Antibody-mediated immunocontraception
The present disclosure generally relates to methods and compositions for contraception. In some embodiments, vector based approaches for contraception are provided.
1. A recombinant genetic construct comprising an antibody gene that encodes an antibody or a fragment thereof that binds to a protein, a peptide, or a small molecule specific to reproductive function, wherein the recombinant genetic construct is configured to be delivered and expressed in an animal subject, wherein the antibody comprises an amino acid sequence that is at least 90% identical to that in SEQ ID NOs: 10, 12, 13, or 14.
2. The recombinant genetic construct of claim 1 , wherein the antibody inhibits a protein specific to reproductive function.
3. The recombinant genetic construct of claim 1 , wherein the protein specific to reproductive function is one that, when bound by the antibody, causes sterility.
4. The recombinant genetic construct of claim 1 , wherein the protein is a reproductive hormone, a protein component of the egg zona pellucida, or a protein component of the sperm plasma membrane.
5. The recombinant genetic construct of claim 1 , wherein the amino acid sequence is at least 95% identical to that in SEQ ID NOs: 10, 12, 13, or 14.
6. The recombinant genetic construct of claim 1 , wherein the amino acid sequence is at least 99% identical to that in SEQ ID NOs: 10, 12, 13, or 14.
7. The recombinant genetic construct of claim 1 , wherein the antibody comprises 6 CDRs, wherein the 6 CDRs are 6 CDRs are encoded by SEQ ID NOs:10 and 12, or 13 and 14.
8. The recombinant genetic construct of claim 1 , wherein the antibody comprises an amino acid sequence SEQ ID NOs: 10, 12, 13, or 14.
9. The recombinant genetic construct of claim 1 , wherein the antibody comprises SEQ ID NOs:
a) 10 and 12, or
b) 13 and 14.
10. The recombinant genetic construct of claim 1 , wherein the antibody comprises an amino acid sequence that is at least 90% identical to that in SEQ ID NO: 12.
11. The recombinant genetic construct of claim 1 , wherein the antibody comprises an amino acid sequence that is at least 90% identical to that in SEQ ID NO: 13.
12. The recombinant genetic construct of claim 1 , wherein the antibody or fragment thereof comprises an amino acid modification that enhances or suppresses an effector function of the encoded antibody or fragment.
13. The recombinant genetic construct of claim 1 , comprising an antibody expression cassette comprising a tissue specific promoter, a regulatory element, and one or more microRNA target sites.
14. The recombinant genetic construct of claim 13 , wherein the regulatory element is a 5′ untranslated region (5′ UTR) or a 3′ untranslated region (3′ UTR).
15. The recombinant genetic construct of claim 1 , incorporated into a transfection vehicle selected from the group consisting of an adeno-associated virus (AAV), a lentivirus, a DNA-containing nanoparticle, a liposome-DNA mixture, and a peptide-DNA mixture.
16. A contraceptive composition comprising the recombinant genetic construct of claim 1 .
17. The contraceptive composition of claim 16 , configured to be delivered to an animal through intramuscular injection, subcutaneous injection, intravenous injection, intraperitoneal injection, oral delivery, electroporation through the skin, sonication, or nasal inhalation.
18. A pharmaceutical composition comprising:
the recombinant genetic construct of claim 1 ; and
a pharmaceutically acceptable carrier, wherein the recombinant genetic construct is present in at least 1 ug/ml, and wherein the pharmaceutically acceptable carrier can be combined with a nucleic acid.
19. The recombinant genetic construct of claim 1 , wherein the antibody comprises 3 CDRs, wherein the 3 CDRs are 3 CDRs are encoded by SEQ ID NO: 28.
20. The recombinant genetic construct of claim 1 , wherein the antibody comprises 3 CDRs, wherein the 3 CDRs are 3 CDRs are encoded by SEQ ID NO: 35.
21. The recombinant genetic construct of claim 1 , wherein the antibody comprises an amino acid sequence that is at least 90% identical to that in SEQ ID NO: 14.