 50 MHz, about 60 MHz, about 70 MHz, about 75 MHz, about 80 MHz, about 90 MHz, about 100 MHz, about 150 MHz, about 200 MHz, about 250 MHz, about 300 MHz, about 400 MHz, about 500 MHz, about 600 MHz, about 700 MHz, about 750 MHz, about 800 MHz, about 900 MHz, or about 1000 MHz, or at a frequency that is in a range defined by any two of the preceding values. For example, in some embodiments, the alternating magnetic field has a frequency of between about 0.1 MHz to about 1000 MHz, about 0.1 MHz to about 750 MHz, about 0.1 MHz to about 500 MHz, about 0.1 MHz to about 250 MHz, about 0.1 MHz to about 100 MHz, about 0.1 MHz to about 75 MHz, about 0.1 MHz to about 50 MHz, about 0.1 MHz to about 25 MHz, about 0.1 MHz to about 10 MHz, about 0.1 MHz to about 1 MHz, about 0.1 MHz to about 0.5 MHz, about 0.5 MHz to about 1000 MHz, about 0.5 MHz to about 750 MHz, about 0.5 MHz to about 500 MHz, about 0.5 MHz to about 250 MHz, about 0.5 MHz to about 100 MHz, about 0.5 MHz to about 75 MHz, about 0.5 MHz to about 50 MHz, about 0.5 MHz to about 25 MHz, about 0.5 MHz to about 10 MHz, about 0.5 MHz to about 5 MHz, about 0.5 MHz to about 1 MHz, about 1 MHz to about 1000 MHz, about 1 MHz to about 750 MHz, about 1 MHz to about 500 MHz, about 1 MHz to about 250 MHz, about 1 MHz to about 100 MHz, about 1 MHz to about 75 MHz, about 1 MHz to about 50 MHz, about 1 MHz to about 25 MHz, about 1 MHz to about 10 MHz, about 10 MHz to about 1000 MHz, about 10 MHz to about 750 MHz, about 10 MHz to about 500 MHz, about 10 MHz to about 250 MHz, about 10 MHz to about 100 MHz, about 10 MHz to about 75 MHz, about 10 MHz to about 50 MHz, about 10 MHz to about 25 MHz, about 25 MHz to about 1000 MHz, about 25 MHz to about 750 MHz, about 25 MHz to about 500 MHz, about 25 MHz to about 250 MHz, about 25 MHz to about 100 MHz, about 25 MHz to about 75 MHz, about 25 MHz to about 50 MHz, about 50 MHz to about 1000 MHz, about 50 MHz to about 750 MHz, about 50 MHz to about 500 MHz, about 50 MHz to about 250 MHz, about 50 MHz to about 100 MHz, about 50 MHz to about 75 MHz, about 75 MHz to about 1000 MHz, about 75 MHz to about 750 MHz, about 75 MHz to about 500 MHz, about 75 MHz to about 250 MHz, about 75 MHz to about 100 MHz, about 100 MHz to about 1000 MHz, about 100-750 MHz, about 100-500 MHz, about 100-250 MHz, about 250-1000 MHz, about 250-750 MHz, about 250-500 MHz, about 500-1000 MHz, about 500-750 MHz, or about 750 MHz to about 1000 MHz.

[0117] In some embodiments, the alternating magnetic field comprises a field strength of about 0.1 kA / m, about 1 kA / m, about 2 kA / m, about 3 kA / m, about 4 kA / m, about 5 kA / m, about 6 kA / m, about 7 kA / m, about 8 kA / m, about 9 kA / m, about 10 kA / m, about 11 kA / m, about 12 kA / m, about 13 kA / m, about 14 kA / m, about 15 kA / m, about 16 kA / m, about 17 kA / m, about 18 kA / m, about 19 kA / m, about 20 kA / m, about 25 kA / m, about 30 kA / m, about 35 kA / m, about 40 kA / m, about 45 kA / m, about 50 kA / m, about 55 kA / m, about 60 kA / m, about 65 kA / m, about 70 kA / m, about 75 kA / m, about 80 kA / m, about 85 kA / m, about 90 kA / m, about 95 kA / m, or about 100 kA / m, or at a field strength that is in a range defined by any two of the preceding values. For example, in some embodiments, the alternating magnetic field comprises a field strength of between about 0.1 kA / m to about 100 kA / m, about 0.1 kA / m to about 75 kA / m, about 0.1 kA / m to about 50 kA / m, about 0.1 kA / m to about 25 kA / m, about 0.1 kA / m to about 20 kA / m, about 0.1 kA / m to about 10 kA / m, about 0.1 kA / m to about 5 kA / m, about 0.1 kA / m to about 1 kA / m, about 1 kA / m to about 100 kA / m, about 1 kA / m to about 75 kA / m, about 1 kA / m to about 50 kA / m, about 1 kA / m to about 25 kA / m, about 1 kA / m to about 20 kA / m, about 1 kA / m to about 10 kA / m, about 1 kA / m to about 5 kA / m, about 5 kA / m to about 100 kA / m, about 5 kA / m to about 75 kA / m, about 5 kA / m to about 50 kA / m, about 5 kA / m to about 25 kA / m, about 5 kA / m to about 20 kA / m, about 5 kA / m to about 10 kA / m, about 10 kA / m to about 100 kA / m, about 10 kA / m to about 75 kA / m, about 10 kA / m to about 50 kA / m, about 10 kA / m to about 25 kA / m, about 10 kA / m to about 20 kA / m, about 20 kA / m to about 100 kA / m, about 20 kA / m to about 75 kA / m, about 20 kA / m to about 50 kA / m, about 20 kA / m to about 25 kA / m, about 25 kA / m to about 100 kA / m, about 25 kA / m to about 75 kA / m, about 25 kA / m to about 50 kA / m, about 50 kA / m to about 100 kA / m, about 50 kA / m to about 75 kA / m, or about 75 kA / m to about 100 kA / m.

[0118] In some embodiments, transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element. In some embodiments, transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element. In some embodiments, the temperature of the thermosensitive element increases by about 0.1°C, about 0.5°C, about 1°C, about 2°C, about 3°C, about 4°C, about 5°C, about 6°C, about 7°C, about 8°C, about 9°C, about 10°C, about 11°C, about 12°C, about 13°C, about 14°C, about 15°C, about 16°C, about 17°C, about 18°C, about 19°C, about 20°C, about 25°C, about 30°C, about35°C, about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, about 65°C, about 70°C, about 75°C, about 80°C, about 85°C, about 90°C, about 95°C, or about 100°C, or by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the temperature of the thermosensitive element increases by between about 0.1 °C to about 100°C, about 0.1 °C to about 75°C, about 0.1 °C to about 50°C, about 0.1 °C to about 25°C, about 0.1 °C to about 20°C, about 0.1 °C to about 10°C, about 0.1 °C to about 5°C, about 0.1 °C to about 1°C, about 1°C to about 100°C, about 1°C to about 75°C, about 1°C to about 50°C, about 1 °C to about 25°C, about 1 °C to about 20°C, about 1 °C to about 10°C, about 1°C to about 5°C, about 5°C to about 100°C, about 5°C to about 75°C, about 5°C to about 50°C, about 5°C to about 25°C, about 5°C to about 20°C, about 5°C to about 10°C, about 10°C to about 100°C, about 10°C to about 75°C, about 10°C to about 50°C, about 10°C to about 25°C, about 10°C to about 20°C, about 20°C to about 100°C, about 20°C to about 75°C, about 20°C to about 50°C, about 20°C to about 25°C, about 25°C to about 100°C, about 25°C to about 75°C, about 25°C to about 50°C, about 50°C to about 100°C, about 50°C to about 75°C, or about 75°C to about 100°C, upon transduction of a signal from the signal transducing element to the thermosensitive element. In some embodiments, the signal is chosen for its suitability in causing a desired temperature change in the thermosensitive element upon transduction of the signal from the signal transducing element to the thermosensitive element. In some embodiments, the signal is applied at a specific strength and / or duration suitable to achieve a desired temperature increase in the thermosensitive element. In some embodiments, the desired temperature change in the thermosensitive element is chosen to induce a desired conformational change in the thermosensitive element. In some embodiments, the temperature or free energy (AG) of the thermosensitive element decreases following cessation of the signal.

[0119] In some embodiments, transduction of the signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element. In some embodiments, the free energy increases by about 0.01 Kcal / mol, about 0.05 Kcal / mol, about 0.1 Kcal / mol, about 0.5 Kcal / mol, about 0.9 Kcal / mol, about 1 Kcal / mol, about 2 Kcal / mol, about 3 Kcal / mol, about 4 Kcal / mol, about 5 Kcal / mol, about 6 Kcal / mol, about 7 Kcal / mol, about 8 Kcal / mol, about 9 Kcal / mol, about 10 Kcal / mol, about 11 Kcal / mol, about 12 Kcal / mol, about 13 Kcal / mol, about 14 Kcal / mol, about 15 Kcal / mol, about 16 Kcal / mol, about 17 Kcal / mol, about 18 Kcal / mol, about 19 Kcal / mol, about 20 Kcal / mol, about 21 Kcal / mol,about 22 Kcal / mol, about 23 Kcal / mol, about 24 Kcal / mol, about 25 Kcal / mol, about 30 Kcal / mol, about 40 Kcal / mol, about 50 Kcal / mol, about 60 Kcal / mol, about 70 Kcal / mol, about 80 Kcal / mol, about 90 Kcal / mol, about 100 Kcal / mol, about 200 Kcal / mol, about 250 Kcal / mol, about 300 Kcal / mol, about 400 Kcal / mol, about 500 Kcal / mol, about 600 Kcal / mol, about 700 Kcal / mol, about 750 Kcal / mol, about 800 Kcal / mol, about 900 Kcal / mol, or about 1000 Kcal / mol, or by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, transduction of the signal to the thermosensitive element increases the free energy of the thermosensitive element by between about 0.01 Kcal / mol to about 1000 Kcal / mol, about 0.01 Kcal / mol to about 750 Kcal / mol, about 0.01 Kcal / mol to about 500 Kcal / mol, about 0.01 Kcal / mol to about 250 Kcal / mol, about 0.01 Kcal / mol to about 100 Kcal / mol, about 0.01 Kcal / mol to about 75 Kcal / mol, about 0.01 Kcal / mol to about 50 Kcal / mol, about 0.01 Kcal / mol to about 25 Kcal / mol, about 0.01 Kcal / mol to about 20 Kcal / mol, about 0.01 Kcal / mol to about 15 Kcal / mol, about 0.01 Kcal / mol to about 10 Kcal / mol, about 0.01 Kcal / mol to about 5 Kcal / mol, about 0.01 Kcal / mol to about 1 Kcal / mol, about 0.01 Kcal / mol to about 0.1 Kcal / mol, about 0.1 Kcal / mol to about 1000 Kcal / mol, about 0.1 Kcal / mol to about 750 Kcal / mol, about 0.1 Kcal / mol to about 500 Kcal / mol, about 0.1 Kcal / mol to about 250 Kcal / mol, about 0.1 Kcal / mol to about 100 Kcal / mol, about 0.1 Kcal / mol to about 75 Kcal / mol, about 0.1 Kcal / mol to about 50 Kcal / mol, about 0.1 Kcal / mol to about 25 Kcal / mol, about 0.1 Kcal / mol to about 20 Kcal / mol, about 0.1 Kcal / mol to about 15 Kcal / mol, about 0.1 Kcal / mol to about 10 Kcal / mol, about 0.1 Kcal / mol to about 5 Kcal / mol, about 0.1 Kcal / mol to about 1 Kcal / mol, about 1 Kcal / mol to about 1000 Kcal / mol, about 1 Kcal / mol to about 750 Kcal / mol, about 1 Kcal / mol to about 500 Kcal / mol, about 1 Kcal / mol to about 250 Kcal / mol, about 1 Kcal / mol to about 100 Kcal / mol, about 1 Kcal / mol to about 75 Kcal / mol, about 1 Kcal / mol to about 50 Kcal / mol, about 1 Kcal / mol to about 25 Kcal / mol, about 1 Kcal / mol to about 20 Kcal / mol, about 1 Kcal / mol to about 15 Kcal / mol, about 1 Kcal / mol to about 10 Kcal / mol, about 1 Kcal / mol to about 5 Kcal / mol, about 5 Kcal / mol to about 1000 Kcal / mol, about 5 Kcal / mol to about 750 Kcal / mol, about 5 Kcal / mol to about 500 Kcal / mol, about 5 Kcal / mol to about 250 Kcal / mol, about 5 Kcal / mol to about 100 Kcal / mol, about 5 Kcal / mol to about 75 Kcal / mol, about 5 Kcal / mol to about 50 Kcal / mol, about 5 Kcal / mol to about 25 Kcal / mol, about 5 Kcal / mol to about 20 Kcal / mol, about 5 Kcal / mol to about 15 Kcal / mol, about 5 Kcal / mol to about 10 Kcal / mol, about 10 Kcal / mol toabout 1000 Kcal / mol, about 10 Kcal / mol to about 750 Kcal / mol, about 10 Kcal / mol to about 500 Kcal / mol, about 10 Kcal / mol to about 250 Kcal / mol, about 10 Kcal / mol to about 100 Kcal / mol, about 10 Kcal / mol to about 75 Kcal / mol, about 10 Kcal / mol to about 50 Kcal / mol, about 10 Kcal / mol to about 25 Kcal / mol, about 10 Kcal / mol to about 20 Kcal / mol, about 10 Kcal / mol to about 15 Kcal / mol, about 15 Kcal / mol to about 1000 Kcal / mol, about 15 Kcal / mol to about 750 Kcal / mol, about 15 Kcal / mol to about 500 Kcal / mol, about 15 Kcal / mol to about 250 Kcal / mol, about 15 Kcal / mol to about 100 Kcal / mol, about 15 Kcal / mol to about 75 Kcal / mol, about 15 Kcal / mol to about 50 Kcal / mol, about 15 Kcal / mol to about 25 Kcal / mol, about 15 Kcal / mol to about 20 Kcal / mol, about 20 Kcal / mol to about 1000 Kcal / mol, about 20 Kcal / mol to about 750 Kcal / mol, about 20 Kcal / mol to about 500 Kcal / mol, about 20 Kcal / mol to about 250 Kcal / mol, about 20 Kcal / mol to about 100 Kcal / mol, about 20 Kcal / mol to about 75 Kcal / mol, about 20 Kcal / mol to about 50 Kcal / mol, about 20 Kcal / mol to about 25 Kcal / mol, about 25 Kcal / mol to about 1000 Kcal / mol, about 25 Kcal / mol to about 750 Kcal / mol, about 25 Kcal / mol to about 500, about 25 Kcal / mol to about 250, about 25 Kcal / mol to about 100, about 25 Kcal / mol to about 75, about 25 Kcal / mol to about 50, about 50 Kcal / mol to about 1000, about 50 Kcal / mol to about 750 Kcal / mol, about 50 Kcal / mol to about 500 Kcal / mol, about 50 Kcal / mol to about 250 Kcal / mol, about 50 Kcal / mol to about 100 Kcal / mol, about 100 Kcal / mol to about 1000 Kcal / mol, about 100 Kcal / mol to about 750 Kcal / mol, about 100 Kcal / mol to about 500 Kcal / mol, about 100 Kcal / mol to about 250 Kcal / mol, about 250 Kcal / mol to about 1000 Kcal / mol, about 250 Kcal / mol to about 750 Kcal / mol, about 250 Kcal / mol to about 500 Kcal / mol, about 500 Kcal / mol to about 1000 Kcal / mol, about 500 Kcal / mol to about 750 Kcal / mol, or about 750 Kcal / mol to about 1000 Kcal / mol. In some embodiments, the signal is applied at a specific strength and / or duration suitable to achieve a desired temperature increase in the thermosensitive element. In some embodiments, the desired change in free energy in the thermosensitive element is chosen to induce a desired conformational change in the thermosensitive element. In some embodiments, the free energy of the thermosensitive element decreases following cessation of the signal.

