Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

Abstract: The present invention relates to an additized blended fuel composition comprising of 97 to 50 weight % of liquified petroleum gas (LPG); 3 to 50 weight % of dimethyl ether (DME); and a nanocatalyst. More particularly, the present invention relates to an improvement in the combustion efficiency of the DME blended LPG fuel by using catalytic amount of the nano-catalyst, when introduced in ppm level enhances the combustion properties, thereby increasing the flame temperature and reducing the consumption of fuel gas mixture.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Abstract: The disclosure features compositions or systems and uses thereof, comprising a first polynucleotide encoding a target molecule, optionally a second polynucleotide encoding an effector, repressor, or endonuclease molecule; optionally a recognition or cleavage site in the first or second polynucleotide, and optionally a repressor/effector binding site in the first polynucleotide. The compositions or systems of the present disclosure can increase the level and/or activity of the target molecule in desired cells and/or microenvironments while suppressing the level and/or activity of the target molecule in off-target cells and/or microenvironments.

Abstract: This disclosure relates to mRNA therapy for the treatment of methylmalonic acidemia (MMA). mRNAs for use in the invention, when administered in vivo, encode methylmalonyl-CoA mutase (MUT). mRNA therapies of the disclosure increase and/or restore deficient levels of MUT expression and/or activity in subjects.

Abstract: This disclosure relates to messenger RNA (mRNA) therapy for the treatment of methylmalonic acidemia. mRNAs for use in the invention, when administered in vivo, encode methylmalonyl-CoA mutase. mRNA therapies of the disclosure increase and/or restore deficient levels of MUT expression and/or activity in subjects.

Abstract: This disclosure relates to mRNA therapy for the treatment of ornithine transcarbamylase deficiency (OTCD). mRNAs for use in the invention, when administered in vivo, encode human ornithine transcarbamylase (OTC). mRNA therapies of the disclosure increase and/or restore deficient levels of OTC expression and/or activity in subjects. mRNA therapies of the disclosure further decrease levels of toxic ammonia associated with deficient OTC activity in subjects.

Abstract: The present invention relates to an anti-viral nanoformulation suitable for diverse surface application in form of hydrogel based nanoemulsion, or an aerosol spray. The present invention discloses incorporation of nanomaterials such as functionalized carbon quantum dots (F-CQDs), copper nanoparticles (CuNPs) or silver nanoparticles (AgNPs) into the hydrogel (HG) scaffold to act as chemical barrier and anti-viral agent against SARS-CoV-2 or Escherichia coli: phage MS2. The nanoformulation is coated on personal protective equipment's (PPE) and different surfaces such as glass, steel and plastic to control viral infection including corona virus infection.

Abstract: The present invention relates to an additized blended fuel composition comprising of 97 to 50 weight % of liquified petroleum gas (LPG); 3 to 50 weight % of dimethyl ether (DME); and a nanocatalyst. More particularly, the present invention relates to an improvement in the combustion efficiency of the DME blended LPG fuel by using catalytic amount of the nano-catalyst, when introduced in ppm level enhances the combustion properties, thereby increasing the flame temperature and reducing the consumption of fuel gas mixture.

Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Abstract: The disclosure features a polynucleotide encoding a polypeptide, which polynucleotide comprises: a 5?UTR described herein; a coding region comprising a payload and a stop element described herein; and a 3?UTR described herein, and LNP compositions comprising the same. The polynucleotides and/or LNP compositions of the present disclosure can: increase the level and/or activity of the payload by increasing the half-life and/or duration of expression of the polynucleotide encoding the payload or of the payload polypeptide. Also disclosed herein are methods of treating a disease or disorder in a subject using the LNP compositions of the present disclosure.

Abstract: The disclosure features LNP compositions and systems comprising a therapeutic payload or prophylactic payload, a binding element, a tether molecule and/or an effector molecule and uses thereof. The LNP compositions or systems of the present disclosure comprise: (a) a first polynucleotide (e.g., mRNA) comprising: (1) a sequence encoding a therapeutic payload or prophylactic payload, and (2) a binding element; and (b) a second polynucleotide (e.g., mRNA) comprising a sequence encoding: (1) an effector molecule, and/or (2) a polypeptide that recognizes the binding element (a tether molecule). Such compositions or systems can: increase the level and/or activity of the therapeutic payload or prophylactic payload, e.g., increase the level, stability and/or activity of the mRNA encoding the therapeutic payload or prophylactic payload. Also disclosed herein are methods of treating a disorder, or for modulating an immune response in a subject using the disclosed LNP compositions or systems.

Abstract: The disclosure features mRNAs engineered with one or more microRNA binding sites targeted by a microRNA(s) that are differentially expressed in a target immune cell relative to a plurality of non-target immune cells. The disclosure also features methods of using the same, for example, for selectively degrading the mRNA in the target immune cell relative to the plurality of non-target immune cells.

Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

Abstract: The present invention includes the discovery of a strain of Mycobacterium comprising an expression vector encoding a di-adenylate cyclase enzyme. The Mycobacterium is selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, or a combination thereof and the preferred strain of Mycobacterium is BCG. The preferred expression vector is a mycobacterial expression vector including an hsp60 promoter and a DNA sequence of diadenylate cyclase (disA), or a functional part thereof. The strains of Mycobacterium are used in therapeutic applications including tuberculosis and cancer.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide desirable regulation of mRNA localization, stability, and/or translation to yield increased mRNA expression and activity of an encoded polypeptide.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Abstract: The present invention relates to an anti-viral nanoformulation suitable for diverse surface application in form of hydrogel based nanoemulsion, or an aerosol spray. The present invention discloses incorporation of nanomaterials such as functionalized carbon quantum dots (F-CQDs), copper nanoparticles (CuNPs) or silver nanoparticles (AgNPs) into the hydrogel (HG) scaffold to act as chemical barrier and anti-viral agent against SARS-CoV-2 or Escherichia coli: phage MS2. The nanoformulation is coated on personal protective equipment's (PPE) and different surfaces such as glass, steel and plastic to control viral infection including corona virus infection.

Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.