A personalized method of inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus, by determining a nucleic acid sequence of the HIV-1 proviral DNA harbored by a subject, designing two or more different multiplex guide RNAs (gRNAs) complementary to the HIV-1 proviral DNA sequences in the subject, administering to the subject a therapeutically effective amount of a composition comprising a CRISPR-associated endonuclease, and the two or more different multiplex gRNAs, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, and eradicating the HIV-1 proviral DNA from the host cell.

A method of preventing transmission of a retrovirus from a mother to her offspring, by administering to the mother a therapeutically effective amount of a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and the two or more different multiplex gRNAs, wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, eradicating the HIV-1 proviral DNA from the host cell, and preventing transmission of the proviral DNA to the offspring.

A method of treating a subject having or at risk for having an HIV-1 virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a CRISPR-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, eradicating the HIV-1 proviral DNA from the host cell, and completely resolving the symptoms of HIV-1, decreasing the severity of the symptoms of HIV-1, or slowing HIV-1's progression.

A method of immunizing a subject at risk of HIV-1 virus infection, by administering to the subject a prophylactically effective amount of a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, eradicating the HIV-1 proviral DNA from the host cell, and preventing HIV-1 virus infection in the subject.

A method of treating a subject having or at risk for having an HIV-1 virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, eradicating the HIV-1 proviral DNA from the host cell, and causing neither genotoxicity nor off-target editing to the host.

A method of treating a subject having or at risk for having a virus infection, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the 5- to 3-LTRs of the sequence in the virus, and completely excising a fragment of greater than 9000-bp of integrated proviral DNA that spanned from its 5- to 3-LTRs. A method of treating a subject having or at risk for having a genetic caused disease, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the sequence of the subjects DNA greater than 9000-bp that is chromosomally integrated and causes the genetic caused disease, and excising the chromosomally integrated sequence.

Methods of inactivating a proviral DNA genome or a DNA genome integrated into the genome of a host cell latently infected with a retrovirus, by treating the host cell with a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of the proviral DNA that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire proviral genome of the proviral DNA, and eradicating the proviral DNA from the host cell.

A method of treating a subject having a retroviral infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5- to 3-LTRs of the sequence in the retrovirus, and eradicating the retroviral infection. A method of immunizing a subject at risk of retroviral infection, by administering a prophylactically effective amount of a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of a retrovirus to the subject, and preventing retroviral infection in the subject.

A method of treating a subject having or at risk for having a virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5- to 3-LTRs of the sequence in the virus, and completely resolving the symptoms of a disease, decreasing the severity of the symptoms of the disease, or slowing the disease's progression.

The present invention relates to the seminal discovery of methods of using recombinant galectin proteins to reverse HIV latency. Specifically, the present invention relates to the use of recombinant galectin-9 (rGal-9) to reactivate latent HIV, wherein the HIV is hypermutated rendering the virus replication incompetent. Further, rGal-9 induces the expression of APOBEC3 cytidine deaminases and NFkB pathway components and decreases histone deacetylase (HDAC) expression.