1-17. (canceled)
18. A storage apparatus comprising:
a multi-compartment bag formed of a flexible material having an upper portion and a lower portion, the upper portion comprising an upper first compartment and an upper second compartment, the lower portion comprising a lower first compartment and a lower second compartment, the multi-compartment bag having one or more seams and one or more resealable opening edges, the multi-compartment bag having a front surface, a back surface, and a generally rectangular peripheral edge defined by a top edge, a bottom edge, and opposing side edges, the one or more seams including at least one tearable seam, the tearable seam including a perforated seam positioned between a first solid seam and a second solid seam, the perforated seam configured to physically separate one of the compartments from the multi-compartment bag.
19. The storage apparatus of claim 18, further comprising:
one or more chambers separating the upper first compartment and the upper second compartment from the lower first compartment and the lower second compartment; and
one or more chamber closures removably attached to each of the one or more chambers.
20. The storage apparatus of claim 19, wherein the one or more chamber closures are selected from a group consisting of a twist-off cap and a pop-off cap.
21. The storage apparatus of claim 19, wherein the one or more chambers are smaller than each compartment of the multi-compartment bag.
22. The storage apparatus of claim 18, wherein the perforated seam is positioned along a horizontal axis, a vertical axis, or at an angle.
23. The storage apparatus of claim 18, further comprising:
one or more resealing elements selected from a group consisting of a zippered closure, a press lock, a magnetic closure, a snap closure, and a heat seal,
wherein each resealable opening edge is sealed and unsealed using at least one of the resealing elements.
24. The storage apparatus of claim 18, wherein the flexible material is selected from a group consisting of hemp, cotton, cloth, burlap, mesh, plastic, and a laminated material.
25. The storage apparatus of claim 18, wherein the flexible material is water proof or moisture proof.
26. The storage apparatus of claim 18, further comprising:
a first handle comprising a first hole positioned on the front surface; and
a second handle comprising a second hole positioned on the back surface,
wherein the first hole and the second hole are substantially aligned with each other.
27. The storage apparatus of claim 18, further comprising:
a first handle attached to the front surface at a front first position and a front second position; and
a second handle attached to the back surface at a back first position and a back second position;
wherein the front first position and the back first position are substantially aligned with each other, and
wherein the front second position and the back second position are substantially aligned with each other.
28. The storage apparatus of claim 18, wherein the upper first compartment and the upper second compartment share a first resealable opening edge along the top edge of the multi-compartment bag, and
wherein the lower first compartment and the lower second compartment share a second resealable opening edge along the bottom edge of the multi-compartment bag.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-122. (canceled)
123. A signal-activatable polynucleotide construct for enzyme-assisted molecular delivery, the construct comprising:
a targeting domain and
a sensor domain covalently bound to the targeting domain, the sensor domain comprising:
a signal detection region complementary to at least one signal polynucleotide,
a first chimeric sequence comprising at least one RNA region,
a second chimeric sequence comprising a DNA region complementary to an RNA region of the at least one RNA regions of the first chimeric sequence, and
a masking segment complementary to the first chimeric sequence;
wherein the sensor domain is configured such that:
in absence of the signal polynucleotide,
the masking segment hybridizes with the first chimeric sequence,
the DNA region of the second chimeric sequence is in a configuration not processable by RNase H, and
the signal detection region is presented for binding to the signal polynucleotide; and
in presence of the signal polynucleotide,
the signal detecting region hybridizes with the signal polynucleotide,
the masking segment is displaced from the first chimeric sequence, and
the DNA region of the second chimeric sequence hybridizes with the complementary RNA region of the at least RNA region of the first chimeric sequence to provide an RNase H binding site presented for binding to RNase H, and
the sensor domain is configured to allow release of the targeting domain from the sensor domain upon cleavage of the RNase H binding site by the RNase H.
124. The signal activatable construct of claim 123, wherein the second chimeric sequence and the targeting domain are located at opposite sides of the first chimeric sequence.
