MCD BIO CM156 Lecture Notes - Lecture 22: Severe Combined Immunodeficiency, Enzyme Replacement Therapy, Viral Vector
17 Mar 2020
School
Course
Professor
Document Summary
Hematopoietic stem cells (hsc) produce all of the blood cells. Gene addition - use viral vector or non-viral delivery method to add new genetic material to cells (permanent or not). Scid is the most severe human primary immune deficiency, with absent t and b (and sometimes nk) cell function, due to defects in any of >20 genes. Ada-deficiency is cause of 10-15% of human scid. Ada-deficient scid patients have profound panlymphopenia (t-,b-,nk-) from accumulated toxic adenine metabolites. Ada scid is the first genetic form of human scid where the biochemical and genetic bases were determined. Therapeutic options include: allogeneic hsct (msd, mud, haplo, enzyme replacement therapy (ert) with peg-ada (makes blood last longer in the stream, autologous hsct with gene therapy. Absent ada isozymes observed when typing potential scid family donors (1972). Efs-ada lentiviral vector integration site 18 mo after gt. Comments: is analysis by (nr)lam pcr showed a total of 8634 different unique mappable is.
