Cytidine nucleoside analogues of Formula I, wherein the variables are as described herein, in combination with uridine nucleoside analogues of Formula II, wherein the variables are as described herein,

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produce a synergistic effect on the inhibition of HCV polymerase.

Cytidine nucleoside analogues of Formula I, wherein the variables are as described herein, in combination with uridine nucleoside analogues of Formula II, wherein the variables are as described herein,

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produce a synergistic effect on the inhibition of HCV polymerase.

This disclosure relates to treatment of lysosomal storage disorders, such as Fabry disease or Gaucher disease, with a combination treatment containing (i) an mRNA encoding a lysosomal enzyme deficient in the lysosomal storage disorder, and (ii) a compound that is a glucosylceramide synthase inhibitor or a pharmacological chaperone of the lysosomal enzyme. mRNAs for use in the invention, when administered in vivo, encode the enzyme that is deficient in the lysosomal storage disorder, functional fragments thereof (e.g., those comprising the catalytic domain), or fusion proteins containing the enzyme that is deficient in the lysosomal storage disorder. mRNA therapies can be used to increase and/or restore deficient levels of a lysosomal enzyme's expression and/or activity in subjects.

This disclosure relates to treatment of lysosomal storage disorders, such as Fabry disease or Gaucher disease, with a combination treatment containing (i) an mRNA encoding a lysosomal enzyme deficient in the lysosomal storage disorder, and (ii) a compound that is a glucosylceramide synthase inhibitor or a pharmacological chaperone of the lysosomal enzyme. mRNAs for use in the invention, when administered in vivo, encode the enzyme that is deficient in the lysosomal storage disorder, functional fragments thereof (e.g., those comprising the catalytic domain), or fusion proteins containing the enzyme that is deficient in the lysosomal storage disorder. mRNA therapies can be used to increase and/or restore deficient levels of a lysosomal enzyme's expression and/or activity in subjects.

A composition of matter and method of treating HIV with mesenchymal stem cells (MSC) is disclosed. Specifically, MSCs are transduced with vectors incorporating an anti-viral fusion inhibitor, such as a C46-derived peptide or neutralizing antibody. The transduced MSCs are capable of expression the inhibitor and preventing HIV virus-cell fusion.

A composition of matter and method of treating HIV with mesenchymal stem cells (MSC) is disclosed. Specifically, MSCs are transduced with vectors incorporating an anti-viral fusion inhibitor, such as a C46-derived peptide or neutralizing antibody. The transduced MSCs are capable of expression the inhibitor and preventing HIV virus-cell fusion.

A composition of matter and method of treating HIV with mesenchymal stem cells (MSC) is disclosed. Specifically, MSCs are transduced with vectors incorporating an anti-viral fusion inhibitor, such as a C46-derived peptide or neutralizing antibody. The transduced MSCs are capable of expression the inhibitor and preventing HIV virus-cell fusion.

The invention provides therapeutic combinations and therapeutic methods that are useful for treating Hepatitis B and Hepatitis D.

The invention provides therapeutic combinations and therapeutic methods that are useful for treating Hepatitis B and Hepatitis D.

The present application relates to methods for treating conditions characterized by reduced cerebral blood flow that include selecting a subject having a condition characterized by reduced cerebral blood flow. A therapeutic agent that increases the levels of PIP.sub.2 is administered under conditions effective to treat the condition in the subject. Also disclosed are methods for treating CADASIL as well as methods for restoring cerebral blood flow and functional hyperemia.