[0120] In some embodiments, transduction of the signal from the signal transducing element to the thermosensitive element causes a conformational change in the thermosensitive element. In some embodiments, the conformational change comprises a change in the shape or proportionate dimensions of the thermosensitive element. In someembodiments, the conformational change comprises a change in the secondary structure, tertiary structure, and / or quaternary structure of the thermosensitive element. In some embodiments, the conformational change comprises a denaturing or unwinding of the thermosensitive element. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more genetic elements on the thermosensitive element. In some embodiments, the conformational change in the thermosensitive element obstructs and / or de-obstructs one or more ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, IRES, CITEs, transcription factor binding sites, translation initiation factor (IF) binding sites, eukaryotic initiation factor (elF) binding sites, hairpin-loop structures, toehold switches, and / or any combination thereof. In some embodiments, the conformational change in the thermosensitive element sterically hinders one or more ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, IRES, CITEs, transcription factor binding sites, translation initiation factor (IF) binding sites, eukaryotic initiation factor (elF) binding sites, hairpin-loop structures, toehold switches, and / or any combination thereof. In some embodiments, the conformational change in the thermosensitive element relieves the steric hinderance from one or more sterically hindered ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, IRES, CITEs, transcription factor binding sites, translation initiation factor (IF) binding sites, eukaryotic initiation factor (elF) binding sites, hairpin-loop structures, toehold switches, and / or any combination thereof. In some embodiments, the conformational change obstructs and / or de-obstructs one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In some embodiments, the conformational change in the thermosensitive element alters expression and / or regulation of a target molecule. In some embodiments, altered expression and / or regulation of a target molecules activates and / or deactivates one or more molecular processes. In some embodiments, the molecular process comprises a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof.

[0121] In some embodiments, the conformational change in the thermosensitive element alters expression and / or regulation of a target molecule. In some embodiments, the conformational change in the thermosensitive element increases expression of a targetmolecule by about 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%; 25%; 30%; 40%; 50%; 60%; 70%; 75%; 80%; 90%; 100%; 125%; 150%; 175%; 200%; 250%; 300%; 400%; 500%; 600%; 700%; 750%; 800%; 900%; 1,000%; 2,000%; 2,500%; 3,000%; 4,000%; 5,000%; 6,000%; 7,000%; 7,500%; 8,000%; 9,000%; 10,000%; 20,000%; 25,000%; 30,000%; 40,000%; 50,000%; 60,000%; 70,000%; 75,000%; 80,000%; 85,000%; 90,000% or 100,000%; or increases expression of a target molecule by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the expression of a target molecule is increased by between about 1-100,000%; 1-75,000%; 1-50,000%; 1-25,000%; 1- 10,000%; 1-5,000%; 1-1,000%; 1-750%; 1-500%; 1-250%; 1-100%; 1-75%; 1-50%; 1-25%; 1-10%; 1-5%; 5-100,000%; 5-75,000%; 5-50,000%; 5-25,000%; 5-10,000%; 5-5,000%; 5- 1,000%; 5-750%; 5-500%; 5-250%; 5-100%; 5-75%; 5-50%; 5-25%; 5-10%; 10-100,000%; 10-75,000%; 10-50,000%; 10-25,000%; 10-10,000%; 10-5,000%; 10-1,000%; 10-750%; 10- 500%; 10-250%; 10-100%; 10-75%; 10-50%; 10-25%; 25-100,000%; 25-75,000%; 25- 50,000%; 25-25,000%; 25-10,000%; 25-5,000%; 25-1,000%; 25-750%; 25-500%; 25-250%; 25-100%; 25-75%; 25-50%; 50-100,000%; 50-75,000%; 50-50,000%; 50-25,000%; 50- 10,000%; 50-5,000%; 50-1,000%; 50-750%; 50-500%; 50-250%; 50-100%; 50-75%; 75- 100,000%; 75-75,000%; 75-50,000%; 75-25,000%; 75-10,000%; 75-5,000%; 75-1,000%; 75- 750%; 75-500%; 75-250%; 75-100%; 100-100,000%; 100-75,000%; 100-50,000%; 100- 25,000%; 100-10,000%; 100-5,000%; 100-1,000%; 100-750%; 100-500%; 100-250%; 250%- 1,000%; 250%-750%; 250%-500%; 500%-l,000%; 500%-750%; 750%-l,000%; 1,000%- 100,000%; 1,000-75,000%; 1,000-50,000%; 1,000-25,000%; 1,000-10,000%; 1,000-5,000%; 5,000-100,000%; 5,000-75,000%; 5,000-50,000%; 5,000-25,000%; 5,000-10,000%; 10,000- 100,000%; 10,000-75,000%; 10,000-50,000%; 10,000-25,000%; 25,000-100,000%; 25, GOO- 75, 000%; 25,000-50,000%; 50,000-100,000%; 50,000-75,000% or 75,000-100,000%.

[0122] In some embodiments, the conformational change in the thermosensitive element decreases expression of a target molecule by about 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%; 25%; 30%; 40%; 50%; 60%; 70%; 75%; 80%; 90%; 100%; 125%; 150%; 175%; 200%; 250%; 300%; 400%; 500%; 600%; 700%; 750%; 800%; 900%; 1,000%; 2,000%; 2,500%; 3,000%; 4,000%; 5,000%; 6,000%; 7,000%; 7,500%; 8,000%; 9,000%; 10,000%; 20,000%; 25,000%; 30,000%; 40,000%; 50,000%; 60,000%; 70,000%; 75,000%; 80,000%; 85,000%; 90,000% or 100,000%, or decreases expression of a target molecule byan amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the expression of a target molecule is decreased by between about 1-100,000%;1-75,000%; 1-50,000%; 1-25,000%; 1-10,000%; 1-5,000%; 1-1,000%; 1-750%; 1-500%; 1- 250%; 1-100%; 1-75%; 1-50%; 1-25%; 1-10%; 1-5%; 5-100,000%; 5-75,000%; 5-50,000%; 5-25,000%; 5-10,000%; 5-5,000%; 5-1,000%; 5-750%; 5-500%; 5-250%; 5-100%; 5-75%; 5- 50%; 5-25%; 5-10%; 10-100,000%; 10-75,000%; 10-50,000%; 10-25,000%; 10-10,000%; 10- 5,000%; 10-1,000%; 10-750%; 10-500%; 10-250%; 10-100%; 10-75%; 10-50%; 10-25%; 25- 100,000%; 25-75,000%; 25-50,000%; 25-25,000%; 25-10,000%; 25-5,000%; 25-1,000%; 25- 750%; 25-500%; 25-250%; 25-100%; 25-75%; 25-50%; 50-100,000%; 50-75,000%; 50- 50,000%; 50-25,000%; 50-10,000%; 50-5,000%; 50-1,000%; 50-750%; 50-500%; 50-250%; 50-100%; 50-75%; 75-100,000%; 75-75,000%; 75-50,000%; 75-25,000%; 75-10,000%; 75- 5,000%; 75-1,000%; 75-750%; 75-500%; 75-250%; 75-100%; 100-100,000%; 100-75,000%; 100-50,000%; 100-25,000%; 100-10,000%; 100-5,000%; 100-1,000%; 100-750%; 100-500%; 100-250%; 250%-l,000%; 250%-750%; 250%-500%; 500%-l,000%; 500%-750%; 750%- 1,000%; 1,000%- 100, 000%; 1,000-75,000%; 1,000-50,000%; 1,000-25,000%; 1,000- 10,000%; 1,000-5,000%; 5,000-100,000%; 5,000-75,000%; 5,000-50,000%; 5,000-25,000%; 5,000-10,000%; 10,000-100,000%; 10,000-75,000%; 10,000-50,000%; 10,000-25,000%; 25,000-100,000%; 25,000-75,000%; 25,000-50,000%; 50,000-100,000%; 50,000-75,000% or 75,000-100,000%.

[0123] In some embodiments, the conformational change in the thermosensitive element increases expression of a target molecule by about 1-fold, 2-fold, 3-fold, 4-fold, 5- fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 250-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700- fold, 750-fold, 800-fold, 900-fold or 1,000-fold, or increases expression of a target molecule by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the conformational change in the thermosensitive element increases expression of a target molecule by between about 1-fold to 1,000-fold, 1-fold to 750-fold, 1- fold to 500-fold, 1 -fold to -250-fold, 1 -fold to 100-fold, 1 -fold to 75-fold, 1 -fold to 50-fold, 1- fold to 25-fold, 1- fold to 10-fold, 1- fold to 7-fold, 1-fold to 5-fold, 1-fold to 3-fold, 1-fold to2-fold, 2-fold to 10-fold, 2-fold to 7-fold, 2-fold to 5-fold, 2-fold to 3-fold, 3-fold to 10-fold,3-fold to 7-fold, 3-fold to 5-fold, 5-fold to 1,000-fold, 5-fold to 750-fold, 5-fold to 500-fold,5-fold to -250-fold, 5-fold to 100-fold, 5-fold to 75-fold, 5-fold to 50-fold, 5-fold to 25-fold, 5-fold to 10-fold, 5-fold to 7-fold, or 7-fold to 10-fold, 10-fold to 1,000-fold, 10-fold to 750- fold, 10-fold to 500-fold, 10-fold to 250-fold, 10-fold to 100-fold, 10-fold to 75-fold, 10-fold to 50-fold, 10-fold to 25-fold, 25-fold to 1,000-fold, 25-fold to 750-fold, 25-fold to 500-fold, 25-fold to 250-fold, 25-fold to 100-fold, 25-fold to 75-fold, 25-fold to 50-fold, 50-fold to 1,000-fold, 50-fold to 750-fold, 50-fold to 500-fold, 50-fold to 250-fold, 50-fold to 100-fold, 50-fold to 75-fold, 75-fold to 1,000-fold, 75-fold to 750-fold, 75-fold to 500-fold, 75-fold to 250-fold, 75-fold to 100-fold, 100-fold to 1,000-fold, 100-fold to 750-fold, 100-fold to 500- fold, 100-fold to 250-fold, 250-fold to 1,000-fold, 250-fold to 750-fold, 250-fold to 500-fold, 500-fold to 1,000-fold, 500-fold to 750-fold, or 750-fold to 1,000-fold. In some embodiments, the conformational change in the thermosensitive element decreases expression of a target molecule by about 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 250- fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 750-fold, 800-fold, 900-fold or 1,000- fold, decreases expression of a target molecule by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the conformational change in the thermosensitive element decreases expression of a target molecule by between about 1 - fold to 1,000-fold, 1-fold to 750-fold, 1-fold to 500-fold, 1-fold to -250-fold, 1-fold to 100- fold, 1-fold to 75-fold, 1-fold to 50-fold, 1-fold to 25-fold, 1- fold to 10-fold, 1- fold to 7-fold, 1-fold to 5-fold, 1-fold to 3-fold, 1-fold to 2-fold, 2-fold to 10-fold, 2-fold to 7-fold, 2-fold to 5-fold, 2-fold to 3-fold, 3-fold to 10-fold, 3-fold to 7-fold, 3-fold to 5-fold, 5-fold to 1,000- fold, 5-fold to 750-fold, 5-fold to 500-fold, 5-fold to -250-fold, 5-fold to 100-fold, 5-fold to 75-fold, 5-fold to 50-fold, 5-fold to 25-fold, 5-fold to 10-fold, 5-fold to 7-fold, or 7-fold to 10- fold, 10-fold to 1,000-fold, 10-fold to 750-fold, 10-fold to 500-fold, 10-fold to 250-fold, 10- fold to 100-fold, 10-fold to 75-fold, 10-fold to 50-fold, 10-fold to 25-fold, 25-fold to 1,000- fold, 25-fold to 750-fold, 25-fold to 500-fold, 25-fold to 250-fold, 25-fold to 100-fold, 25-fold to 75-fold, 25-fold to 50-fold, 50-fold to 1,000-fold, 50-fold to 750-fold, 50-fold to 500-fold, 50-fold to 250-fold, 50-fold to 100-fold, 50-fold to 75-fold, 75-fold to 1,000-fold, 75-fold to 750-fold, 75-fold to 500-fold, 75-fold to 250-fold, 75-fold to 100-fold, 100-fold to 1,000-fold, 100-fold to 750-fold, 100-fold to 500-fold, 100-fold to 250-fold, 250-fold to 1,000-fold, 250-fold to 750-fold, 250-fold to 500-fold, 500-fold to 1,000-fold, 500-fold to 750-fold, or 750- fold to 1,000-fold .

[0124] In some embodiments, the construct meets the following criteria: (1) electromagnetic-based activation, (2) majority genetically-encoded architecture, (3) high spatiotemporal resolution, and (4) modular, consistent outputs. In some embodiments, the first component involves gene circuitry that encodes electromagnetic- (EM) or magnetic receptivity, processes inputs, and expresses outputs. In some embodiments, this is an RNA structure containing an nanoparticle binding domain, RNA thermometer, and output gene for expression. The nanoparticle binding domain can be one of several. In some embodiments, this consists of an MS2 bacteriophage hairpin on the RNA which adheres to a MS2 Coat Protein present on the nanoparticle. In some embodiments, the adherence may comprise Watson-Crick base pairing of a homopolymer on the 5’ end of the RNA and complementary DNA oligonucleotides adhering to the nanoparticle substrate. In some embodiments, the second component involves hardware that can accurately heat the nanoparticles via applied AMF. In some embodiments, the device must generate AMFs from 0 kHz to 1000 kHz.

[0125] In some embodiments, the construct comprises a nanoparticle-aptamer complex and an alternating-magnetic field to induce expression of a target gene of interest. In some embodiments, utilization of an AMF generator stimulates the heating of the nanoparticle core through magnetic hysteresis to unwind and translate the aptamer. In some embodiments, halting AMF results in a decrease in the temperature or free energy (AG) of the nanoparticle and stops aptamer translation. In some embodiments, coupling RNA thermometry and nanoparticle hyperthermia, improves magneto-genetic spatiotemporal control.Methods for expression or regulation of a target molecule

[0126] Some embodiments herein are directed to a method of expressing or regulating a target molecule. By way of example, FIG. 4 is a flow chart depicting some embodiments of a method of expressing or regulating a target molecule 400. In some embodiments, a method of expressing or regulating a target molecule 400 is disclosed. In some embodiments, the method comprises administering a construct for expression or regulation of a target molecule to a subject 401. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the construct comprises athermosensitive element and a signal transducing element. In some embodiments, the signal transducing element and the thermosensitive element are chosen for their ability to transduce and receive a signal of a desired type. In some embodiments, the signal transducing element and the thermosensitive element are chosen for their ability to transduce and receive a signal comprising a desired characteristic, such as a specific signal strength or frequency. In some embodiments, the method of expressing or regulating a target molecule 400 further comprises applying a signal to the signal transducing element 407. In some embodiments, the signal is applied intermittently. In some embodiments, the signal is applied continuously.

[0127] In some embodiments, application of the signal to the signal transducing element causes a conformational change in the thermosensitive element. In some embodiments, the signal is applied until 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes have occurred, or a number of conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, the signal is applied until between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7, and 7 to 10 conformational changes have occurred. In some embodiments, cessation of the signal or application of a different signal reverts the thermosensitive element to a nascent or intermediate conformation. In some embodiments, a second signal is applied to revert the thermosensitive element to the first conformation. In some embodiments, the conformational change obstructs or de-obstructs one or more genetic elements. In some embodiments, the conformational change sterically hinders one or more genetic elements. In some embodiments, the conformational change(s) in the thermosensitive element allows for expression or regulation of a target molecule.

[0128] In some embodiments, altered expression and / or regulation of a target molecules activates and / or deactivates one or more molecular processes. In some embodiments, the molecular process comprises a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof. In some embodiments, the conformational change is irreversible.

[0129] In some embodiments, the signal is applied for an amount of time sufficient to cause a desired change in the free energy of the thermosensitive element. In someembodiments, the signal is applied for an amount of time sufficient to cause a desired increase in the free energy of the thermosensitive element. In some embodiments, the signal is applied for an amount of time sufficient to cause a desired change in the temperature of the thermosensitive element. In some embodiments, the signal is applied for an amount of time sufficient to cause a desired increase in the temperature of the thermosensitive element. In some embodiments, the signal is applied for an amount of time sufficient to cause obstruction or de-obstruction of one or more genetic elements. In some embodiments, the signal is applied for an amount of time sufficient to cause steric hinderance of one or more genetic elements. In some embodiments, the signal is applied for an amount of time sufficient to allow for expression or regulation of a target molecule.

