Methods and composition for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed.

The invention relates to a bonding and forming device for an inner box of a paper box and surface paper. The bonding and forming device comprises a stand, a lifting platform, a paper box inner support member, a flanging pressing plate, an ejector pin, a left hairbrush, a right hairbrush, a first pushing part, a front hairbrush, a rear hairbrush and a second pushing part and also comprises a driving device, a first control device a second control device, a third control device, a fourth control device and a fifth control device, wherein the driving device is used for driving the ejector pin to rise or fall; the first control device is used for controlling the paper box inner support member to rise or fall; the second control device is used for controlling the left hairbrush and the right hairbrush to stretch; the third control device is used for controlling the first pushing part to stretch; the fourth control device is used for controlling the front hairbrush and the rear hairbrush to stretch; the fifth control device is used for controlling the second pushing part to stretch; an inhibiting device is arranged between the first control device and the driving device; and the paper box inner support member and the flanging pressing plate are respectively provided with a through hole for the ejector pin to pass through. By adopting the technical scheme, according to the bonding and forming device for the inner box of the paper box and the surface paper, provided by the invention, the inner box and other surfaces of the surface paper can be automatically bonded to be formed after a bottom plate of the inner box and the bottom surface of the surface paper are bonded. The degree of automation is high and the production efficiency is high.

The present disclosure provides improved multiplex genome editing compositions and methods. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

A polynucleotide comprising a nucleotide sequence encoding an epidermal growth factor receptor (EGFR) extracellular epitope operably linked to: (a) a NGFR or GMS SFR alpha signal peptide; (b) a EGFR or NGFR transmembrane domain; and/or (c) a NGFR or EGFR cytosplasmic tail.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides encoding AADC for the treatment of Parkinson's Disease.

Methods and composition for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed.

The present invention relates to an mRNA sequence, comprising a coding region, encoding at least one antigenic peptide or protein derived from the glycoprotein (GP) and/or the matrix protein 40 (VP40) and/or the nucleoprotein (NP) of a virus of the genus Ebolavirus or Marburgvirus or a fragment, variant or derivative thereof. Additionally, the present invention relates to a composition comprising a plurality of mRNA sequences comprising a coding region, encoding at least one antigenic peptide or protein derived from the glycoprotein (GP) and/or the matrix protein 40 (VP40) and/or the nucleoprotein (NP) of a virus of the genus Ebolavirus or Marburgvirus or a fragment, variant or derivative thereof. Furthermore it also discloses the use of the mRNA sequence or the composition comprising a plurality of mRNA sequences for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the prophylaxis or treatment of Ebolavirus or Marburgvirus infections. The present invention further describes a method of treatment or prophylaxis of Ebolavirus or Marburgvirus infections using the mRNA sequence.

The present invention relates to a covalently closed circular recombinant DNA molecule comprising an origin of replication and an insert comprising a homopolymeric region, wherein the homopolymeric region is located at a distance of least 500 bp from the origin of replication in the direction of replication and/or wherein the insert comprising a homopolymeric region is oriented so that the direction of transcription of the insert is the same as the direction of replication of the origin of replication. The invention further relates to the use of the covalently closed circular recombinant DNA molecule for increasing the yield and/or shortening the fermentation time during fermentation.

Provided is a recombinant adeno-associated virus (rAAV) having an AAV capsid and a vector genome which comprises a nucleic acid sequence encoding a functional CDKL5 (hCDKLK5). Also provided are a production system useful for producing the rAAV, a pharmaceutical composition comprising the rAAV, and a method of treating a subject having CDD, or ameliorating symptoms of CDD, or delaying progression of CDD via administrating an effective amount of the rAAV to a subject in need thereof.

The present invention provides, among other things, multimeric coding nucleic acids that exhibit superior stability for in vivo and in vitro use. In some embodiments, a multimeric coding nucleic acid (MCNA) comprises two or more encoding polynucleotides linked via 3′ ends such that the multimeric coding nucleic acid compound comprises two or more 5′ ends.