Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Compositions and methods for mitochondria genome editing are provided. Also provided are methods for treating mitochondrial disorders by the disclosed compositions.

The present invention provides an amphiphilic poly(amino acid) for nucleic acid delivery, which is represented by the following formula (1): where: R.sup.1 represents a hydroxy group, an oxybenzyl group, an —O—R.sup.1a group, or an —NH—R.sup.1b group, where R.sup.1a and R.sup.1b each independently represent an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms; R.sup.2 represents a hydrogen atom, an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted, linear or branched alkylcarbonyl group having 1 to 24 carbon atoms; R.sup.3a, R.sup.3b, R.sup.4a, and R.sup.4b each independently represent a methylene group or an ethylene group; R.sup.5a and R.sup.5b each independently represent —O— or —NH—; R.sup.6a and R.sup.6b each independently represent an unsubstituted or substituted aliphatic hydrocarbon group having 7 to 12 carbon atoms that may contain an alicycle; R.sup.7a and R.sup.7b are each independently selected from groups identical to or different from each other in the group consisting of the following groups: —NH—(CH.sub.2).sub.p1—[NH—(CH.sub.2).sub.q1—].sub.r1NH.sub.2 (i); —NH—(CH.sub.2).sub.p2—N[—(CH.sub.2).sub.q2—NH.sub.2].sub.2 (ii); —NH—(CH.sub.2).sub.p3—N{[—(CH.sub.2).sub.q3—NH.sub.2][—(CH.sub.2).sub.q4—NH—].sub.r2H} (iii); and —NH—(CH.sub.2).sub.p4—N{—(CH.sub.2).sub.q5—N[—(CH.sub.2).sub.q6—NH.sub.2].sub.2}.sub.2 (iv), where p1 to p4, q1 to q6, and r1 and r2 each independently represent an integer of from 1 to 5; R.sup.8 represents a side chain of an amino acid selected from the group consisting of ornithine, lysine, homolysine, arginine, homoarginine, and histidine; m represents an integer of 9 or more; n represents an integer of from 0 to m; x represents an integer of from 2 to 300; y represents an integer of from 0 to x; and z represents an integer of from 0 to x, provided that a relationship of y+z≤x and a relationship of 11≤m+x≤400 are satisfied, and repeating units in the formula (1) may be randomly present.

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A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

Methods and systems are provided for transfecting cells using real-time, continuous transfection of cells. In some aspects, the methods can be applied for the continuous production of non-viral vector nucleic acid complexes. The systems and methods include a passive mixing fluidic module with at least two inlets, a plurality of mixing elements, and an outlet to provide a continuous flow of transfection complexes to a cell reactor. The transfection agent and nucleic acid are passively mixed and then provided to cells in a continuous flow of cell medium. In some aspects, the flow of cell medium perfusing through the cell reactor recirculates. The system and the methods of the present disclosure provide for highly reproducible and scalable transfection with a low coefficient of variation.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

A method for modulating a methylation/demethylation state of a nucleic acid, more specifically, a method for site-removing one or more methylated bases from a genome guided by a sgRNA sequence in a cell.