[0130] In some embodiments, the signal is applied for an amount of time sufficient to allow for an increase in the expression of a target molecule by about 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%; 25%; 30%; 40%; 50%; 60%; 70%; 75%; 80%; 90%; 100%; 125%; 150%; 175%; 200%; 250%; 300%; 400%; 500%; 600%; 700%; 750%; 800%; 900%; 1,000%; 2,000%; 2,500%; 3,000%; 4,000%; 5,000%; 6,000%; 7,000%; 7,500%; 8,000%; 9,000%; 10,000%; 20,000%; 25,000%; 30,000%; 40,000%; 50,000%; 60,000%; 70,000%; 75,000%; 80,000%; 85,000%; 90,000% or 100,000%; or increases expression of a target molecule by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, signal is applied for an amount of time sufficient to allow for an increase in the expression of a target molecule by between about 1-100,000%; 1-75,000%; 1-50,000%; 1-25,000%; 1-10,000%; 1-5,000%; 1-1,000%; 1-750%; 1-500%; 1-250%; 1- 100%; 1-75%; 1-50%; 1-25%; 1-10%; 1-5%; 5-100,000%; 5-75,000%; 5-50,000%; 5- 25,000%; 5-10,000%; 5-5,000%; 5-1,000%; 5-750%; 5-500%; 5-250%; 5-100%; 5-75%; 5- 50%; 5-25%; 5-10%; 10-100,000%; 10-75,000%; 10-50,000%; 10-25,000%; 10-10,000%; 10- 5,000%; 10-1,000%; 10-750%; 10-500%; 10-250%; 10-100%; 10-75%; 10-50%; 10-25%; 25- 100,000%; 25-75,000%; 25-50,000%; 25-25,000%; 25-10,000%; 25-5,000%; 25-1,000%; 25- 750%; 25-500%; 25-250%; 25-100%; 25-75%; 25-50%; 50-100,000%; 50-75,000%; 50- 50,000%; 50-25,000%; 50-10,000%; 50-5,000%; 50-1,000%; 50-750%; 50-500%; 50-250%; 50-100%; 50-75%; 75-100,000%; 75-75,000%; 75-50,000%; 75-25,000%; 75-10,000%; 75- 5,000%; 75-1,000%; 75-750%; 75-500%; 75-250%; 75-100%; 100-100,000%; 100-75,000%; 100-50,000%; 100-25,000%; 100-10,000%; 100-5,000%; 100-1,000%; 100-750%; 100-500%;100-250%; 250%-l,000%; 250%-750%; 250%-500%; 500%-l,000%; 500%-750%; 750%- 1,000%; 1,000%- 100, 000%; 1,000-75,000%; 1,000-50,000%; 1,000-25,000%; 1,000- 10,000%; 1,000-5,000%; 5,000-100,000%; 5,000-75,000%; 5,000-50,000%; 5,000-25,000%; 5,000-10,000%; 10,000-100,000%; 10,000-75,000%; 10,000-50,000%; 10,000-25,000%; 25,000-100,000%; 25,000-75,000%; 25,000-50,000%; 50,000-100,000%; 50,000-75,000% or 75,000-100,000%.

[0131] In some embodiments, signal is applied for an amount of time sufficient to allow for a decrease in the expression of a target molecule by about 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%; 25%; 30%; 40%; 50%; 60%; 70%; 75%; 80%; 90%; 100%; 125%; 150%; 175%; 200%; 250%; 300%; 400%; 500%; 600%; 700%; 750%; 800%; 900%; 1,000%; 2,000%; 2,500%; 3,000%; 4,000%; 5,000%; 6,000%; 7,000%; 7,500%; 8,000%; 9,000%; 10,000%; 20,000%; 25,000%; 30,000%; 40,000%; 50,000%; 60,000%; 70,000%; 75,000%; 80,000%; 85,000%; 90,000% or 100,000%; or a decrease in the expression of a target molecule by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, signal is applied for an amount of time sufficient to allow for a decrease in the expression of a target molecule by between about 1-100,000%; 1- 75,000%; 1-50,000%; 1-25,000%; 1-10,000%; 1-5,000%; 1-1,000%; 1-750%; 1-500%; 1- 250%; 1-100%; 1-75%; 1-50%; 1-25%; 1-10%; 1-5%; 5-100,000%; 5-75,000%; 5-50,000%; 5-25,000%; 5-10,000%; 5-5,000%; 5-1,000%; 5-750%; 5-500%; 5-250%; 5-100%; 5-75%; 5- 50%; 5-25%; 5-10%; 10-100,000%; 10-75,000%; 10-50,000%; 10-25,000%; 10-10,000%; 10- 5,000%; 10-1,000%; 10-750%; 10-500%; 10-250%; 10-100%; 10-75%; 10-50%; 10-25%; 25- 100,000%; 25-75,000%; 25-50,000%; 25-25,000%; 25-10,000%; 25-5,000%; 25-1,000%; 25- 750%; 25-500%; 25-250%; 25-100%; 25-75%; 25-50%; 50-100,000%; 50-75,000%; 50- 50,000%; 50-25,000%; 50-10,000%; 50-5,000%; 50-1,000%; 50-750%; 50-500%; 50-250%; 50-100%; 50-75%; 75-100,000%; 75-75,000%; 75-50,000%; 75-25,000%; 75-10,000%; 75- 5,000%; 75-1,000%; 75-750%; 75-500%; 75-250%; 75-100%; 100-100,000%; 100-75,000%; 100-50,000%; 100-25,000%; 100-10,000%; 100-5,000%; 100-1,000%; 100-750%; 100-500%; 100-250%; 250%-l,000%; 250%-750%; 250%-500%; 500%-l,000%; 500%-750%; 750%- 1,000%; 1,000%- 100, 000%; 1,000-75,000%; 1,000-50,000%; 1,000-25,000%; 1,000- 10,000%; 1,000-5,000%; 5,000-100,000%; 5,000-75,000%; 5,000-50,000%; 5,000-25,000%; 5,000-10,000%; 10,000-100,000%; 10,000-75,000%; 10,000-50,000%; 10,000-25,000%;25,000-100,000%; 25,000-75,000%; 25,000-50,000%; 50,000-100,000%; 50,000-75,000% or 75,000-100,000%.

[0132] In some embodiments, the signal is applied for an amount of time sufficient to allow for an increase in the expression of a target molecule by about 1-fold, 2-fold, 3 -fold,4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 250-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 750-fold, 800-fold, 900-fold or 1,000-fold, or for an amount of time sufficient to allow for an increase in the expression of a target molecule by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the signal is applied for an amount of time sufficient to allow for an increase in the expression of a target molecule by between about 1-fold to 1,000-fold, 1-fold to 750-fold, 1-fold to 500-fold, 1-fold to -250-fold, 1-fold to 100-fold, 1-fold to 75-fold, 1-fold to 50-fold, 1-fold to 25-fold, 1- fold to 10-fold, 1- fold to 7-fold, 1-fold to 5-fold, 1-fold to 3 -fold, 1-fold to 2-fold, 2-fold to 10- fold, 2-fold to 7-fold, 2-fold to 5-fold, 2-fold to 3-fold, 3-fold to 10-fold, 3-fold to 7-fold, 3- fold to 5-fold, 5-fold to 1,000-fold, 5-fold to 750-fold, 5-fold to 500-fold, 5-fold to -250-fold,5-fold to 100-fold, 5-fold to 75-fold, 5-fold to 50-fold, 5-fold to 25-fold, 5-fold to 10-fold, 5- fold to 7-fold, or 7-fold to 10-fold, 10-fold to 1,000-fold, 10-fold to 750-fold, 10-fold to 500- fold, 10-fold to 250-fold, 10-fold to 100-fold, 10-fold to 75-fold, 10-fold to 50-fold, 10-fold to 25-fold, 25-fold to 1,000-fold, 25-fold to 750-fold, 25-fold to 500-fold, 25-fold to 250-fold, 25-fold to 100-fold, 25-fold to 75-fold, 25-fold to 50-fold, 50-fold to 1,000-fold, 50-fold to 750-fold, 50-fold to 500-fold, 50-fold to 250-fold, 50-fold to 100-fold, 50-fold to 75-fold, 75- foldto 1,000-fold, 75-fold to 750-fold, 75-foldto 500-fold, 75-fold to 250-fold, 75-fold to 100- fold, 100-fold to 1,000-fold, 100-fold to 750-fold, 100-fold to 500-fold, 100-fold to 250-fold, 250-fold to 1,000-fold, 250-fold to 750-fold, 250-fold to 500-fold, 500-fold to 1,000-fold, 500- fold to 750-fold, or 750-fold to 1,000-fold, for an amount of time sufficient to allow for a decrease in the expression of a target molecule by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the signal is applied for an amount of time sufficient to allow for a decrease in the expression of a target molecule by between about 1-fold to 1,000-fold, 1-fold to 750-fold, 1-fold to 500-fold, 1-fold to -250-fold, 1-fold to 100-fold, 1-fold to 75-fold, 1-fold to 50-fold, 1-fold to 25-fold, 1- fold to 10-fold, 1- fold to 7-fold, 1-fold to 5-fold, 1-fold to 3-fold, 1-fold to 2-fold, 2-fold to 10-fold, 2-fold to 7-fold, 2-fold to 5-fold, 2-fold to 3-fold, 3-fold to 10-fold, 3-fold to 7-fold, 3-fold to 5-fold, 5- fold to 1,000-fold, 5-fold to 750-fold, 5-fold to 500-fold, 5-fold to -250-fold, 5-fold to 100- fold, 5-fold to 75-fold, 5-fold to 50-fold, 5-fold to 25-fold, 5-fold to 10-fold, 5-fold to 7-fold, or 7-fold to 10-fold, 10-fold to 1,000-fold, 10-fold to 750-fold, 10-fold to 500-fold, 10-fold to 250-fold, 10-fold to 100-fold, 10-fold to 75-fold, 10-fold to 50-fold, 10-fold to 25-fold, 25- fold to 1,000-fold, 25-fold to 750-fold, 25-fold to 500-fold, 25-fold to 250-fold, 25-fold to 100- fold, 25-fold to 75-fold, 25-fold to 50-fold, 50-fold to 1,000-fold, 50-fold to 750-fold, 50-fold to 500-fold, 50-fold to 250-fold, 50-fold to 100-fold, 50-fold to 75-fold, 75-fold to 1,000-fold, 75-fold to 750-fold, 75-fold to 500-fold, 75-fold to 250-fold, 75-fold to 100-fold, 100-fold to 1,000-fold, 100-fold to 750-fold, 100-fold to 500-fold, 100-fold to 250-fold, 250-fold to 1,000- fold, 250-fold to 750-fold, 250-fold to 500-fold, 500-fold to 1,000-fold, 500-fold to 750-fold, or 750-fold to 1,000-fold .

[0133] Some embodiments herein are directed to a method of programed conformational change. For example, FIG. 5 is a flow chart depicting some embodiments of a method of programmed conformational change 500. In some embodiments, a method of programmed conformational change 500 is disclosed. In some embodiments, the method 500 comprises applying a signal to a signal transducing element 501. In some embodiments, the signal transducing element and the thermosensitive element are chosen for their ability to transduce and receive a signal of a desired type. In some embodiments, the signal transducing element and the thermosensitive element are chosen for their ability to transduce and receive a signal comprising a desired characteristic, such as a specific signal strength or frequency. In some embodiments, the type of signal is chosen for its suitability for transduction between the signal transducing element and the thermosensitive element. In some embodiments, the strength of the signal is chosen for its ability to induce a desired conformational change upon transduction of the signal from the signal transducing particle to the thermosensitive particle. In some embodiments, the signal is applied intermittently. In some embodiments, the signal is applied continuously. In some embodiments, transduction of the signal to a thermosensitive element causes a change in the thermosensitive element 503.

[0134] In some embodiments, continued application of the signal or of a different signal results in one or more further conformational changes. In some embodiments, the signal is applied until 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conformational changes have occurred, or a numberof conformational changes that is in a range defined by any two of the preceding values. For example, in some embodiments, the signal is applied until between 1 to 10, 1 to 7, 1 to 5, 1 to 3, 1 to 2, 2 to 10, 2 to 7, 2 to 5, 2 to 3, 3 to 10, 3 to 7, 3 to 5, 5 to 10, 5 to 7, and 7 to 10 conformational changes have occurred. In some embodiments, application of the signal is ceased and / or a different signal is applied to revert the thermosensitive element to a nascent or intermediate conformation.

[0135] In some embodiments, transduction of the signal to the thermosensitive element increases the temperature of the thermosensitive element. In some embodiments, the signal is applied until the temperature of the thermosensitive element increases by about 0.1 °C, about 1°C, about 2°C, about 3°C, about 4°C, about 5°C, about 6°C, about 7°C, about 8°C, about 9°C, about 10°C, about 11°C, about 12°C, about 13°C, about 14°C, about 15°C, about 16°C, about 17°C, about 18°C, about 19°C, about 20°C, about 25°C, about 30°C, about 35°C, about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, about 65°C, about 70°C, about 75°C, about 80°C, about 85°C, about 90°C, about 95°C, or about 100°C, or by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the signal is applied until the temperature of the thermosensitive element increases by between about 0.1 °C to about 100°C, about 0.1 °C to about 75°C, about 0.1 °C to about 50°C, about 0.1 °C to about 25°C, about 0.1 °C to about 20°C, about 0.1 °C to about 10°C, about 0.1 °C to about 5°C, about 0.1 °C to about 1°C, about 1°C to about 100°C, about 1°C to about 75°C, about 1°C to about 50°C, about 1°C to about 25°C, about 1°C to about 20°C, about 1°C to about 10°C, about 1°C to about 5°C, about 5°C to about 100°C, about 5°C to about 75°C, about 5°C to about 50°C, about 5°C to about 25°C, about 5°C to about 20°C, about 5°C to about 10°C, about 10°C to about 100°C, about 10°C to about 75°C, about 10°C to about 50°C, about 10°C to about 25°C, about 10°C to about 20°C, about 20°C to about 100°C, about 20°C to about 75°C, about 20°C to about 50°C, about 20°C to about 25°C, about 25°C to about 100°C, about 25°C to about 75°C, about 25°C to about 50°C, about 50°C to about 100°C, about 50°C to about 75°C, or about 75°C to about 100°C.

