Table 1. Comparison of the advantages and disadvantages of HSCT to future possible DNA- and RNA-based therapeutic approaches for DBA.

Present Therapeutic Strategies		Advantages	Disadvantages	Refs.
Hematopoietic stem cell transplantation		• One treatment is resolutive, if successful • High rate of success for HLA-matched donors • Feasible without knowing the causative mutation	• Risk of GvHD • Adverse effects due to preconditioning • Risk of unknown mutations in silent carriers • Immunosuppressive therapy	[1, 30, 31]
Future therapeutic strategies		Advantages	Disadvantages	Refs.
DNA-based	Ex vivo gene addition in HSCs	• One treatment is resolutive, if successful • No need for a donor; no need for prolonged immunosuppressive therapy; no GvHD occurrence • Reduced or absent preconditioning	• The causative mutation must be known • Off targets effects • Risk of insertional mutagenesis	[54, 57-59, 61]
	Ex vivo gene addition in iPSCs	• One treatment is resolutive, if successful • No need for a donor; no need for prolonged immunosuppressive therapy; no GvHD occurrence • Unlimited source of autologous cells • Cell genome can be studied before reinfusion • Reduced or absent preconditioning	• The causative mutation must be known • Very low reprogramming efficiency • Risks connected to reprogramming procedure • Off targets effects • Risk of insertional mutagenesis • Risk of somatic mutations in the cells of origin	[64, 65, 68, 69]
	In vivo gene addition	• One treatment is resolutive, if successful • No need for a donor; no need for prolonged immunosuppressive therapy; no GvHD occurrence • No preconditioning	• The causative mutation must be known • Off targets effects • Risk of insertional mutagenesis • Possible immune response against the vector • Lack of data for the application of this technology to RP genes	[71-73]
	Gene editing	• One treatment is resolutive, if successful • No need for a donor; no need for prolonged immunosuppressive therapy; no GvHD occurrence • No preconditioning • Gene expression is under the regulation of endogenous mechanisms	• The causative mutation must be known • Off targets effects • Lack of data for the application of this technology to RP genes	[74, 82]
RNA-based	SMaRT SINEUPs saRNAs	• No need for a donor; no need for prolonged immunosuppressive therapy; no GvHD occurrence • No preconditioning • Theoretically very specific • The expression of the deficient gene is increased to a physiological level	• Chronic administrations are needed • The causative mutation must be known • Off targets effects • Lack of data for the application of these technologies to RP genes	[88, 90, 92-94, 96, 97]