Described is a liquid composition containing naked RNA, such as mRNA encoding a polypeptide, for use in the treatment or prevention of ligament or tendon lesions as well as a method for treating ligament or tendon lesions comprising the administration of a liquid composition containing naked RNA, such as mRNA encoding a polypeptide, which is beneficial in the process of healing the ligament or tendon lesions.

The present invention relates to innovative means of DNA sequence editing involving in-situ cut-and-paste (iCAP) or alternatively cut-and-paste in-situ (CAPi). Thus, in various embodiments described herein, the methods of the invention relate to methods of generating paired-end nucleic acid fragment sharing common linker nucleic acid sequences using a nicking endonuclease, a T7 endonuclease, a restriction enzyme or a transposase, methods of analyzing the nucleotides sequences from the linked-paired-end sequenced fragments and methods of de novo whole genome mapping.

Provided is a system for regulating expression of a gene of interest in a target cell, including a recombinant first RNA molecule with (i) a coding sequence for a translation-suppressor protein and (ii) a first microRNA (miR) recognition element in its 3 UTR, wherein the first miR recognition element recognizes a first miR and binding of a first miR to the first miR recognition element reduces translation of the translation suppressor, and a recombinant second RNA molecule, with (i) a coding sequence for the gene of interest, (ii) a recognition sequence for the translation-suppressor, wherein binding of the translation-suppressor to the recognition sequence for the translation-suppressor reduces translation of the gene of interest, and, optionally, (iii) a second miR recognition element in its 3 UTR, wherein the second miR recognition element recognizes one or more second miR and binding of one or more of the one or more second miR to the second miR recognition element reduces translation of the gene of interest. Also provided are methods of using the system.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.

The invention refers to genetic engineering and can be used in biotechnology, medicine, and agriculture for the manufacture of gene therapy products. A gene therapy DNA vector based on the VTvaf17 gene therapy DNA vector is proposed that carries a target gene selected from the group of SHH, CTNNB1, NOG, WNT7A genes for the treatment of diseases characterized by impaired tissue regeneration, wound healing, growth, pigmentation and hair coloring, formation and maturation of hair follicles, processes of differentiation and growth of cells, leading to a decrease in the activity of hair follicles, including with allopecia, autoimmune diseases, hereditary and acquired pathological conditions thawing, and for accelerated healing of wounds, restoration of the hairline and the prevention and inhibition of alopecia. Moreover, the gene therapy DNA vector VTvaf17-SHH, or VTvaf 17 -CTNNB 1, or VTvaf17-NOG, or VTvaf17-WNT7A has the nucleotide sequence of SEQ ID No. 1 or SEQ ID No. 2 or SEQ ID No. 3 or SEQ ID No. 4, respectively. Also provided are a method of producing said vector, the use of a vector, a strain of Escherichia coli carrying said vector, as well as a method of industrial production of said vector.

An injector configured to inject a solution containing a biomolecule and a gas that is predetermined into an injection target without using an injection needle, the injector including a storage portion configured to store the solution containing the biomolecule and the gas, a nozzle portion communicating with the storage portion, the nozzle portion including an ejection port configured to eject the solution containing the biomolecule and the gas toward the injection target, and a pressurization portion configured to pressurize the solution containing the biomolecule and the gas that are stored in the storage portion during an operation and to eject the solution containing the biomolecule and the gas from the ejection port toward the injection target.

Compositions that specifically cleave target sequences in Flavivirus, for example Zika virus include a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) associated endonuclease, a guide RNA sequence complementary to a target sequence in a Zika virus and an anti-viral agent. These compositions are administered to a subject for treating an infection or at risk for contracting a Zika virus infection.

Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models.

Methods and compositions are provided for activating transcription in a mammalian cell.

The present disclosure provides codon optimized Factor VIII sequences, vectors, and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides. The present disclosure also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor VIII nucleic acid sequence or the polypeptide encoded thereby.