[0136] In some embodiments, transduction of the signal to the thermosensitive element increases the free energy of the thermosensitive element. In some embodiments, the signal is applied until the free energy of the thermosensitive element has increased by about 0.01 Kcal / mol, about 0.05 Kcal / mol, about 0.1 Kcal / mol, about 0.5 Kcal / mol, about 0.9Kcal / mol, about 1 Kcal / mol, about 2 Kcal / mol, about 3 Kcal / mol, about 4 Kcal / mol, about 5 Kcal / mol, about 6 Kcal / mol, about 7 Kcal / mol, about 8 Kcal / mol, about 9 Kcal / mol, about 10 Kcal / mol, about 11 Kcal / mol, about 12 Kcal / mol, about 13 Kcal / mol, about 14 Kcal / mol, about 15 Kcal / mol, about 16 Kcal / mol, about 17 Kcal / mol, about 18 Kcal / mol, about 19 Kcal / mol, about 20 Kcal / mol, about 21 Kcal / mol, about 22 Kcal / mol, about 23 Kcal / mol, about 24 Kcal / mol, about 25 Kcal / mol, about 30 Kcal / mol, about 40 Kcal / mol, about 50 Kcal / mol, about 60 Kcal / mol, about 70 Kcal / mol, about 80 Kcal / mol, about 90 Kcal / mol, about 100 Kcal / mol, about 200 Kcal / mol, about 250 Kcal / mol, about 300 Kcal / mol, about 400 Kcal / mol, about 500 Kcal / mol, about 600 Kcal / mol, about 700 Kcal / mol, about 750 Kcal / mol, about 800 Kcal / mol, about 900 Kcal / mol, or about 1000 Kcal / mol, or by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, t the signal is applied until the free energy of the thermosensitive element has increased by between about 0.01 Kcal / mol to about 1000 Kcal / mol, about 0.01 Kcal / mol to about 750 Kcal / mol, about 0.01 Kcal / mol to about 500 Kcal / mol, about 0.01 Kcal / mol to about 250 Kcal / mol, about 0.01 Kcal / mol to about 100 Kcal / mol, about 0.01 Kcal / mol to about 75 Kcal / mol, about 0.01 Kcal / mol to about 50 Kcal / mol, about 0.01 Kcal / mol to about 25 Kcal / mol, about 0.01 Kcal / mol to about 20 Kcal / mol, about 0.01 Kcal / mol to about 15 Kcal / mol, about 0.01 Kcal / mol to about 10 Kcal / mol, about 0.01 Kcal / mol to about 5 Kcal / mol, about 0.01 Kcal / mol to about 1 Kcal / mol, about 0.01 Kcal / mol to about 0.1 Kcal / mol, about 0.1 Kcal / mol to about 1000 Kcal / mol, about 0.1 Kcal / mol to about 750 Kcal / mol, about 0.1 Kcal / mol to about 500 Kcal / mol, about 0.1 Kcal / mol to about 250 Kcal / mol, about 0.1 Kcal / mol to about 100 Kcal / mol, about 0.1 Kcal / mol to about 75 Kcal / mol, about 0.1 Kcal / mol to about 50 Kcal / mol, about 0.1 Kcal / mol to about 25 Kcal / mol, about 0.1 Kcal / mol to about 20 Kcal / mol, about 0.1 Kcal / mol to about 15 Kcal / mol, about 0.1 Kcal / mol to about 10 Kcal / mol, about 0.1 Kcal / mol to about 5 Kcal / mol, about 0.1 Kcal / mol to about 1 Kcal / mol, about 1 Kcal / mol to about 1000 Kcal / mol, about 1 Kcal / mol to about 750 Kcal / mol, about 1 Kcal / mol to about 500 Kcal / mol, about 1 Kcal / mol to about 250 Kcal / mol, about 1 Kcal / mol to about 100 Kcal / mol, about 1 Kcal / mol to about 75 Kcal / mol, about 1 Kcal / mol to about 50 Kcal / mol, about 1 Kcal / mol to about 25 Kcal / mol, about 1 Kcal / mol to about 20 Kcal / mol, about 1 Kcal / mol to about 15 Kcal / mol, about 1 Kcal / mol to about 10 Kcal / mol, about 1 Kcal / mol to about 5 Kcal / mol, about 5 Kcal / mol to about 1000 Kcal / mol, about 5 Kcal / mol to about 750 Kcal / mol, about 5 Kcal / molto about 500 Kcal / mol, about 5 Kcal / mol to about 250 Kcal / mol, about 5 Kcal / mol to about 100 Kcal / mol, about 5 Kcal / mol to about 75 Kcal / mol, about 5 Kcal / mol to about 50 Kcal / mol, about 5 Kcal / mol to about 25 Kcal / mol, about 5 Kcal / mol to about 20 Kcal / mol, about 5 Kcal / mol to about 15 Kcal / mol, about 5 Kcal / mol to about 10 Kcal / mol, about 10 Kcal / mol to about 1000 Kcal / mol, about 10 Kcal / mol to about 750 Kcal / mol, about 10 Kcal / mol to about 500 Kcal / mol, about 10 Kcal / mol to about 250 Kcal / mol, about 10 Kcal / mol to about 100 Kcal / mol, about 10 Kcal / mol to about 75 Kcal / mol, about 10 Kcal / mol to about 50 Kcal / mol, about 10 Kcal / mol to about 25 Kcal / mol, about 10 Kcal / mol to about 20 Kcal / mol, about 10 Kcal / mol to about 15 Kcal / mol, about 15 Kcal / mol to about 1000 Kcal / mol, about 15 Kcal / mol to about 750 Kcal / mol, about 15 Kcal / mol to about 500 Kcal / mol, about 15 Kcal / mol to about 250 Kcal / mol, about 15 Kcal / mol to about 100 Kcal / mol, about 15 Kcal / mol to about 75 Kcal / mol, about 15 Kcal / mol to about 50 Kcal / mol, about 15 Kcal / mol to about 25 Kcal / mol, about 15 Kcal / mol to about 20 Kcal / mol, about 20 Kcal / mol to about 1000 Kcal / mol, about 20 Kcal / mol to about 750 Kcal / mol, about 20 Kcal / mol to about 500 Kcal / mol, about 20 Kcal / mol to about 250 Kcal / mol, about 20 Kcal / mol to about 100 Kcal / mol, about 20 Kcal / mol to about 75 Kcal / mol, about 20 Kcal / mol to about 50 Kcal / mol, about 20 Kcal / mol to about 25 Kcal / mol, about 25 Kcal / mol to about 1000 Kcal / mol, about 25 Kcal / mol to about 750 Kcal / mol, about 25 Kcal / mol to about 500, about 25 Kcal / mol to about 250, about 25 Kcal / mol to about 100, about 25 Kcal / mol to about 75, about 25 Kcal / mol to about 50, about 50 Kcal / mol to about 1000, about 50 Kcal / mol to about 750 Kcal / mol, about 50 Kcal / mol to about 500 Kcal / mol, about 50 Kcal / mol to about 250 Kcal / mol, about 50 Kcal / mol to about 100 Kcal / mol, about 100 Kcal / mol to about 1000 Kcal / mol, about 100 Kcal / mol to about 750 Kcal / mol, about 100 Kcal / mol to about 500 Kcal / mol, about 100 Kcal / mol to about 250 Kcal / mol, about 250 Kcal / mol to about 1000 Kcal / mol, about 250 Kcal / mol to about 750 Kcal / mol, about 250 Kcal / mol to about 500 Kcal / mol, about 500 Kcal / mol to about 1000 Kcal / mol, about 500 Kcal / mol to about 750 Kcal / mol, or about 750 Kcal / mol to about 1000 Kcal / mol.

[0137] In some embodiments, application of the signal is ceased, allowing the temperature of the thermosensitive element to decrease. In some embodiments, application of the signal is ceased to allow the temperature of thermosensitive element to decrease by about 0.1 °C, about 0.5°C, about 1°C, about 2°C, about 3°C, about 4°C, about 5°C, about 6°C, about 7°C, about 8°C, about 9°C, about 10°C, about 11°C, about 12°C, about 13°C, about 14°C,about 15°C, about 16°C, about 17°C, about 18°C, about 19°C, about 20°C, about 25°C, about 30°C, about 35°C, about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, about 65°C, about 70°C, about 75°C, about 80°C, about 85°C, about 90°C, about 95°C, or about 100°C, or by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, the application of the signal is ceased until the temperature of the thermosensitive element decreases by between about 0.1 °C to about 100°C, about 0.1 °C to about 75°C, about 0.1 °C to about 50°C, about 0.1 °C to about 25°C, about 0.1 °C to about 20°C, about 0.1 °C to about 10°C, about 0.1 °C to about 5°C, about 0.1 °C to about 1°C, about 1°C to about 100°C, about 1°C to about 75°C, about 1°C to about 50°C, about 1°C to about 25°C, about 1°C to about 20°C, about 1°C to about 10°C, about 1°C to about 5°C, about 5°C to about 100°C, about 5°C to about 75°C, about 5°C to about 50°C, about 5°C to about 25°C, about 5°C to about 20°C, about 5°C to about 10°C, about 10°C to about 100°C, about 10°C to about 75°C, about 10°C to about 50°C, about 10°C to about 25°C, about 10°C to about 20°C, about 20°C to about 100°C, about 20°C to about 75°C, about 20°C to about 50°C, about 20°C to about 25°C, about 25°C to about 100°C, about 25°C to about 75°C, about 25°C to about 50°C, about 50°C to about 100°C, about 50°C to about 75°C, or about 75°C to about 100°C.

[0138] In some embodiments, application of the signal is ceased to allow the free energy of the thermosensitive element to decrease. In some embodiments, application of the signal is ceased until the free energy of the thermosensitive element has decreased by about 0.01 Kcal / mol, about 0.05 Kcal / mol, about 0.1 Kcal / mol, about 0.5 Kcal / mol, about 0.9 Kcal / mol, about 1 Kcal / mol, about 2 Kcal / mol, about 3 Kcal / mol, about 4 Kcal / mol, about 5 Kcal / mol, about 6 Kcal / mol, about 7 Kcal / mol, about 8 Kcal / mol, about 9 Kcal / mol, about 10 Kcal / mol, about 11 Kcal / mol, about 12 Kcal / mol, about 13 Kcal / mol, about 14 Kcal / mol, about 15 Kcal / mol, about 16 Kcal / mol, about 17 Kcal / mol, about 18 Kcal / mol, about 19 Kcal / mol, about 20 Kcal / mol, about 21 Kcal / mol, about 22 Kcal / mol, about 23 Kcal / mol, about 24 Kcal / mol, about 25 Kcal / mol, about 30 Kcal / mol, about 40 Kcal / mol, about 50 Kcal / mol, about 60 Kcal / mol, about 70 Kcal / mol, about 80 Kcal / mol, about 90 Kcal / mol, about 100 Kcal / mol, about 200 Kcal / mol, about 250 Kcal / mol, about 300 Kcal / mol, about 400 Kcal / mol, about 500 Kcal / mol, about 600 Kcal / mol, about 700 Kcal / mol, about 750 Kcal / mol, about 800 Kcal / mol, about 900 Kcal / mol, or about 1000 Kcal / mol, or by an amount that is in a range defined by any two of the preceding values. For example, in some embodiments, application of the signal isceased until the free energy of the thermosensitive element has decreased by between about 0.01 Kcal / mol to about 1000 Kcal / mol, about 0.01 Kcal / mol to about 750 Kcal / mol, about 0.01 Kcal / mol to about 500 Kcal / mol, about 0.01 Kcal / mol to about 250 Kcal / mol, about 0.01Kcal / mol to about 100 Kcal / mol, about 0.01 Kcal / mol to about 75 Kcal / mol, about 0.01Kcal / mol to about 50 Kcal / mol, about 0.01 Kcal / mol to about 25 Kcal / mol, about 0.01Kcal / mol to about 20 Kcal / mol, about 0.01 Kcal / mol to about 15 Kcal / mol, about 0.01Kcal / mol to about 10 Kcal / mol, about 0.01 Kcal / mol to about 5 Kcal / mol, about 0.01 Kcal / mol to about 1 Kcal / mol, about 0.01 Kcal / mol to about 0.1 Kcal / mol, about 0.1 Kcal / mol to about 1000 Kcal / mol, about 0.1 Kcal / mol to about 750 Kcal / mol, about 0.1 Kcal / mol to about 500 Kcal / mol, about 0.1 Kcal / mol to about 250 Kcal / mol, about 0.1 Kcal / mol to about 100 Kcal / mol, about 0.1 Kcal / mol to about 75 Kcal / mol, about 0.1 Kcal / mol to about 50 Kcal / mol, about 0.1 Kcal / mol to about 25 Kcal / mol, about 0.1 Kcal / mol to about 20 Kcal / mol, about 0.1 Kcal / mol to about 15 Kcal / mol, about 0.1 Kcal / mol to about 10 Kcal / mol, about 0.1 Kcal / mol to about 5 Kcal / mol, about 0.1 Kcal / mol to about 1 Kcal / mol, about 1 Kcal / mol to about 1000 Kcal / mol, about 1 Kcal / mol to about 750 Kcal / mol, about 1 Kcal / mol to about 500 Kcal / mol, about 1 Kcal / mol to about 250 Kcal / mol, about 1 Kcal / mol to about 100 Kcal / mol, about 1 Kcal / mol to about 75 Kcal / mol, about 1 Kcal / mol to about 50 Kcal / mol, about 1 Kcal / mol to about 25 Kcal / mol, about 1 Kcal / mol to about 20 Kcal / mol, about 1 Kcal / mol to about 15 Kcal / mol, about 1 Kcal / mol to about 10 Kcal / mol, about 1 Kcal / mol to about 5 Kcal / mol, about 5 Kcal / mol to about 1000 Kcal / mol, about 5 Kcal / mol to about 750 Kcal / mol, about 5 Kcal / mol to about 500 Kcal / mol, about 5 Kcal / mol to about 250 Kcal / mol, about 5 Kcal / mol to about 100 Kcal / mol, about 5 Kcal / mol to about 75 Kcal / mol, about 5 Kcal / mol to about 50 Kcal / mol, about 5 Kcal / mol to about 25 Kcal / mol, about 5 Kcal / mol to about 20 Kcal / mol, about 5 Kcal / mol to about 15 Kcal / mol, about 5 Kcal / mol to about 10 Kcal / mol, about 10 Kcal / mol to about 1000 Kcal / mol, about 10 Kcal / mol to about 750 Kcal / mol, about 10 Kcal / mol to about 500 Kcal / mol, about 10 Kcal / mol to about 250 Kcal / mol, about 10 Kcal / mol to about 100 Kcal / mol, about 10 Kcal / mol to about 75 Kcal / mol, about 10 Kcal / mol to about 50 Kcal / mol, about 10 Kcal / mol to about 25 Kcal / mol, about 10 Kcal / mol to about 20 Kcal / mol, about 10 Kcal / mol to about 15 Kcal / mol, about 15 Kcal / mol to about 1000 Kcal / mol, about 15 Kcal / mol to about 750 Kcal / mol, about 15 Kcal / mol to about 500 Kcal / mol, about 15 Kcal / mol to about 250 Kcal / mol, about 15 Kcal / mol to about 100 Kcal / mol, about 15 Kcal / mol to about 75Kcal / mol, about 15 Kcal / mol to about 50 Kcal / mol, about 15 Kcal / mol to about 25 Kcal / mol, about 15 Kcal / mol to about 20 Kcal / mol, about 20 Kcal / mol to about 1000 Kcal / mol, about 20 Kcal / mol to about 750 Kcal / mol, about 20 Kcal / mol to about 500 Kcal / mol, about 20 Kcal / mol to about 250 Kcal / mol, about 20 Kcal / mol to about 100 Kcal / mol, about 20 Kcal / mol to about 75 Kcal / mol, about 20 Kcal / mol to about 50 Kcal / mol, about 20 Kcal / mol to about 25 Kcal / mol, about 25 Kcal / mol to about 1000 Kcal / mol, about 25 Kcal / mol to about 750 Kcal / mol, about 25 Kcal / mol to about 500, about 25 Kcal / mol to about 250, about 25 Kcal / mol to about 100, about 25 Kcal / mol to about 75, about 25 Kcal / mol to about 50, about 50 Kcal / mol to about 1000, about 50 Kcal / mol to about 750 Kcal / mol, about 50 Kcal / mol to about 500 Kcal / mol, about 50 Kcal / mol to about 250 Kcal / mol, about 50 Kcal / mol to about 100 Kcal / mol, about 100 Kcal / mol to about 1000 Kcal / mol, about 100 Kcal / mol to about 750 Kcal / mol, about 100 Kcal / mol to about 500 Kcal / mol, about 100 Kcal / mol to about 250 Kcal / mol, about 250 Kcal / mol to about 1000 Kcal / mol, about 250 Kcal / mol to about 750 Kcal / mol, about 250 Kcal / mol to about 500 Kcal / mol, about 500 Kcal / mol to about 1000 Kcal / mol, about 500 Kcal / mol to about 750 Kcal / mol, or about 750 Kcal / mol to about 1000 Kcal / mol.Exemplary applications for constructs and methods for expression or regulation of a target molecule

[0139] There are applications for embodiments of the constructs and methods disclosed herein, including in, but not limited to, gene / electronic circuit interfacing and simplified in vivo gene activation. For example, in neuroscience / neuroengineering, local protein synthesis driven by mRNA trafficking within neurons is highly pathologically relevant. However, study of the peripheral nervous system is significantly limited by its location deep within the tissues. Current approaches, including AAV Cre-ER constructs, have limited spatial specificity or fail to target myelinated fibers. In some embodiments, the methods and constructs described herein have an application in the driving of local protein synthesis specific to an area of interest independent of tissue accessibility or myelination. Additionally, the methods and constructs may allow for simplified, reversible, and fine-tunable nerve blocks and nerve stimulation.

