Provided herein are methods and compositions for treatment of Batten disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV 5′ inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3′ ITR.

Disclosed herein are peptide sequences capable of directing adeno-associated viruses (AAV) to target specific environments, for example the nervous system and the heart, in a subject. Also disclosed are AAVs having non-naturally occurring capsid proteins comprising the disclosed peptide sequences, and methods of using the AAVs to treat diseases.

The present invention provides a method for producing an alcohol comprising: (a) admixing a tripeptidyl peptidase, predominantly having exopeptidase activity, with a feedstock or a fraction thereof before, during or after fermentation of said feedstock or a fraction thereof; and (b) recovering an alcohol. Also provided are uses of a tripeptidyl peptidase and by-products of alcohol production obtainable by the method of the invention.

A method for the production of a hydrolysate comprising: (a) admixing at least one protein or a portion thereof with: (A) at least one endoprotease; and (B) (a′) at least one proline tolerant tripeptidyl peptidase or fermentate comprising a proline tolerant tripeptidyl peptidase predominantly having exopeptidase activity wherein said proline tolerant tripeptidyl peptidase is capable of cleaving tri-peptides from the N-terminus of peptides having: Proline at P1; and synthetic amino acids at P1; or (b′) at least one proline tolerant tripeptidyl peptidase having exopeptidase activity wherein said proline tolerant tripeptidyl peptidase is capable of cleaving tri-peptides from the N-terminus of peptides having: Proline at PV; and synthetic amino acids at PV; and (b) recovering the hydrolysate. The invention also relates to methods for producing a hydrolysate comprising the use of an endoprotease an exo-tripeptidyl peptidase of the S53 family and an aminopeptidase, to uses of a proline tolerant tripeptidyl peptidase, compositions, food and/or feed additive compositions comprising the same, as well as hydrolysates and uses of proline tolerant tripeptidyl peptidases.

Disclosed are a means to convert compounds having physiological or pharmacological activity and unable to pass through the blood-brain barrier into a form that allows them to pass through the blood-brain barrier, and compounds converted thereby. The means is an anti-human transferrin receptor antibody and the converted compounds are molecular conjugates between physiologically active protein or pharmacologically active low-molecular-weight compounds and an anti-human transferrin receptor antibody.

Provided herein are methods and compositions for treatment of Batten disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV 5′ inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3′ ITR. Also provided herein are methods of treating Batten disease comprising administering to a subject in need thereof the rAAV described herein via more than one route. Also provide herein are pharmaceutical compositions comprising the rAAV described herein and related methods of treating Batten disease.

Disclosed herein are methods for treating a primate in need of tripeptidyl peptidase 1 (TPP1), comprising (a) providing a recombinant adeno-associated virus (AAV) vector comprising a nucleic acid encoding TPP1; and (b) administering an amount of the recombinant AAV vector to the central nervous system (CNS) of the primate, wherein the TPP1 is expressed in the primate.

A method for the production of a hydrolysate comprising: (a) admixing at least one protein or a portion thereof with: (A) at least one endoprotease; and (B) (a′) at least one proline tolerant tripeptidyl peptidase or fermentate comprising a proline tolerant tripeptidyl peptidase predominantly having exopeptidase activity wherein said proline tolerant tripeptidyl peptidase is capable of cleaving tri-peptides from the N-terminus of peptides having: Proline at P1; and synthetic amino acids at P1; or (b′) at least one proline tolerant tripeptidyl peptidase having exopeptidase activity wherein said proline tolerant tripeptidyl peptidase is capable of cleaving tri-peptides from the N-terminus of peptides having: Proline at PV; and synthetic amino acids at PV; and (b) recovering the hydrolysate. The invention also relates to methods for producing a hydrolysate comprising the use of an endoprotease an exo-tripeptidyl peptidase of the S53 family and an aminopeptidase, to uses of a proline tolerant tripeptidyl peptidase, compositions, food and/or feed additive compositions comprising the same, as well as hydrolysates and uses of proline tolerant tripeptidyl peptidases.

Provided herein are methods for the treatment of lysosomal storage disease comprising administration of genes encoding for a lysosomal enzyme and a pharmaceutical agent. Combining gene therapy with pharmaceutical compositions by co-administration not only further enhances the effects of each individual therapy, but also provides a multi-faceted approach to treatment because of the varying mechanism of action of each individual composition.

Formulations comprising recombinant human tripeptidyl peptidase-1 (rhTPP1) for intrathecal, intracerebroventricular, or intraocular administration, and kits comprising the same, are disclosed. Methods of using rhTPP1 in the prevention and treatment of symptoms of Neuronal Ceroid Lipofuscinosis (CLN2) disease are also disclosed. The formulations and methods are effective in halting the progression of CLN2 disease and may be used to treat subjects having CLN2 or a family history of CLN2.