125. The signal activatable construct of claim 123, wherein the inactive conformation the DNA region of the second chimeric sequence hybridizes with an RNA-DNA region of the second chimeric sequence.
126. The signal activatable construct of claim 123, wherein the complementary binding of the at least one signal polynucleotide to the signal detection region results in a duplex polynucleotide having approximately 20 consecutive base pairs.
127. The signal-activated polynucleotide construct of claim 123, wherein the construct comprises one or more 2\u2032-o-methyl modifications that inhibit PKR andor TLR activation.
128. The signal-activatable polynucleotide construct of claim 123, wherein the signal activatable construct is in a configuration such that at 37\xb0 C. in physiological conditions, a form of the signal activatable construct in absence of the signal polynucleotide is at least about 5 kcalmole, lower in free energy than a form of said signal activatable construct in presence of the signal polynucleotide.
129. The signal-activatable polynucleotide construct of claim 123, comprising two or more single-stranded polynucleotides.
130. The signal-activatable polynucleotide construct of claim 129, wherein nucleotides with chemical modifications, if any, are largely present on one or more said single-stranded polynucleotides.
131. The signal-activatable polynucleotide construct of claim 129, wherein the signal-activatable polynucleotide is not activated in the presence of the signal polynucleotide when one or more said single-stranded polynucleotides are removed from the construct.
132. The signal-activatable polynucleotide construct of claim 129, wherein two or more of said single-stranded polynucleotides are covalently linked by a linker moiety (such as PEG) or a bond other than canonical polynucleotide linkage.
133. The signal-activatable polynucleotide construct of claim 123, configured to have two or more signal polynucleotides bind simultaneously or sequentially to different portions of said signal detection region.
134. The signal-activatable polynucleotide construct of claim 123, wherein the targeting domain comprises a guide sequence and a sense sequence forming a duplex region of no more than 19 base pairs in length.
135. The signal-activatable polynucleotide construct of claim 134, wherein the duplex region comprises one or more chemical modifications that confer resistance to nuclease degradation.
136. The signal-activatable polynucleotide construct of claim 134, wherein in the absence of the signal polynucleotide, the guide sequence and the sense sequence form a double-stranded region comprising one or more chemical modifications that inhibits Dicer cleavage andor productive RISC incorporation.
137. The signal-activatable polynucleotide construct of claim 134, wherein the guide sequence is substantially complementary to a transcript of a target gene.
138. The signal-activatable polynucleotide construct of claim 123, wherein the targeting domain is configured to interfere with a target intracellular process of the cells through RNAi in presence of the signal polynucleotide.
139. The signal-activatable polynucleotide construct of claim 123, wherein the targeting domain comprises siRNA, microRNA, andor additional duplex structure is suitable to be used in connection with RNA interfering.
140. The signal-activatable polynucleotide construct of claim 123, wherein in the absence of the signal polynucleotide, generation of the siRNA or miRNA andor productive incorporation of said siRNA or miRNA into RISC is inhibited by at least about 2-fold, 5-fold, 10-fold, or 20-fold or more.
141. A method to inhibit expression of a target gene, comprising providing an effective amount of the signal-activated polynucleotide construct of claim 123 and the said signal polynucleotide.
142. The method of claim 141, wherein said target gene is within a cell.
143. The method of claim 142, wherein the cell is contacted with the signal-activated polynucleotide construct in vitro.
144. The method of claim 142, wherein the cell is that of a human, a non-human primate, a non-primate mammal, a rodent, a livestock animal, a bird, an insect, a fly, a worm, or a plant.
145. A pharmaceutical composition comprising an effective amount of one or more of the signal-activated polynucleotide construct of claim 123 and a pharmaceutically acceptable amount of excipients, carriers, or diluents.
146. A vector encoding the signal-activated polynucleotide construct of claim 123.
147. A cell comprising the signal-activated polynucleotide construct of claim 123.