[0140] In some embodiments, the constructs and methods described herein have applications in biological / electronic interfacing. The constructs and methods disclosed hereinenable other applications that require a robust machine - organism interface. Industrial applications of expression and lysis enable high-volume biologic production for pharmaceuticals and research. AMF induction of protein expression using RNA thermometry would incur faster responses than expensive chemical induction, which requires new RNA to be transcribed. A construct, such as those disclosed herein, expressing a lytic toxin could be used to rapidly lyse cells upon exposure to a signal, for example, but not limited to, AMF, which resolves the need for homogenization or sonication that may reduce yields. The quick response times of the constructs disclosed herein are well-suited to biocontainment applications. A construct expressing a non-lytic toxin such as MazF, upon exposure to a signal, for example, but not limited to, AMF, could quickly kill cells when necessary. Alternatively, a construct expressing a repressor, such as TetR, in response to a signal, for example, but not limited to, AMF, that normally represses non-lytic toxin, could be used to sustain cells in the signal and kill any escaping containment.

[0141] In some embodiments, the constructs and methods described herein have applications in immunoengineering. For example, integration of magneto-genetic gene circuitry into immune cell therapies promotes immunostimulation and immunoinhibition. Ex vivo engineered CAR-T cells provide the ability to activate anti-tumor gene cassettes at and only at the site of cancer (as pinpointed with EMS). Inversely, constructs allowing for localized electromagnetic immunostimulation and immunoinhibition may be built into regulatory T cells to allow for localized immunosuppression at sites affected by autoimmune disorders (e.g., arthritic joint) or organ transplantation (e.g., transplanted liver) without shutting down the entire immune system.Numbered Arrangements:

[0142] Some embodiments provided herein are described by way of the following provided numbered arrangements, and are also provided as possible combinations or overlapping embodiments:1. A construct for expression or regulation of a target molecule, the construct comprising: a thermosensitive element, and a signal transducing element;wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element; and wherein the conformational change in the thermosensitive element allows expression or regulation of a target molecule.2. The construct of arrangement 1, wherein the thermosensitive element comprises a nucleic acid.3. The construct of arrangement 2, wherein the nucleic acid is RNA or DNA.4. The construct of arrangement 1, wherein the thermosensitive element comprises a protein.5. The construct of any one of arrangements 1 -4, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.6. The construct of any one of arrangements 1 -4, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), and any combination thereof.7. The construct of any one of arrangements 1-6, wherein the signal transducing element is selected from the group comprising a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, a protein complex, and any combination thereof.8. The construct of any one of arrangements 1-6, wherein the signal transducing element comprises a ferritin nanoparticle.9. The construct of any one of arrangements 1-6, wherein the signal transducing element comprises an oxidized nanoparticle.10. The construct of arrangement 9, wherein the oxidized nanoparticle is an iron oxide nanoparticle.11. The construct of any one of arrangements 1-10, wherein the signal comprises a tissue penetrating signal.12. The construct of any one of arrangements 1-10, wherein the signal comprises a wireless signal.13. The construct of any one of arrangements 1-12, wherein the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof.14. The construct of any one of arrangements 1-12, wherein the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz.15. The construct of arrangement 13, wherein the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz.16. The construct of any one of arrangements 1-12, wherein the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m.17. The construct of arrangement 16, wherein the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m.18. The construct of any one of arrangements 1-17, wherein transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element.19. The construct of any one of arrangements 1-17, wherein transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element.20. The construct of arrangement 19, wherein the temperature increases by between about 0.1 °C and 35 °C.21. The construct of any one of arrangements 1-17, wherein transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element.22. The construct of arrangement 21, wherein the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol.23. The construct of arrangement 22, wherein the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.24. The construct of any one of arrangements 1-23, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered capindependent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.25. The construct of any one of arrangements 1-24, wherein the temperature of the thermosensitive element decreases following cessation of the signal.26. The construct of any one of arrangements 1-25, further comprising a linker.27. The construct of any one of arrangements 1-26, wherein regulation of a target molecule comprises obstruction or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element.28. The construct of any one of arrangements 1-26, wherein regulation of a target molecule comprises obstruction or de-obstruction of one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered capindependent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.29. The construct of any one of arrangements 1-26, wherein regulation of a target molecule comprises obstruction or de-obstruction of one or more genetic elements selected from the group comprising: Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), and any combination thereof.30. A construct for programmed conformational change, the construct comprising: a thermosensitive element, and a signal transducing element; wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; and wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element.31. The construct of arrangement 30, wherein the conformational change in the thermosensitive element obstructs one or more genetic elements.32. The construct of either arrangement 30 or 31, wherein the conformational change in the thermosensitive element de-obstructs one or more genetic elements.33. The construct of any one of arrangements 30-32, wherein the thermosensitive element comprises a nucleic acid.34. The construct of arrangement 33, wherein the nucleic acid is RNA or DNA.35. The construct of any one of arrangements 30-32, wherein the thermosensitive element comprises a protein.36. The construct of any one of arrangements 30-35, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.37. The construct of any one of arrangements 30-35, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising Shine- Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and capindependent translation enhancers (CITEs), and any combination thereof.38. The construct of any one of arrangements 30-37, wherein the signal transducing element is selected from the group comprising: a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, a protein complex, and any combination thereof.39. The construct of any one of arrangements 30-37, wherein the signal transducing element comprises a ferritin nanoparticle.40. The construct of any one of arrangements 30-37, wherein the signal transducing element comprises an oxidized nanoparticle.41. The construct of arrangement 40, wherein the oxidized nanoparticle is an iron oxide nanoparticle.42. The construct of any one of arrangements 30-41, wherein the signal comprises a tissue penetrating signal.43. The construct of any one of arrangements 30-41, wherein the signal comprises a wireless signal.44. The construct of any one of arrangements 30-43, wherein the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof.45. The construct of any one of arrangements 30-43, wherein the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz.46. The construct of arrangement 45, wherein the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz.47. The construct of any one of arrangements 30-43, wherein the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m.48. The construct of arrangement 47, wherein the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m.49. The construct of any one of arrangements 30-48, wherein transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element.50. The construct of any one of arrangements 30-49, wherein transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element.51. The construct of arrangement 50, wherein the temperature increases by between about 0.1 °C and 35 °C.52. The construct of any one of arrangements 30-51, wherein transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element.53. The construct of arrangement 52, wherein the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol.54. The construct of arrangement 53, wherein the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.55. The construct of any one of arrangements 30-54, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.56. The construct of arrangement 55, wherein obstruction or de-obstruction of one or more genetic elements alters expression or regulation of one or more target molecules.57. The construct of arrangement 56, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.58. The construct of arrangement 57, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.59. The construct of arrangement 57, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.60. The construct of arrangement 57, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.61. The construct of arrangement 57, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.62. The construct of arrangement 61, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.63. The construct of arrangement 61, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.64. The construct of arrangement 61, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.65. The construct of arrangement 61, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.66. The construct of arrangement 56, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.67. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.68. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.69. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.70. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000%.71. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.72. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.73. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.74. The construct of arrangement 66, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.75. The construct of any one of arrangements 30-74, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more DNA, RNA, or protein binding sites on the thermosensitive element.76. The construct of arrangement 75, wherein obstruction or de-obstruction of one or more DNA, RNA, or protein binding sites on the thermosensitive element alters expression or regulation of one or more target molecules.77. The construct of arrangement 76, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.78. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.79. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.80. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.81. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.82. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.83. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.84. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.85. The construct of arrangement 77, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.86. The construct of arrangement 76, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.87. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.88. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.89. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.90. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.91. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.92. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.93. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.94. The construct of arrangement 86, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.95. The construct of any one of arrangements 30-94, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), and any combination thereof.96. The construct of arrangement 95, wherein obstruction or de-obstruction of one or more genetic elements selected from the group comprising Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), and any combination thereof, alters expression or regulation of one or more target molecules.97. The construct of arrangement 96, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.98. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.99. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.100. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.101. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.102. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.103. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.104. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.105. The construct of arrangement 97, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.106. The construct of arrangement 96, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.107. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.108. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.109. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.110. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.111. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.112. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.113. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.114. The construct of arrangement 106, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.115. The construct of any one of arrangements 30-114, wherein the temperature of the thermosensitive element decreases following cessation of the signal.116. The construct of any one of arrangements 30-115, further comprising a linker.117. A gene expression construct comprising: a thermosensitive nucleic acid, and a magnetically-susceptible nanoparticle; wherein the thermosensitive nucleic acid is configured to change confirmations upon transduction of a signal from the magnetically-susceptible nanoparticle to the thermosensitive nucleic acid.118. The gene expression construct of arrangement 117, wherein the thermosensitive element comprises a nucleic acid.119. The gene expression construct of arrangement 118, wherein the nucleic acid is RNA or DNA.120. The construct of arrangement 117, wherein the thermosensitive element comprises a protein.121. The gene expression construct of any one of arrangements 117-120, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, stericallyhindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.122. The gene expression construct of any one of arrangements 117-120, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), and any combination thereof.123. The gene expression construct of any one of arrangements 117-122, wherein the signal transducing element is selected from the group comprising: a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, a protein complex, and any combination thereof.124. The gene expression construct of any one of arrangements 117-122, wherein the signal transducing element comprises a ferritin nanoparticle.125. The gene expression construct of any one of arrangements 117-122, wherein the signal transducing element comprises an oxidized nanoparticle.126. The gene expression construct of arrangement 125, wherein the oxidized nanoparticle is an iron oxide nanoparticle.127. The gene expression construct of any one of arrangements 117-126, wherein the signal comprises a tissue penetrating signal.128. The gene expression construct of any one of arrangements 117-126, wherein the signal comprises a wireless signal.129. The gene expression construct of any one of arrangements 117-128, wherein the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof.130. The gene expression construct of any one of arrangements 117-128, wherein the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz.131. The gene expression construct of arrangement 130, wherein the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz.132. The gene expression construct of any one of arrangements 117-131, wherein the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m.133. The gene expression construct of arrangement 132, wherein the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m.134. The gene expression construct of any one of arrangements 117-133, wherein transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element.135. The gene expression construct of any one of arrangements 117-134, wherein transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element.136. The gene expression construct of arrangement 135, wherein the temperature increases by between about 0.1 °C and 35 °C.137. The gene expression construct of any one of arrangements 117-136, wherein transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element.138. The gene expression construct of arrangement 137, wherein the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol.139. The gene expression construct of arrangement 138, wherein the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.140. The gene expression construct of any one of arrangements 117-139, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.141. The gene expression construct of arrangement 140, wherein obstruction or deobstruction of one or more genetic elements alters expression or regulation of one or more genes.142. The construct of arrangement 141, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.143. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.144. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.145. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.146. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.147. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.148. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.149. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.150. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.151. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.152. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.153. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.154. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.155. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.156. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.157. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.158. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.159. The construct of arrangement 142, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.160. The gene expression construct of any one of arrangements 117-139, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more DNA, RNA, or protein binding sites on the thermosensitive element.161. The gene expression construct of arrangement 160, wherein obstruction or de- obstruction of one or more DNA, RNA, or protein binding sites on the thermosensitive element, alters expression or regulation of one or more genes.162. The construct of arrangement 161, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.163. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.164. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.165. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.166. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.167. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.168. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.169. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.170. The construct of arrangement 162, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.171. The construct of arrangement 161, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.172. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.173. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.174. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.175. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.176. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.177. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.178. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.179. The construct of arrangement 171, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.180. The gene expression construct of any one of arrangements 117-139, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), or any combination thereof.181. The gene expression construct of arrangement 180, wherein obstruction or de- obstruction of one or more genetic elements selected from the group comprising: Shine- Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and capindependent translation enhancers (CITEs), or any combination thereof, alters expression or regulation of one or more genes.182. The construct of arrangement 181, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.183. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.184. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.185. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.186. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.187. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.188. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.189. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.190. The construct of arrangement 182, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.191. The construct of arrangement 181, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.192. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.193. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.194. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.195. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.196. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.197. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.198. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.199. The construct of arrangement 191, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.200. The gene expression construct of any one of arrangements 117-199, wherein the temperature of the thermosensitive element decreases following cessation of the signal.201. The gene expression construct of any one of arrangements 117-200, further comprising a linker.202. A method of expressing or regulating a target molecule, the method comprising: administering a construct for expression or regulation of a target molecule to a subject, the construct comprising: a thermosensitive element, and a signal transducing element; and applying a signal to the signal transducing element.203. The method of arrangement 202, wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element.204. The method of arrangement 203, wherein the conformational change in the thermosensitive element alters expression or regulation of a target molecule.205. The method of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.206. The method of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.207. The construct of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.208. The construct of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.209. The method of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.210. The construct of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.211. The construct of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.212. The construct of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.213. The construct of arrangement 204, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.214. The method of arrangement 203, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.215. The method of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.216. The construct of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.217. The construct of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.218. The method of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.219. The construct of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.220. The construct of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.221. The construct of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.222. The construct of arrangement 214, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.223. The method of any one of arrangements 202-222, wherein altered expression or regulation of a target molecules activates or deactivates one or more molecular processes.224. The method of arrangement 223, wherein the molecular process comprises a spatial or temporal: upregulation or downregulation of gene expression, upregulation or downregulation of metabolic pathways, localization of cells within a body, immunologicalstimulation of target regions, immunosuppression of target regions, and any combination thereof.225. The method of any one of arrangements 202-224, wherein the thermosensitive element comprises a nucleic acid.226. The method of arrangement 225, wherein the nucleic acid is RNA or DNA.227. The method of any one of arrangements 202-224, wherein the thermosensitive element comprises a protein.228. The method of any one of arrangements 202-224, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.229. The method of any one of arrangements 202-224, wherein the thermosensitive element comprises one or more Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), and any combination thereof.230. The method of any one of arrangements 202-229, wherein the signal transducing element is selected from the group comprising: a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, a protein complex, and any combination thereof.231. The method of any one of arrangements 202-229, wherein the signal transducing element comprises a ferritin nanoparticle.232. The method of any one of arrangements 202-229, wherein the signal transducing element comprises an oxidized nanoparticle.233. The method of arrangement 232, wherein the oxidized nanoparticle is an iron oxide nanoparticle.234. The method of any one of arrangements 202-233, wherein the signal comprises a tissue penetrating signal.235. The method of any one of arrangements 202-233, wherein the signal comprises a wireless signal.236. The method of any one of arrangements 202-233, wherein the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof.237. The method of any one of arrangements 202-233, wherein the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz.238. The method of arrangement 234, wherein the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz.239. The method of any one of arrangements 202-233, wherein the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m.240. The method of arrangement 239, wherein the signal comprises an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m.241. The method of any one of arrangements 202-240, wherein transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element.242. The method of any one of arrangements 202-241, wherein transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element.243. The method of arrangement 242, wherein the temperature increases by between about 0.1 °C and 35 °C.244. The method of any one of arrangements 202-243, wherein transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element.245. The method of arrangement 244, wherein the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol.246. The method of arrangement 245, wherein the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.247. The method of any one of arrangements 202-246, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, stericallyhindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.248. The method of arrangement 247, wherein obstruction or de-obstruction of one or more genetic elements alters expression or regulation of one or more genes.249. The method of arrangement 248, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.250. The method of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.251. The construct of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.252. The construct of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.253. The method of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.254. The construct of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.255. The construct of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.256. The construct of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.257. The construct of arrangement 249, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.258. The method of arrangement 248, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.259. The method of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.260. The construct of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.261. The construct of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.262. The method of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.263. The construct of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.264. The construct of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.265. The construct of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.266. The construct of arrangement 258, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.267. The method of any one of arrangements 202-246, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more DNA, RNA, or protein binding sites on the thermosensitive element.268. The method of arrangement 267, wherein obstruction or de-obstruction of one or more DNA, RNA, or protein binding sites on the thermosensitive element, alters expression or regulation of one or more genes.269. The method of arrangement 268, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.270. The method of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.271. The construct of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.272. The construct of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.273. The method of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.274. The construct of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.275. The construct of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.276. The construct of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.277. The construct of arrangement 269, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.278. The method of arrangement 268, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.279. The method of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.280. The construct of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.281. The construct of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.282. The method of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.283. The construct of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.284. The construct of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.285. The construct of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.286. The construct of arrangement 278, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.287. The method of any one of arrangements 202-246, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more Shine-Dalgarnosequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), or any combination thereof.288. The method of arrangement 287, wherein obstruction or de-obstruction of one or more genetic elements selected from the group comprising: Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), or any combination thereof, alters expression or regulation of one or more genes.289. The method of arrangement 288, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.290. The method of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.291. The construct of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.292. The construct of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.293. The method of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.294. The construct of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.295. The construct of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.296. The construct of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.297. The construct of arrangement 289, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.298. The method of arrangement 288, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.299. The method of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.300. The construct of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.301. The construct of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.302. The method of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.303. The construct of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.304. The construct of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.305. The construct of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.306. The construct of arrangement 298, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.307. The method of any one of arrangements 202-306, wherein the temperature of the thermosensitive element decreases following cessation of the signal.308. A method of programed conformational change, the method comprising: applying a signal to a signal transducing element; wherein transduction of the signal to a thermosensitive element causes a conformational change in the thermosensitive element.309. The method of arrangement 308, wherein the conformational change in the thermosensitive element allows expression or regulation of a target molecule.310. The method of either arrangement 308 or 309, further comprising monitoring expression or regulation of the target molecule.311. The method of arrangement 310, wherein altered expression or regulation of the target molecule indicates ballistic energy transfer from the signal transducing element to the thermosensitive element.312. The method of arrangement 310, wherein altered expression or regulation of a target molecules activates or deactivates one or more molecular processes.313. The method of arrangement 312, wherein the molecular process comprises a spatial or temporal: upregulation / downregulation of gene expression or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof.314. The method of any one of arrangements 308-313, wherein the thermosensitive element comprises a nucleic acid.315. The method of arrangement 314, wherein the nucleic acid is RNA or DNA.316. The method of any one of arrangements 308-313, wherein the thermosensitive element comprises a protein.317. The method of any one of arrangements 308-313, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.318. The method of any one of arrangements 308-313, wherein the thermosensitive element is selected from the group comprising: one or more Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs), cap-independent translation enhancers (CITEs), and any combination thereof.319. The method of any one of arrangements 308-319, wherein the signal transducing element is selected from the group comprising a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, or a protein complex, and any combination thereof.320. The method of any one of arrangements 308-319, wherein the signal transducing element comprises a ferritin nanoparticle.321. The method of any one of arrangements 308-319, wherein the signal transducing element comprises an oxidized nanoparticle.322. The method of arrangement 321, wherein the oxidized nanoparticle is an iron oxide nanoparticle.323. The method of any one of arrangements 308-322, wherein the signal comprises a tissue penetrating signal.324. The method of any one of arrangements 308-323, wherein the signal comprises a wireless signal.325. The method of any one of arrangements 308-324, wherein the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof.326. The method of any one of arrangements 308-325, wherein the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz.327. The method of arrangement 326, wherein the signal comprises an alternating magnetic field at a frequency of up to about 250 MHz.328. The method of any one of arrangements 308-325, wherein the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m.329. The method of arrangement 328, wherein the signal comprises an alternating magnetic field at a field strength of about 10 kA / m and about 20 kA / m.330. The method of any one of arrangements 308-329, wherein transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element.331. The method of any one of arrangements 308-330, wherein transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element.332. The method of arrangement 331, wherein the temperature increases by between about 0.1 °C and 35 °C.333. The method of any one of arrangements 308-332, wherein transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element.334. The method of arrangement 333, wherein the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol.335. The method of arrangement 334, wherein the free energy (AG) increases by between about 1 Kcal / mol and about 15 Kcal / mol.336. The method of any one of arrangements 308-335, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.337. The method of arrangement 336, wherein obstruction or de-obstruction of one or more genetic elements alters expression or regulation of one or more genes.338. The method of arrangement 337, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.339. The method of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.340. The construct of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.341. The construct of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.342. The method of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.343. The construct of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.344. The construct of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.345. The construct of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.346. The construct of arrangement 338, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.347. The method of arrangement 337, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.348. The method of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.349. The construct of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.350. The construct of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.351. The method of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.352. The construct of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.353. The construct of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.354. The construct of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.355. The construct of arrangement 347, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.356. The method of any one of arrangements 308-335, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more DNA, RNA, or protein binding sites on the thermosensitive element.357. The method of arrangement 356, wherein obstruction or de-obstruction of one or more DNA, RNA, or protein binding sites on the thermosensitive element, alters expression or regulation of one or more genes.358. The method of arrangement 357, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.359. The method of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.360. The construct of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.361. The construct of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.362. The method of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.363. The construct of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.364. The construct of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.365. The construct of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.366. The construct of arrangement 358, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.367. The method of arrangement 357, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.368. The method of arrangement 367, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.369. The construct of arrangement 367, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.370. The construct of arrangement 367, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.371. The method of arrangement 367, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.372. The method of any one of arrangements 308-335, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), or any combination thereof.373. The method of arrangement 372, wherein obstruction or de-obstruction of one or more genetic elements selected from the group comprising: Shine-Dalgarno sequences, Kozak sequences, internal ribosomal entry sites (IRESs) and cap-independent translation enhancers (CITEs), or any combination thereof, alters expression or regulation of one or more genes.374. The method of arrangement 373, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.375. The method of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-5 fold.376. The construct of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100 fold.377. The construct of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1,000 fold.378. The method of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 1000%.379. The construct of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 5,000%.380. The construct of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 10,000%.381. The construct of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 50,000%.382. The construct of arrangement 374, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1- 100,00%.383. The method of arrangement 373, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.384. The method of arrangement 383, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-5 fold.385. The construct of arrangement 383, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100 fold.386. The construct of arrangement 383, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1,000 fold.387. The method of arrangement 383, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 1000%.388. The construct of arrangement 383 , wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 5,000%.389. The construct of arrangement 383, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 10,000%.390. The construct of arrangement 383, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 50,000%.391. The construct of arrangement 383, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1- 100,00%.392. The method of any one of arrangements 308-391, wherein the temperature of the thermosensitive element decreases following cessation of the signal.EXAMPLESExample 1 : Localized Electromagnetic Immunostimulation and Inhibition (LEMHI

