Aspects of the disclosure relate to compositions and methods for treating certain diseases associated with the presence of one or more premature stop codons in a gene, for example dominantly inherited diseases or recessively inherited diseases. In some embodiments, compositions comprise a vector (e.g., a viral vector, such as an rAAV vector) encoding one or more synthetic suppressor transfer RNAs (tRNAs) configured to read-through certain stop codons (e.g., premature stop codons). In some embodiments, the disclosure relates to methods for treating Hurler syndrome comprising administering such vectors to a subject.
In some aspects, the disclosure relates to compositions and methods for modulating (e.g., increasing and/or decreasing) bone mass in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that promote (e.g., increase) or inhibit (e.g., decrease) activity, differentiation, or function of certain types of bone cells, for example osteoblasts, osteoclasts, osteocytes, etc. In some embodiments, the isolated nucleic acids and vectors described by the disclosure are useful for treating disorders and conditions associated with increased bone mass (e.g., osteopetrosis) or decreased bone mass (e.g., osteoporosis).
Compositions And Methods For Transient Delivery Of Nucleases
The disclosure in some aspects relates to recombinant adeno-associated viruses having nuclease grafted to one or more capsid proteins. In some aspects, the disclosure relates to isolated AA V capsid proteins having terminally grafted nucleases and isolated nucleic acids encoding the same. Recent approaches to delivering nucleases to cells for gene editing have focused on delivering of expression vectors engineered to express the nucleases in target cells. However, these approaches have proved to be problematic in many instances due to genotoxicity resulting from to prolonged expression of gene editing system in vivo. To prevent such off-target genotoxicity due to prolonged presence of a gene editing system, several studies explored delivery of mRNA or protein instead of delivering the gene coding for the nucleases in cell culture.
Self-Regulating Aav Vectors For Safe Expression Of Mecp2 In Rett Syndrome
- Boston MA, US Guangping GAO - Westborough MA, US Michael R. GREEN - Boylston MA, US Dan WANG - Belchertown MA, US Tessa Mercedes SIMONE - Worcester MA, US
Assignee:
University of Massachusetts - Boston MA
International Classification:
C12N 15/86 C07K 14/47
Abstract:
In some aspects, the disclosure relates to compositions and methods of engineering a transgene. In some embodiments, the disclosure provides self-regulating recombinant nucleic acids, viral vectors and pharmaceutical compositions comprising a MeCP2 transgene. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases and disorders associated with a loss of function mutation, for example Rett syndrome.
Compositions And Methods For Transient Delivery Of Nucleases
The disclosure in some aspects relates to recombinant adeno-associated viruses having nuclease grafted to one or more capsid proteins. In some aspects, the disclosure relates to isolated AAV capsid proteins having terminally grafted nucleases and isolated nucleic acids encoding the same. Recent approaches to delivering nucleases to cells for gene editing have focused on delivering of expression vectors engineered to express the nucleases in target cells. However, these approaches have proved to be problematic in many instances due to genotoxicity resulting from to prolonged expression of gene editing system in vivo. To prevent such off-target genotoxicity due to prolonged presence of a gene editing system, several studies explored delivery of mRNA or protein instead of delivering the gene coding for the nucleases in cell culture.
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Chicago Meat Authority Inc Meat Packing Plants
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