[0143] The use of electromagnetic stimulation to trigger a circuit within the body to only release immunosuppressive antibodies to a specific site in the body is examined and is described in this non-limiting example.

[0144] IL-6 cytokines are essential for the acquired immune response and the acute phase response. IL-6 recruits immune cells and promotes specific differentiation of CD4+ T- cells. However, the dysregulation of IL-6 is often associated with inflammatory diseases such as Rheumatoid arthritis and Juvenile idiopathic arthritis, along with Cytokine Release Syndrome, which commonly occurs during CAR-T cell therapy and is a reason for the inflammation experienced during Covid- 19. IL-6 is a characterized target for treating immune- mediated diseases. The drug Tocilizumab is an IL-6 blocker and has been used for the treatment of Rheumatoid arthritis and severe inflammation from Covid-19. However, it lacks localization and once inside the body, the tocilizumab-produced antibodies cannot be regulated. This has the potential to disrupt the body’s acquired immune response beyond the area of inflammation. We seek to find a biological solution that will block IL-6 under spatiotemporal regulation.

[0145] Spatiotemporal regulation of gene expression is invaluable for both characterizing the activity of genes in vivo and therapeutic purposes. Lor the purpose of gene therapy, transgenes are especially important to regulate. Transgene regulation has been doneusing small molecule inducers. However, these inducers cannot be easily localized or turned on or off. The field of optogenetics has created methods to regulate inducers and genes directly using UV and infrared laser light. However, light has limited penetration and limits the area of activation. Therefore, for the purpose of IL-6 blockage, we seek to find a method of anti-IL-6 transgene regulation that can be targeted in any area of the human body utilizing permeating electromagnetic radiation.

[0146] There are two main types of IL-6 inhibitors that are used in anti-IL-6 treatment - anti-IL-6 receptor monoclonal antibodies, and anti-IL-6 monoclonal antibodies, which simply function by binding to IL-6 rather than the receptor. The most common examples of anti-IL-6R mAbs are tocilizumab and sarilumab, while siltuximab is a recombinant anti-IL- 6 mAb. These inhibitors are used as forms of systemic immunosuppression, which pose challenges due to the side effects (particularly infection) caused by the toxicity of the drugs used subsequent disruption of immune response in non-targeted areas. Localized immunosuppression thus offers a safer method of treatment and has shown promise following several surgical procedures including VCA (vascularized composite allografts) and islet transplantation. Clinical outcomes indicate lower systemic drug levels and toxicity, reduced side effects and mortality rates, and increased graft acceptance for the former procedure. Regarding IL-6 specifically, both clinical and observational studies have exhibited that severe infections are prevalent and serious consequences of systemic anti-IL-6 treatments, suggesting that a localized anti-IL-6 procedure would be an ideal alternative.

[0147] This experiment was designed to test the use electromagnetic radiation (EM) to cause a physical change in a heat sensitive aptamer or protein to control the translation of an IL-6 antagonist (aIL-6) insert.

[0148] The spatial-temporal specificity of the EM signaling method is examined. For example, how quickly the signal will turn on and off aIL-6 production, and how much time a heat transformer needs to reset before it can receive another signal are determined. Additionally, the range of efficacy for the EM signals is determined. Finally, a determination of which wavelength and frequency most reliably induce a response in target cells at different depths within the body are examined.

[0149] An AND GATE is created by combining an RNA thermometer and a toehold switch. The toehold switch is designed in a way such that the RNA thermometer, whichwill be annealed to the toehold switch in later stages, will not interfere with folding. The RNA thermometer design involves attaching a ferritin nanoparticle to the trigger so that the RNA thermometer will unravel when the ferritin heats up. Additionally, the order of activation for the toehold switch and RNA thermometer may interfere with the function of each component. As the RNA unfolds as each segment is activated, the change in shape could interfere with the activation of the second component, such as blocking a trigger site, or moving the ferritin out of position. Therefore, the mRNA sequence is designed such that, when folded, the ferritin will be close enough to the RNA thermometer that the nanoparticle transfers activates the thermometer efficiently without interfering with the toehold switch. To do this, folding and heating patterns are examined to determine where on the sequence to place the nanoparticle.

[0150] As for the production of aIL-6 itself, a method of synthesis, such as synthesizing an antibody / antagonist, or by taking advantage of the body’s natural regulatory pathways, may be used. A feedback loop is created in the aIL-6 production plasmid to regulate the production of aIL-6 using factors like the local concentration of IL-6 near the transfected cells, or the production of IL-6 response elements inside the cells.System Architecture:

[0151] The general structure of a system and its two contrasting development stagings are described, in this non-limiting example, as follows:

[0152] FIG. 9A is an illustration depicting the LEMII System Architecture.

[0153] IL-6 Sensing: Although the development of the IL-6 Sensing would occur later in the project, introducing it first helps to understand the remainder of the work. A variety of means to assess IL-6 were evaluated; however, the use of the IL-6-related transcription factor NF-KB simplified circuit design significantly. The NF-KB family consists of transcription factors that are associated with pro-inflammatory pathways, in which IL-6 is prominent. A subset of NF-KB factors are analyzed to further hone the specificity of the system. Additionally, mRNA produced as a result of NF-KB -promoted transcription may also be used as a marker.Ferritin-MCP and MS2-based Electromagnetic Reception:

[0154] FIG. 10 is a schematic showing a construct comprising an NP-RNAT or Ferritin-RNAT based AND GATE, according to some embodiments. A Chemically Induced Promoter [I] (e.g., Chemically Induced Dimerization-type system; for development purposes, this may be added in late stage iteration) initiates transcription and translation of Ferritin-MCP and transcription of the MS2-Thermosensitive Aptamer-Transcription Factor (TF) aptamer. Upon conjugation of the 2 entities, the electromagnetic excitement [II] of the ferritin induces relaxation of the MS2-Thermosensitive Aptamer-Transcription Factor (TF) aptamer and expression of TF, promoting the Transcription Factor Response Element (TF RE). This triggers the expression of miRNA 1 respective to mRNA w / the miR-1 RE. In parallel, high extracellular IL-6 concentrations [III] stimulate the transcription factor NF-kB that triggers synthesis of miRNA 2 by binding its response element. These miRNA work independently to inhibit two separate copies of L7Ae, a repressor of the anti-IL-6 through Kt binding. By inhibiting both copies of the repressor, an effective AND GATE is created, and the aIL-6 is transcribed.Aptamer-based Electromagnetic Reception:

[0155] An aptamer containing regions for both a RNA thermometer and toehold switch bound to ferritin via an RNA-binding protein is produced and is described in this nonlimiting example. When structured correctly, this aptamer functions as an RNA-based AND GATE, requiring both inputs of EM and the Toehold Trigger Sequence (correlated to IL-6 concentration and signaling). When stimulated by both EM (and locally generated heat) and IL-6 correlated Toehold Trigger Sequence, both segments of the aptamer will unhold, revealing a previously obstructed IRES and Translation Start Site (AUG).

[0156] FIG. 11A-C is a series of schematics showing a construct comprising an aptamer comprising disjointed RNA thermometer (RNAT) and toehold switch components, according to some embodiments. FIG. 11 A is a schematic showing a construct for expressing a toehold switch trigger RNA, according to some embodiments. FIG. 11B is a schematic showing a construct comprising an aptamer having a disjointed RNA thermometer (RNAT) and toehold switch components, according to some embodiments. FIG. 11C is a schematic showing activation of a construct comprising an aptamer having a disjointed RNAthermometer (RNAT) and toehold switch components, according to some embodiments. The aptamer contains both an RNA thermometer component and a Toehold switch component, encoded by a Chemically Induced Promoter [I], Within these components are an IRES and AUG Translational Start Sequence to initiate transcription of the downstream Output Transcription Factor (promoting Gene-of-Interest, which here is aIL-6), as well as a RNA Binding Protein Site to complex the aptamer with a ferritin-RBP fusion protein. Hairpin loop structures from the 2 components may inhibit proper access to these sites necessary for translation of this RNA or act to pause / inhibit bound ribosomes. Thus, successful expression of the Gene-of-Interest requires full unfolding, thus both EM-radiation [II] to heat up the adjacent RNA thermometer and the IL-6 / NF-kB-promoted [III] Toehold trigger sequence to synthesize the Output TF. Following unfolded aptamer expression, a 2A site will release Output TF to promote aIL-6 expression, as well as transcription factor X that promotes the aptamer synthesis. Thus, a positive feedback-loop is generated to allow for an increasing theoretical yield of aIL-6 that is able to be perfectly controlled and stopped with and without EM radiation. Here, the aptamer has disjointed RNA thermometer and toehold switch components.

[0157] The placement of the RNA thermometer and Toehold switch, as well as the respective IRES and AUG sites within them, is evaluated via testing.

[0158] FIG. 12A-D is a series of schematics showing a construct comprising an aptamer having unified RNA thermometer and toehold switch components, according to some embodiments. FIG. 12A is a schematic showing activation of a construct comprising an aptamer having an unified RNA thermometer (RNAT) and toehold switch components, according to some embodiments. FIG. 12B is a schematic showing activation of a construct comprising an aptamer having an unified RNA thermometer (RNAT) and toehold switch components, according to some embodiments. FIG. 12C is a schematic showing a construct for expressing a toehold switch trigger RNA, according to some embodiments. FIG. 12D is a schematic showing a construct comprising an aptamer having an unified RNA thermometer (RNAT) and toehold switch components, according to some embodiments. The aptamer contains both an RNA thermometer component and a Toehold switch component, encoded by a Chemically Induced Promoter [I], Within these components are an IRES and AUG Translational Start Sequence to initiate transcription of the downstream Output TranscriptionFactor (promoting Gene-of-Interest, which here is aIL-6), as well as a RNA Binding Protein Site to complex the aptamer with a ferritin-RBP fusion protein. Hairpin loop structures from the 2 components may inhibit proper access to these sites necessary for translation of this RNA or act to pause / inhibit bound ribosomes. Thus, successful expression of the Gene-of-Interest requires full unfolding, thus both EM-radiation [II] to heat up the adjacent RNA thermometer and the IL-6 / NF-kB-promoted [III] Toehold trigger sequence to synthesize the Output TF. Following unfolded aptamer expression, a 2 A site will release Output TF to promote aIL-6 expression, as well as transcription factor X that promotes the aptamer synthesis. Thus, a positive feedback-loop is generated to allow for an increasing theoretical yield of aIL-6 that is able to be perfectly controlled and stopped with and without EM radiation. Here, the aptamer has unified RNA thermometer and toehold switch components.

[0159] FIG. 13A-D is a series of schematics showing sequential assembly and activation of a construct with a disjointed aptamer. FIG. 13A is a schematic depicting Ferritin- RNA-Binding Protein (RBP) and aptamer synthesis. FIG. 13B is a schematic showing Ferritin- RNA-Binding Protein (RBP) and aptamer coupling. FIG. 13C is a pair of schematics showing toehold switch activation (top) and RNA thermometer (RNAT) activation (bottom). FIG. 13D is a schematic showing RNA thermometer (RNAT) - toehold switch activation.Aptamer Concept Development and Optimization:

[0160] An example of consolidation of RNA-based sensors (i.e., RNA thermometer and toehold switch) is described in this non-limiting example and gives scalability to the technology (compared to protein-based systems), allowing easier development and tuning of the system, whether through computational methods or directed evolution.

[0161] Computational methods: Software tools for the creation, screening, and folding of RNA sequence and riboswitches were developed along with a custom computer program allowing for the design of thermosensitive RNAs and toehold-containing RNA structures and their in silico evaluation.

[0162] Repositories of software and parts of the project can be found at Synthetic Biology Open Language (SBOL) - SBOL resource and application database, iGEM PartsRegistry - iGEM-based database of available biobricks, and SynBioHub - Larger BioBrick database.

[0163] Directed evolution: A directed evolution experiment may be run using a curated aptamer library for mass-screening and optimization. In the experiment, a library of diverse, curated aptamers is generated. The aptamers are unfolded at 37°C. Site-directed RNase is added, cleaving the aptamers. The RNase is then inhibited (RNase-Out) before a solution containing the aptamers is aliquoted into separate tubes. The tubes are then each placed in a thermocycler at different temperatures; If assessing a combined RNA Thermometer-Toehold Switch, a Toehold Switch Trigger sequence is added. Maintaining the given temperature, a reverse transcriptase reaction is ten performed, and a non-specific RNase is added to remove folded hair pins of a RNA Thermometer or toehold switch, which will not form cDNA. PCR is then performed on the cDNA. Reverse transcribed aptamers are then sequenced at different temperatures. This indicates the thermostability of each aptamer and allows selection of an aptamer(s) that unfolds at or above a desired temp. This process may inform a new direction in aptamer library synthesis, in which the process can be repeated.IL-6 Effector:

[0164] A variety of proteins may function as IL-6 effectors and are described in this non-limiting example. One of considerable interest is a mutant variant of a soluble IL-6 receptor (mut. Soluble gp80; BBa K2760003) that antagonizes and sequesters the molecule, in particular, IL-6 molecules involved in the pro-inflammatory trans-acting pathway. More research is required to assess feasibility of this approach, however its simplicity and similarity to native soluble proteins increases its desirability.

[0165] A secondary approach is to secrete pre-approved IL-6 targeting antibodies, useful from a efficacy and regulatory perspective. One example includes siltuximab, which targets IL-6 directly. Other antibodies (e.g., tocilizumab, sarilumab) that target the IL-6 receptor are also explored.Host Organisms:

[0166] Based on the end-goal of immunotherapeutic applications, functional hosts used during development are mammalian cell lines as described in this non-limiting example.This ensures proper membrane insertion and aptamer optimization in an environment comparable to an in vivo one. Current cell lines may include HEK293 (common eukaryotic cell line) or Jurkat (immune cell line).Plasmid Construction

[0167] A finalized system may be housed on 1-2 plasmids as described in this nonlimiting example. A single plasmid system has advantages in reducing the number of components to transfect. A dual plasmid system is desirable in the modularity it may provide. In other words, one plasmid may be dedicated to EM-reception and the logic operations, while another may be purposed for compound-specific actions: sensing (here, IL-6) and antagonization (here, mut. sgp80). This allows for quick swapping of the sensed entity of interest to other (or multiple) interleukins, chemokines, etc. as long as they have associated transcription factors and / or intracellular mRNA expression. It also permits various antagonists, such as anti -IL-6, anti-IL-10, cyclosporin A (polyketide immunosuppressant), etc.

[0168] This swapability also allows the system to convert from an immuno- inhibitory (anti-autoimmune) state to an immuno-stimulatory state that may be utilized as a localized cancer immunotherapy. Thus, the disclosure herein provides value in producing locally-activated CAR-T cells, for example, that not only minimizes off-target effects, but directs function and expansion of the therapeutic at the target site.

[0169] FIG. 14 is an illustration showing some embodiments of a description of a plasmid.

[0170] FIG. 15 is a schematic showing the plasmid layout within the LEMII system architecture.

[0171] As the understanding of the immune system increases, its role in the modern understanding and manipulation of human health has as well. Localized control of these cells lends great benefit to curbing autoimmune conditions, infectious disease, and cancer. Disclosed herein is a system for, among other things, localized immune down-regulation, particularly targeted towards proinflammatory IL-6 that can play a role in rheumatoid arthritis, diabetes, organ transplantation, lupus, and an array of other autoimmune conditions. Utilizing an aptamer structure containing a ferritin-associated RNA thermometer and IL-6 / NF-KB sensitive toehold switch, anti-IL-6 can be produced via integrated feedback loop to sequesterIL-6 upon electromagnetic stimulation. This localized immunosuppression technology is also beneficial in immunostimulation, where it may produce localized CAR-T cells targeting cancer directly.Example 2:Nanoparticle Selection and Synthesis

[0172] Gold-coated Iron Oxide magnetic nanoparticles (AuMNPs, spherical with diameter 20 nm) were conjugated to the 3’ end of a 20 nucleotide DNA oligomer via thiol chemistry, yielding a surface density of 439.6 oligos / AuMNP. The oligomer was selected for a lack of significant secondary structure across relevant temperatures. Therefore, the oligomer stably bound to a RNA nanostructure of interest with a high melting point.RNA Nanostructure Design

[0173] Cloned DNA (gene fragment or plasmid) and its associated RNA nanostructure (RNS) products were designed first by hand and then computationally to enable multi-state structural changes activated by AuMNP binding and magnetic induction. RNA structures differed across domains of life, with prokaryotic and eukaryotic RNA nanostructures employing different conserved and non-conserved motifs for efficient transcription, translation, and secondary structure.

[0174] FIG. 16 is a graph depicting expression and luminescence from a prokaryotic construct according to some embodiments disclosed herein under no heat, heat shock, and alternating magnetic field induction.

[0175] FIG. 21 is an image of an in silico-designed construct according to some embodiments disclosed herein.

[0176] Prokaryotic RNS designs (FIG. 16) featured a 5’ nanoparticle- oligonucleotide binding sequence directly upstream of an energetically susceptible nucleotide tract obstructing the Shine-Dalgarno sequence and optionally start codon for a downstream expression product, here, either NanoLuciferase or mScarlet. The gene fragments were ended with a 3x stop-codon and high-efficiency RNA pol terminator sequence (i.e., tZ). The eukaryotic RNS designs varied more widely to circumnavigate 5’ capping and 3’ polyadenylation requirements. One structure utilized a Cricket paralysis virus (CrPV) intergenic-region internal ribosome entry site (IGR IRES) (see FIG. 16, and FIG. 21)engineered with multiple internal binding configurations, allowing for wild-type folding and occlusive binding. Multiple complementary sites were engineered inside the 5 ’-localized CrPV expressing a central gene product (i.e., NanoLuciferase or mGreenLantern), 3x stop codon, and capped with a 3 ’ segment exclusively complementary to the engineered CrPV site and to the nanoparticle-conjugated oligonucleotide. The 3’ occlusion segment (composed of an initial lOmer CrPV-IRES-complement, a 10-30mer linker, and a second 10 / 15 / 30 / 45mer CrPV- IRES-complement) bound two sites within the CrPV IRES and distanced by linker length. The RNS folds into a default-off, occluded state inhibiting expression, which is reversibly countered by AMF stimulation of the conjugated AuMNP antennae (hence, altering RNS secondary structure and allowing enzymatic activities such as translation). Depending on the linker length, the CrPV IRES’s secondary structure was altered to inhibit ribosomal binding and translational initiation. The alterations included the ribosomal binding structure, Kozak consensus sequences, and start codons (AUG, GCT). Alternative structures featured 5’ nanoparticle binding and CrPV-IRES-occluding sequences, as well as variants without the use of traditional Kozak consensus sequences. Other variants included built-in product tags for protease-based signal initiation or constitutive degradation (i.e., PEST sequences).AMF Induction

[0177] The output coil of the AMF-generator was single-turn with a diameter of 28mm and thickness corresponding to a single layer of 2oz copper on a 0.8mm thickness FR4 printed circuit board. The coil’s impedance was matched to 50 Ohm using surface mount inductors, resistors, and capacitors. The impedance-matched coil circuit was driven by a MiniCircuits ZFL-1000VHB+ amplifier. The amplifier input signal was generated by a SynthUSB3. Output field flux density was measured with a Beehive Electronics 100B field probe and a spectrum analyzer.AMF Induction on Prokaryotic / Eukaryotic Samples

[0178] Plasmids and gene fragments were either abiotically synthesized (Twist Biosciences, South San Francisco) or assembled into plasmids. Plasmids were optionally linearized into fragments ending with the expression target ORF. These plasmids or gene fragments were resuspended to a concentration of 100 ng / pL in Tris-EDTA buffer andsubsequently placed on ice. Prokaryotic and Eukaryotic cells or cell-free lysate were thawed from storage and put on ice.

[0179] FIG. 16 is a graph depicting expression and luminescence from a prokaryotic construct according to some embodiments disclosed herein under no heat, heat shock, and alternating magnetic field induction.

[0180] FIG. 17 is a graph depicting expression and luminescence from an eukaryotic construct according to some embodiments disclosed herein under alternating magnetic field induction.

[0181] FIG. 22 is an image of an in silico-designed construct in the “Off’ configuration according to some embodiments disclosed herein.

[0182] FIG. 23 is a schematic showing an in-silico designed variant in the “On” configuration according to some embodiments disclosed herein.

[0183] FIG. 16 shows data generated using a prokaryotic RNA-AuMNP induction system, while FIG. 17 and FIG. 22-23 show data generated using a eukaryotic RNA-AuMNP induction system. For HeLa cell-free lysates, the lysate, accessory proteins, reaction mixture, and molecular-grade water were thawed and placed on ice. Hela Lysate, Accessory Protein Mix, Reaction Mix, Nuclease- free Water, and 3’-SH Oligo-X-Linked AuMNPs (2 nM) were added into a 1.5 mL LoBind microcentrifuge tube, in the specified order, with thorough mixing throughout to make a Cell-Free Master Mix (CFMM). CFMM was aliquoted into labeled 0.2mL tubes and mixed with the distinct DNA templates (100 ng / pL). Following this, the CFMM with template samples were subsequently split into lOpL aliquots within a 0.2mL tube for each alternating-magnetic field (AMF) treatment group with replicates (n=3) for each.

[0184] Samples were incubated for 60 minutes at 30°C as a means to generate the plasmid / gene fragment’s T7-promoted RNA fragment. Following this, paired AMF and non- AMF groups were placed into the AMF-generating apparatus or in a separate enclosure without detectable AMF strength for 30 minutes at an ambient temperature of 25°C. The AMF generator was set to 185.4 MHz, and the output flux density was measured to be 17.97 pT. Following induction time, both AMF and non- AMF samples were placed into an incubator for 30 minutes at 30°C to allow for sustained expression of activated RNA structures into the quantifiable product (NanoLuciferase). Following expression, the sample was stored at 4°C for at least 30 minutes to quench enzymatic activity and removed prior to luminescencereadout. 8pL of each lOpL IVT sample was added into 42 pL of deionized H2O across the wells of a glass-bottom white-wall luminescence. 50pL of NanoLuciferase substrate (furimazine, Nano-Gio® Luciferase Assay System; Promega, Madison) was added to the plate in a multichannel format and ran on the BioTek Cytation5 Multimodal Plate reader 3 minutes post-substrate addition. A kinetic luminescence readout was acquired from below every 2 minutes using the machine’s luminescence fiber (1 second integration time). Raw RLU values were blanked versus water standard, and then the comparison between AMF and non-AMF groups was conducted. Additionally, the ratio of expression downregulation from the RNS’s intramolecular occlusion sequence was assessed.RNS Optimization:

[0185] In addition to computational methods for structure optimization, multiplexed RNA expression panels (Table 1) assessed RNS energetic-bistability (or multistability) to find optimized occlusion secondary structures, CrPV binding sites, 573’ occlusion, nanoparticle sequence orientation, translational recruitment domains inclusion, and multivalency of occlusion sequence(s). HeLa CFMM was prepared according to the protocol outlined above. The sample was then split into lOpL aliquots within a 0.2mL tube for each heat shock condition.

[0186] Samples were incubated at 30°C for 60 minutes to generate an adequate concentration of RNSs. Then, samples were incubated for 2 minutes at assigned heat shock temperatures (30°C, 42°C, 52°C) and then left to continue expression for 13 minutes at 30°C. This heat shock protocol was repeated three times for an aggregate of 45 minutes of induction and translation time. The quantifiable product (NanoLuciferase) was quantified using a plate reader assay. Following expression, the sample was stored at 4°C for at least 30 minutes to quench enzymatic activity and removed prior to luminescence readout. The IVT NanoLuciferase sample dilution and plate readout were prepared according to the protocol outlined above. Raw RLU values were blanked, and then the comparison between heat shocked and non-heat shocked groups could be conducted. Additionally, the ratio of expression downregulation from the RNS’s intramolecular occlusion sequence could be assessed. Additionally, prokaryotic RNS were trialed inside E. coli KI 2 using the aforementioned heat shock protocol and read-out methodologies.Table 1. Eukaryotic Thermosensitive IRES Switch Panel

[0187] The disclosed technology includes, but is not limited to: A construct for expression or regulation of a target molecule, the construct comprising: a thermosensitive element, and a signal transducing element; wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element; and wherein the conformational change in the thermosensitive element allows expression or regulation of a target molecule. In this construct, the thermosensitive element can comprise a nucleic acid. In this construct, the nucleic acid can be RNA or DNA. In this construct, the thermosensitive element can comprise a protein. In this construct, the thermosensitive element can comprise one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this construct, the thermosensitive element can comprise one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site(IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In this construct, the signal transducing element can comprise a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In this construct, the signal transducing element can comprise a ferritin nanoparticle. In this construct, the signal transducing element can comprise an oxidized nanoparticle. In this construct, the oxidized nanoparticle can be an iron oxide nanoparticle. In this construct, the signal can comprise a tissue penetrating signal. In this construct, wherein the signal can comprise a wireless signal. In this construct, the signal can comprise alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In this construct, the signal can comprise an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In this construct, the signal can comprise an alternating magnetic field at a frequency of up to about 250 MHz. In this construct, the signal can comprise an alternating magnetic field at a field strength of up to about 100 kA / m. In this construct, the signal can comprise an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In this construct, transduction of a signal to the thermosensitive element can result in ballistic heat transfer from the signal transducing element to the thermosensitive element. In this construct, transduction of a signal to the thermosensitive element can result in an increase in the temperature of the thermosensitive element. In this construct, the temperature can increase by between about 0.1 °C and 35 °C. In this construct, transduction of a signal to the thermosensitive element can result in an increase in the free energy (AG) of the thermosensitive element. In this construct, the free energy (AG) can increase by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In this construct, the free energy (AG) can increase by between about 1 Kcal / mol and about 15 Kcal / mol. In this construct, the conformational change in the thermosensitive element can obstruct and / or de-obstruct one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independenttranslation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this construct, the temperature of the thermosensitive element can decrease following cessation of the signal. This construct can further comprise a linker. In this construct, regulation of a target molecule can comprise obstruction and / or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In this construct, regulation of a target molecule can comprise obstruction and / or de-obstruction of one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this construct, regulation of a target molecule can comprise obstruction and / or de-obstruction of one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof.

[0188] Also disclosed is a construct for programmed conformational change, the construct comprising: a thermosensitive element, and a signal transducing element; wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; and wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element. In this construct, the conformational change in the thermosensitive element can obstructs one or more genetic elements. In this construct, the conformational can change in the thermosensitive element de-obstructs one or more genetic elements. In this construct, the thermosensitive element can comprise a nucleic acid, and thenucleic acid can be RNA or DNA. In this construct, the thermosensitive element can comprise a protein. In this construct, the thermosensitive element can comprise one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered capindependent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this construct, the thermosensitive element can comprise one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), capindependent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In this construct, the signal transducing element can comprise a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In this construct, the signal transducing element comprises a ferritin nanoparticle. In this construct, the signal transducing element can comprise an oxidized nanoparticle. In this construct, the oxidized nanoparticle can be an iron oxide nanoparticle. In this construct, the signal can comprise a tissue penetrating signal. In this construct, the signal can comprise a wireless signal. In this construct, the signal can comprise alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In this construct, the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In this construct, the signal can comprise an alternating magnetic field at a frequency of up to about 250 MHz. In this construct, the signal can comprise an alternating magnetic field at a field strength of up to about 100 kA / m. In this construct, the signal can comprise an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In this construct, transduction of a signal to the thermosensitive element can result in ballistic heat transfer fromthe signal transducing element to the thermosensitive element. In this construct, transduction of a signal to the thermosensitive element can results in an increase in the temperature of the thermosensitive element. In this construct, the temperature can increase by between about 0.1 °C and 35 °C. In this construct, transduction of a signal to the thermosensitive element can results in an increase in the free energy (AG) of the thermosensitive element. In this construct, the free energy (AG) can increase by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In this construct, the free energy (AG) can increase by between about 1 Kcal / mol and about 15 Kcal / mol. In this construct, the conformational change in the thermosensitive element can obstruct and / or de-obstruct one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpinloop structure, and any combination thereof. In this construct, obstruction and / or deobstruction of one or more genetic elements can alter expression and / or regulation of one or more target molecules. In this construct, the conformational change in the thermosensitive element can obstruct and / or de-obstruct one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In this construct, obstruction and / or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element can alter expression and / or regulation of one or more target molecules. In this construct, the conformational change in the thermosensitive element can obstruct and / or de-obstruct one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), capindependent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In this construct, obstruction and / or deobstruction of one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor(TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof, can alter expression and / or regulation of one or more target molecules. In this construct, the temperature of the thermosensitive element can decrease following cessation of the signal. This construct can further comprising a linker.

[0189] Also disclosed is a gene expression construct comprising: a thermosensitive nucleic acid, and a magnetically-susceptible nanoparticle, wherein the thermosensitive nucleic acid is configured to change confirmations upon transduction of a signal from the magnetically-susceptible nanoparticle to the thermosensitive nucleic acid. In this construct, the thermosensitive element can comprise a nucleic acid. In this construct, the nucleic acid can be RNA or DNA. In this construct, the thermosensitive element can comprise a protein. In this construct, the thermosensitive element can comprise one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this construct, the thermosensitive element can comprise one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or anycombination thereof. In this construct, the signal transducing element can comprise a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In this construct, the signal transducing element can comprise a ferritin nanoparticle. In this construct, the signal transducing element can comprise an oxidized nanoparticle. In this construct, the oxidized nanoparticle can be an iron oxide nanoparticle. In this construct, the signal can comprise a tissue penetrating signal. In this construct, the signal can comprise a wireless signal, and the signal can comprise alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In this construct, the signal can comprise an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In this construct, the signal can comprise an alternating magnetic field at a frequency of up to about 250 MHz. In this construct, the signal can comprise an alternating magnetic field at a field strength of up to about 100 kA / m. In this construct, the signal can comprise an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In this construct, transduction of a signal to the thermosensitive element can result in ballistic heat transfer from the signal transducing element to the thermosensitive element. In this construct, transduction of a signal to the thermosensitive element can result in an increase in the temperature of the thermosensitive element. In this construct, the temperature can increase by between about 0.1 °C and 35 °C. In this construct, transduction of a signal to the thermosensitive element can result in an increase in the free energy (AG) of the thermosensitive element. In this construct, the free energy (AG) can increase by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In this construct, the free energy (AG) can increase by between about 1 Kcal / mol and about 15 Kcal / mol. In this construct, the conformational change in the thermosensitive element obstructs and / or deobstructs one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this construct, obstruction and / or de-obstruction of one or more genetic elements can alter expression and / or regulation of one or more genes. Inthis construct, the conformational change in the thermosensitive element can obstruct and / or de-obstruct one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In this construct, obstruction and / or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element, can alter expression and / or regulation of one or more genes. In this construct, the conformational change in the thermosensitive element can obstruct and / or de-obstruct one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In this construct, obstruction and / or de-obstruction of one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In this construct, the temperature of the thermosensitive element can decrease following cessation of the signal. This construct can further comprise a linker.

[0190] Also disclosed is a method of expressing or regulating a target molecule, the method comprising: administering a construct for expression or regulation of a target molecule to a subject, the construct comprising: a thermosensitive element, and a signal transducing element; and applying a signal to the signal transducing element. In this method, the signal to the thermosensitive element can cause a conformational change in the thermosensitive element. In this method, the conformational change in the thermosensitive element can alter expression and / or regulation of a target molecule. In this method, altered expression and / or regulation of a target molecules can activate and / or deactivate one or more molecularprocesses. In this method, the molecular process can comprise a spatial and / or temporal: upregulation / downregulation of gene expression and / or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof. In this method, the thermosensitive element can comprise a nucleic acid. In this method, the nucleic acid can be RNA or DNA. In this method, the thermosensitive element can comprise a protein. In this method, the thermosensitive element comprises one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this method, the thermosensitive element can comprise one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly- A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loop structure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In this method, the signal transducing element can comprise a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, and / or a protein complex, or any combination thereof. In this method, the signal transducing element can comprise a ferritin nanoparticle. In this method, the signal transducing element can comprise an oxidized nanoparticle. In this method, the oxidized nanoparticle can be an iron oxide nanoparticle. In this method, the signal can comprise a tissue penetrating signal. In this method, the signal can comprise a wireless signal. In this method, the signal can comprise alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof. In this method, the signal can comprise an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz. In this method, the signal can comprise an alternating magnetic field at a frequency of up to about 250 MHz.In this method, the signal can comprise an alternating magnetic field at a field strength of up to about 100 kA / m. In this method, the signal can comprise an alternating magnetic field at a field strength of about 10 kA / m to about 20 kA / m. In this method, transduction of a signal to the thermosensitive element can result in ballistic heat transfer from the signal transducing element to the thermosensitive element. In this method, transduction of a signal to the thermosensitive element can result in an increase in the temperature of the thermosensitive element. In this method, the temperature can increase by between about 0.1 °C and 35 °C. In this method, transduction of a signal to the thermosensitive element can results in an increase in the free energy (AG) of the thermosensitive element. In this method, the free energy (AG) can increase by between about 0.01 Kcal / mol and about 1,000 Kcal / mol. In this method, the free energy (AG) can increase by between about 1 Kcal / mol and about 15 Kcal / mol. In this method, the conformational change in the thermosensitive element can obstruct and / or deobstruct one or more genetic elements selected from: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof. In this method, obstruction and / or de-obstruction of one or more genetic elements can alter expression and / or regulation of one or more genes. In this method, the conformational change in the thermosensitive element can obstruct and / or deobstruct one or more DNA, RNA, and / or protein binding sites on the thermosensitive element. In this method, obstruction and / or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element, can alter expression and / or regulation of one or more genes. In this method, the conformational change in the thermosensitive element can obstruct and / or de-obstruct one or more Luciferase mRNA, chromoprotein mRNA, Transcription Factor (TF) mRNA, promoters, enhancers, repressors, silencers, insulators, ribosome binding sites, 5' cap, ribosomal translation start codon, 3' termini, 3' poly-A tail, internal ribosomal entry site (IRES), cap-independent translation enhancer (CITE), transcription factor binding sites, translation initiation factor (IF) binding site, eukaryotic initiation factor (elF) binding site, Shine-Dalgarno sequence, Kozak sequence, a hairpin-loopstructure, a toehold switch, a protein coding sequence or functional RNA sequence, for example, a catalytic RNA or ribozyme, single guide RNA (sgRNA), and / or any combination thereof. In this method, obstruction and / or de-obstruction of one or more Luciferase mRNA, chromopr...

Claims

WHAT IS CLAIMED IS:

1. A construct for expression or regulation of a target molecule, the construct comprising: a thermosensitive element, and a signal transducing element; wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element; and wherein the conformational change in the thermosensitive element allows expression or regulation of a target molecule.

2. A construct for programmed conformational change, the construct comprising: a thermosensitive element, and a signal transducing element; wherein a signal applied to the signal transducing element is transduced to the thermosensitive element; and wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element.

3. The construct of claim 1 or claim 2, wherein the thermosensitive element comprises a nucleic acid.

4. The construct of claim 3, wherein the nucleic acid is RNA or DNA.

5. The construct of any one of claims 2-4, wherein the conformational change in the thermosensitive element alters expression or regulation of one or more target molecules.

6. The construct of claim 1 or claim 2, wherein the thermosensitive element comprises a protein.

7. The construct of any one of claims 1-6, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translationinitiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop8. The construct of any one of claims 1-7, wherein the signal transducing element is selected from the group comprising a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, a protein complex, and any combination thereof.

9. The construct of any one of claims 1-7, wherein the signal transducing element comprises a ferritin nanoparticle.

10. The construct of any one of claims 17, wherein the signal transducing element comprises an oxidized nanoparticle.

11. The construct of claim 10, wherein the oxidized nanoparticle is an iron oxide nanoparticle.

12. A gene expression construct comprising: a thermosensitive nucleic acid, and a magnetically-susceptible nanoparticle; wherein the thermosensitive nucleic acid is configured to change confirmations upon transduction of a signal from the magnetically-susceptible nanoparticle to the thermosensitive nucleic acid.

13. The construct of any one of claims 1-12, wherein the signal comprises a tissue penetrating signal.

14. The construct of any one of claims 1-12, wherein the signal comprises a wireless signal.

15. The construct of any one of claims 1-14, wherein the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof.

16. The construct of any one of claims 1-14, wherein the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz.

17. The construct of any one of claims 1-14, wherein the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m.

18. The construct of any one of claims 1-17, wherein transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element.

19. The construct of any one of claims 1-17, wherein transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element.

20. The construct of claim 21, wherein the temperature increases by between about 0.1 °C and 35 °C.

21. The construct of any one of claims 1-17, wherein transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element.

22. The construct of claim 23, wherein the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol.

23. The construct of any one of claims 1-22, wherein the conformational change in the thermosensitive element obstructs one or more genetic elements.

24. The construct of 1 -22, wherein the conformational change in the thermosensitive element de-obstructs one or more genetic elements.

25. The construct of any one of claims 1-24, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered capindependent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.

26. The construct of any one of claims 1-25, wherein the temperature of the thermosensitive element decreases following cessation of the signal.

27. The construct of any one of claims 1 -26, further comprising a linker.

28. The construct of any one of claims 1-27, wherein regulation of a target molecule comprises obstruction or de-obstruction of one or more DNA, RNA, and / or protein binding sites on the thermosensitive element.

29. The construct of claim 28, wherein obstruction or de-obstruction of one or more DNA, RNA, or protein binding sites on the thermosensitive element alters expression or regulation of one or more target molecules.

30. The construct of any one of claims 1 or 5-27, wherein regulation of a target molecule comprises obstruction or de-obstruction of one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered capindependent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.

31. The construct of any one of claims 23-30, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.

32. The construct of claim 31, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-1,000 fold.

33. The construct of claim 31, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100,00%.

34. The construct of any one of claims 23-30, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.

35. The construct of claim 34, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-1,000 fold.

36. The construct of claim 34, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100,00%.

37. A method of expressing or regulating a target molecule, the method comprising: administering a construct for expression or regulation of a target molecule to a subject, the construct comprising: a thermosensitive element, and a signal transducing element; and applying a signal to the signal transducing element.

38. The method of claim 37, wherein transduction of the signal to the thermosensitive element causes a conformational change in the thermosensitive element.

39. A method of programed conformational change, the method comprising: applying a signal to a signal transducing element; wherein transduction of the signal to a thermosensitive element causes a conformational change in the thermosensitive element.

40. The method of any one of claims 37-39, wherein the conformational change in the thermosensitive element allows expression or regulation of a target molecule.

41. The method of any one of claims 37-40, further comprising monitoring expression or regulation of the target molecule.

42. The method of claim 40, wherein altered expression or regulation of the target molecule indicates ballistic energy transfer from the signal transducing element to the thermosensitive element.

43. The method of any one of claims 41-42 wherein altered expression or regulation of a target molecules activates or deactivates one or more molecular processes.

44. The method of claim 43, wherein the molecular process comprises a spatial or temporal: upregulation / downregulation of gene expression or metabolic pathways, localization of cells within a body, immunological stimulation of target regions, immunosuppression of target regions, or any combination thereof45. The method of any one of claims 37-44, wherein the thermosensitive element comprises a nucleic acid.

46. The method of claim 45, wherein the nucleic acid is RNA or DNA.

47. The method of any one of claims 37-46, wherein the thermosensitive element comprises a protein.

48. The method of any one of claims 37-46, wherein the thermosensitive element comprises one or more genetic elements selected from the group comprising: sterically- hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered cap-independent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translationinitiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.

49. The method of any one of claims 37-48, wherein the signal transducing element is selected from the group comprising: a nanoparticle, magnetic nanoparticle, a nucleic acid nanostructure, a protein, a protein complex, and any combination thereof.

50. The method of any one of claims 37-48, wherein the signal transducing element comprises a ferritin nanoparticle.

51. The method of any one of claims 37-48, wherein the signal transducing element comprises an oxidized nanoparticle.

52. The method of claim 51, wherein the oxidized nanoparticle is an iron oxide nanoparticle.

53. The method of any one of claims 37-52, wherein the signal comprises a tissue penetrating signal.

54. The method of any one of claims 37-52, wherein the signal comprises a wireless signal.

55. The method of any one of claims 37-52, wherein the signal comprises alternating magnetic fields, magnetic field gradients, electromagnetic stimulation, or any combination thereof.

56. The method of any one of claims 37-52, wherein the signal comprises an alternating magnetic field at a frequency of between about 0.1 MHz and about 1,000 MHz.

57. The method of any one of claims 37-52, wherein the signal comprises an alternating magnetic field at a field strength of up to about 100 kA / m.

58. The method of any one of claims 37-57, wherein transduction of a signal to the thermosensitive element results in ballistic heat transfer from the signal transducing element to the thermosensitive element.

59. The method of any one of claims 37-57, wherein transduction of a signal to the thermosensitive element results in an increase in the temperature of the thermosensitive element.

60. The method of claim 59, wherein the temperature increases by between about 0.1C and 35 °C.

61. The method of any one of claims 37-57, wherein transduction of a signal to the thermosensitive element results in an increase in the free energy (AG) of the thermosensitive element.

62. The method of claim 61, wherein the free energy (AG) increases by between about 0.01 Kcal / mol and about 1,000 Kcal / mol.

63. The method of any one of claims 37-62, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: sterically-hindered ribosome binding sites, sterically hindered 5' cap, ribosomal translation start codon, sterically hindered 3' termini, sterically hindered 3' poly- A tail, sterically hindered internal ribosomal entry site (IRES), sterically hindered capindependent translation enhancers (CITEs), sterically hindered transcription factor binding sites, sterically hindered translation initiation factor (IF) binding sites, sterically hindered eukaryotic initiation factor (elF) binding sites, and a hairpin-loop structure, and any combination thereof.

64. The method of any one of claims 37-62, wherein the conformational change in the thermosensitive element obstructs or de-obstructs one or more genetic elements selected from the group comprising: DNA, RNA, or protein binding sites on the thermosensitive element.

65. The method of any one of claims 63-64, wherein obstruction or de-obstruction of one or more genetic elements alters expression or regulation of one or more genes.

66. The method of any one of claims 63-64, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules.

67. The construct of claim 66, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-1,000 fold.

68. The construct of claim 66, wherein obstruction or de-obstruction of one or more genetic elements increases expression of one or more target molecules by about 1-100,00%.

69. The method of any one of claims 63-64, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules.

70. The method of claim 69, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-1,000 fold.

71. The construct of claim 69, wherein obstruction or de-obstruction of one or more genetic elements decreases expression of one or more target molecules by about 1-100,00%.

72. The method of any one of claims 37-71, wherein the temperature of the thermosensitive element decreases following cessation of the signal.

Images